Preface
Contents
Contributors
1: Essentials of the Immune Response and Immunophenotyping
List of Frequently Asked Questions
1. What are the basic divisions of the immune response?
2. How does the immune system distinguish self from non-self?
3. How does the acquired immune system respond to antigens?
4. What are pathologic immune reactions?
5. How do the cellular components of the immune system develop and how are they distributed in the body?
6. What is an “immunophenotype”? How is it determined in hematopathology?
7. What is the immunophenotype of myeloid and lymphoid cells at various stages in maturation?
8. What is the role of immunophenotyping in the classification of acute leukemias? (See also Chap. 21)
9. How are the compartments of the immune system and normal lymphoid architecture related to the classification of lymphomas?
10. How can immunohistochemistry be used optimally for diagnosis and differential diagnosis in hematopathology?
11. How can a panel of antibodies be used to differentiate among the common B-cell neoplasms?
12. How can a panel of antibodies be used to differentiate among the common T-cell neoplasms?
13. How can a basic panel of antibodies be used to distinguish common neoplasms from reactive lymphoid hyperplasia?
14. How does the immunophenotype of normal thymus differ from T-lymphoblastic leukemia/lymphoma?
15. How does the immunophenotype of normal B-cell precursors (hematogones) differ from B-lymphoblastic leukemia/lymphoma?
16. Which antibodies are most useful in the analysis of myeloid neoplasms?
17. How are antigens expressed by various lymphoid and myeloid malignancies being targeted by immune-based therapies?
References
2: Molecular Genetics and Cell Biology for Hematopathology
List of Frequently Asked Questions
1. What is molecular genetics, and why is understanding molecular genetics and cellular biology critical for the pathological diagnosis of lymph node and bone marrow?
2. Why are some molecular features (like PML-RARA) used to classify a disease, while others (like FLT3-ITD and TP53) are not?
3. What is a clonal process, and how is it related to a neoplastic process?
4. What is clonal evolution and how is it related to disease progression?
5. With fluorescence in situ hybridization (FISH) and all the molecular methods including next-generation sequencing (NGS) available in the clinical laboratories, why is chromosome analysis (conventional karyotyping) still necessary?
6. What are the advantages and disadvantages of fluorescence in situ hybridization (FISH) test?
7. If we have conventional karyotyping and FISH test available, is microarray test still useful?
8. What are the typical applications of polymerase chain reaction (PCR)- based tests in the clinical laboratory?
9. What are the indications of conventional sequencing (first- generation Sanger sequencing and pyrosequencing) in the lymph node and bone marrow pathology?
10. Testing for IGH/BCL2 can be performed by a PCR- based method or a FISH method. Are there any differences in the indications of these two methods?
11. What are the indications of FISH test for BCR-ABL1 fusion when there is a quantitative PCR test available?
12. How do I choose a method to test for PML-RARA when blood smear review suspects acute promyelocytic leukemia (APL)?
13. What are the principles of B- cell (immunoglobulin gene) and T- cell (T- cell receptor gene) clonality tests?
14. What are the indications of B- cell (immunoglobulin gene) and T- cell (T- cell receptor gene) clonality tests, and what are the pitfalls in interpreting the test results?
15. Can I use clonal immunoglobulin (Ig) or T- cell receptor (TCR) gene rearrangement as an evidence to prove the B- cell or T- cell lineage of lymphoma?
16. What are the key concepts required to understand the clinical next- generation sequencing (NGS)?
17. What is the benefit of performing clonality test by next- generation sequencing, and when should I consider it for clinical samples?
18. When is a NGS-based mutation profiling test indicated for hematopoietic and lymphoid disorders?
19. What are the limitations of current clinical NGS mutation profiling tests?
Case Presentations
Case 1
Learning Objective
Case History
Laboratory Findings
Genetic Study
Final Diagnosis
Follow-Up
Discussion
Case 2
Case History
Histologic Features
Genetic Study
Final Diagnosis
Discussion
Case 3
Learning Objective
Case History
Histologic Features and Other Laboratory Findings
Molecular Genetic Tests
Final Diagnosis
Follow-Up
Discussion
Case 4
Case History
Histologic Features
Laboratory Results
Molecular Study
Final Diagnosis
Discussion
Case 5
Case History
Laboratory Findings
Molecular Study
Final Diagnosis
Discussion
References
3: Evaluation of Excised Lymph Nodes
List of Frequently Asked Questions
1. What are the major clinical indications for excisional biopsy of lymph node?
2. What are the important instructions to the surgeons prior to excision of lymph node?
3. What intraoperative assessments (e.g., frozen section, touch prep/imprints) may be indicated when a fresh lymph node is obtained?
4. What are the important instructions for transportation of lymph node sample?
5. How should the lymph node excisional sample be grossed properly?
6. When should fresh lymphoid tissue be apportioned for additional studies (e.g., flow cytometry, cytogenetics, gene expression analysis) prior to fixation?
Flow Cytometry
Cytogenetics and Gene Expression Analysis
7. What are the likely differences in clinical presentations between reactive lymphadenopathy and nodal involvement by lymphoma?
8. What are the likely differences in clinical presentations between Hodgkin lymphoma and non-Hodgkin lymphoma?
9. Which types of lymphoid neoplasms often present with splenomegaly?
10. Which types of lymphoid neoplasms often present with neutropenia, anemia, thrombocytopenia, or pancytopenia?
11. Which lymphomas and non-leukemic hematolymphoid neoplasms can sometimes present as leukemia or have a leukemic phase?
12. What are the differential diagnoses in a patient who presents with an anterior/superior mediastinal mass?
13. Which types of hematolymphoid neoplasms tends to present with skin lesions, besides extracutaneous or nodal involvement?
14. Which anatomical sites (head/neck, axillary, thoracic, abdominal, retroperitoneal, inguinal, etc.) are more likely to be involved by particular lymphoid neoplasms or other hematolymphoid neoplasms?
15. How should the lymph node sections be examined microscopically?
16. What are the major morphological patterns of reactive lymphadenopathy?
17. Which clinical diagnoses are likely associated with a reactive follicular pattern in the lymph node?
18. What is the initial workup for the reactive appearing lymph node with dominant follicular pattern?
19. Which diagnoses are commonly associated with a paracortical pattern in reactive lymphadenopathy?
20. Which diagnoses are commonly associated with a sinus pattern in reactive lymphadenopathy?
21. Which diagnoses are commonly associated with a granulomatous pattern in reactive lymphadenopathy?
22. What are the major morphological patterns of lymphoma involvement in lymph node?
23. What are the major differential diagnoses and initial workup for lymphomas with follicular or nodular pattern?
24. What are the major differential diagnoses and initial workup for the lymph node with a diffuse infiltration by small cell lymphoma?
25. What are the major differential diagnoses and initial workup for the lymph node with an interfollicular growth pattern?
26. What are the major differential diagnoses and initial workup for the lymph node with a diffuse infiltration by blastoid cells?
27. What are the major differential diagnoses and initial workup for the lymph node with a diffuse infiltration by large tumor cells?
28. What are the major differential diagnoses and initial workup for the lymph node with a prominent sinus infiltration of tumor cells?
29. What is the initial workup for lymph node cases with morphologic features suggestive for classic Hodgkin lymphoma?
References
4: Lymphoid Pathology on Small Biopsies (FNA and Small Core) – Advantages and Limitations: Guidelines for Ancillary Studies According to Clinical Scenario and Morphology
List of Frequently Asked Questions
1. What are the “small biopsy” alternatives to an excisional lymph node biopsy and what is the optimal procedure for handling each?
FNA Cytology
CNB
2. What are the advantages and drawbacks of these techniques?
FNA
Advantages
Drawbacks
3. What is the difference in approach to small biopsies which are performed for initial diagnosis versus those performed in patients with previously treated disease? How are clinical findings used to guide interpretation of “small biopsy” of lymphoid
4. What are the diagnostic challenges using FNA for lymphoma diagnosis? What is the clinical relevance of misinterpretation between the true diagnosis and mimics with reference to mistreatment and/or wrong prognosis?
FNA
5. What are the advantages and limitations of Core Needle Biopsy for lymphoma diagnosis?
6. For small biopsies performed for initial diagnosis, which ancillary test results are diagnostic, suggestive of diagnosis, unreliable for diagnosis, or rule out the diagnosis?
Flow Cytometry
Immunohistochemistry (IHC)
Molecular Genetic Methods
Small Biopsies in Patients with Previously Diagnosed and Treated Disease
7. What is the work-up appropriate in patients with prior diagnosis of B-cell lymphomas? What are the special considerations to evaluate disease progression, secondary effects of prior treatment, and presence of therapeutic targets for additional trea
CD5+/CD10- B-NHLs
CD10+/CD5- B-NHLs (See also Chap. 5 for a detailed description of these entities)
CD5-/CD10- B-NHLs (See also Chap. 5, for a detailed descriptions of these entities)
8. What are the major pitfalls when diagnosing recurrent B-cell lymphomas on small biopsy?
9. What is the work-up of a small biopsy in patients with prior diagnosis of T/NK-cell lymphomas? What are the special considerations to evaluate disease progression, secondary effects of prior treatment, and presence of therapeutic targets for additi
10. What are the pitfalls in the diagnosis of HL with a small biopsy? What steps should be taken to avoid these pitfalls? (See also Chap. 9 for the basic classification and a detailed description of the subtypes of HL)
Case Presentations
Case 1 (Figs. 4.1, 4.2, and 4.3)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Diagnosis
Further Workup and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 2 (Figs. 4.4, 4.5, and 4.6)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Further Workup and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 3 (Figs. 4.7 and 4.8)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Further Workup and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 4 (Figs. 4.9, 4.10, 4.11, and 4.12)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Further Workup and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 5 (Figs. 4.13 and 4.14)
Learning Objectives
Clinical History
Histologic Findings
Differential Diagnosis
Further Workup and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 6 (Fig. 4.15)
Learning Objectives
Case History
Histologic Findings
Final Diagnosis
Take-Home Messages
References
5: Small B-Cell Lymphomas With and Without Plasmacytic Differentiation
List of Frequently Asked Questions
1. What are the major subtypes of small B-cell lymphomas? How to evaluate them?
2. What are the characteristic clinical, morphological, and immunophenotypic findings in CD5+ small B-cell lymphomas?
Monoclonal B-Cell Lymphocytosis (MBL)
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Mantle Cell Lymphoma (MCL)
3. What are the characteristic clinical, morphological, and immunophenotypic findings in CD10+ small B-cell lymphomas?
4. What are the characteristic clinical, morphological, and immunophenotypic findings in CD5-/CD10- small B-cell lymphomas?
Marginal Zone Lymphoma (MZL)
Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia (LPL/WM)
5. What are unusual morphological variants of follicular lymphoma which can mimic other lymphomas and reactive lymphoid proliferation?
6. What is the differential diagnosis of small B-cell lymphomas with plasmacytic or plasmacytoid differentiation?
7. How to distinguish small B-cell lymphomas with extensive plasmacytic differentiation from nodal involvement by a plasma cell neoplasm?
8. Which immunophenotypic markers are diagnostic or exclude a specific subtype of small B-cell lymphoma?
9. Which ancillary molecular/genetic tests are useful in the diagnosis or classification of small B-cell lymphomas?
10. Which are the most common genetic abnormalities seen in small B-cell lymphomas and how these results can be used for differential diagnosis along with immunophenotypic data? (Table 5.8)
11. Which ancillary tests provide prognostic and/or therapeutic information for small B-cell lymphomas?
12. How to distinguish small B-cell lymphomas from reactive follicular hyperplasia or paracortical hyperplasias and other reactive lymphadenopathies?
13. How frequently does each subtype of small B-cell lymphoma involve the bone marrow and what are their typical patterns of involvement? (Table 5.10)
14. How to distinguish bone marrow involvement by a small B-cell lymphoma from benign lymphoid aggregates?
15. What is considered an adequate specimen for diagnosis and classification of small B-cell lymphomas?
16. What information can be conveyed to the clinician during each workup stage of small B-cell lymphomas?
17. What should be the approach to provide maximum, but defensible, information from limited specimen or workup? What is a descriptive diagnosis appropriate in such situations?
18. When is a diagnostic comment necessary and what should be discussed in the diagnostic comment of small B-cell lymphomas?
19. When is it appropriate to seek external consultation for diagnosis or classification of small B-cell lymphomas?
Case Presentations
Case 1
Learning Objectives
Case History
Histologic Findings (Fig. 5.1a–c)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 5.1d–f)
Flow Cytometric Analysis (Fig. 5.2a–f)
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Case History
Histologic Findings (Fig. 5.3a, b)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 5.3c–h)
Final Diagnosis
Take-Home Messages
Case 3
Learning Objectives
Case History
Histologic Findings (Fig. 5.4a, b)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 5.4c–h)
Final Diagnosis
Take-Home Messages
Case 4
Learning Objectives
Case History
Histologic Findings (Fig. 5.5a, b)
Differential Diagnosis
IHC and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 5
Learning Objectives
Case History
Histologic Findings (Fig. 5.6a, b)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 5.6c–f)
Final Diagnosis
Take-Home Messages
Case 6
Learning Objectives
Case History
Histologic Findings (Fig. 5.7a–d)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 5.7e–f)
Final Diagnosis
Take-Home Messages
References
6: Large B-Cell Lymphoma
List of Frequently Asked Questions
1. How is diffuse large B-cell lymphoma (DLBCL) classified?
2. What are the major subtypes of DLBCL?
Classification of DLBCLs
3. What are the typical clinical features of DLBCL?
4. What are the common morphologic features of DLBCL?
5. What are the unusual morphologic variants of DLBCL?
6. What are the major genetic changes in DLBCL?
7. What are the important poor prognostic factors in DLBCL?
8. What are the major differential diagnoses of DLBCL?
9. What is the initial workup for the cases with morphologic features of DLBCL?
10. What is the further workup after initial studies of possible DLBCL cases?
11. What are the major pitfalls and recommendations in the workup of DLBCL with immunohistochemical stains?
12. What are the major clinicopathologic features of T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL)?
13. How is T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) distinguished from conventional DLBCL?
14. How is THRLBCL distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)?
15. What are the major clinicopathologic features of primary central nervous system DLBCL (PCNS DLBCL)?
16. What are the major clinicopathologic features of primary mediastinal (thymic) large B-cell lymphoma (PMLBCL)?
17. What is the initial workup for the cases with morphologic features of PMLBCL?
18. How is PMLBCL distinguished from mediastinal classic Hodgkin lymphoma (CHL)?
19. How is PMLBCL distinguished from conventional DLBCL?
20. What are the other differential diagnoses of PMLBCL?
21. What are the major clinicopathologic features of intravascular large B-cell lymphoma (IVLBCL)?
22. What are the major clinicopathologic features of primary cutaneous DLBCL, leg type (PCDLBCL-LT)?
23. What are the major clinicopathologic features of lymphomatoid granulomatosis (LyG)?
24. How is LyG distinguished from extranodal NK-/T-cell lymphoma, nasal type?
25. How is LyG distinguished from granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis?
26. What are the major clinical features of ALK+ large B-cell lymphoma (ALK+ LBCL)?
27. What are the typical morphologic and immunophenotypic features of ALK+ LBCL?
28. What are the common and uncommon chromosomal rearrangements in ALK+ LBCL?
29. How is ALK+ LBCL distinguished from ALK+ anaplastic large cell lymphoma?
30. What are the major differential diagnoses of a high-grade neoplasm in the lymph node with predominant sinus infiltrative pattern?
31. What are the major clinicopathologic features of plasmablastic lymphoma (PBL)?
32. How is PBL distinguished from solid variant of primary effusion lymphoma (solid PEL)?
33. How is PBL distinguished from plasmablastic plasmacytoma?
34. What are the major clinicopathologic features of extra-cavitary primary effusion lymphoma (PEL)?
35. What are the major clinicopathologic features of conventional PEL?
36. What is the initial workup for the cases with plasmablastic morphology?
37. What is the definition of EBV+ DLBCL, NOS?
38. What are the major clinicopathologic features of EBV+ DLBCL, NOS?
39. How is EBV+ DLBCL, NOS, distinguished from mucocutaneous ulcer (MCU)?
40. What is the definition of “high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangement?” (See also Chap. 7)
41. What are the major clinicopathologic features of “HGBL with MYC and BCL2 and/or BCL6 rearrangement?” (See also Chap. 7)
42. How is “HGBL, with MYC and BCL2 and/or BCL6 rearrangement” distinguished from Burkitt lymphoma? (See also Chap. 7)
Case Presentations
Case 1
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Initial Workup
Further Workup and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 3
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Initial Workup
Further Studies
Final Diagnosis
Take-Home Messages
Case 4
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Initial Workup
Further Workup
Final Diagnosis
Take-Home Messages
Case 5
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Initial Workup
Further Workup
Final Diagnosis
Take-Home Messages
Case 6
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 7
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 8
Learning Objective
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Message
Case 9
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 10
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Initial Workup
Further Workup
Final Diagnosis
Take-Home Messages
Case 11
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Initial Workup
Further Workup
Final Diagnosis
Take-Home Messages
Case 12
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Initial Workup
Further Studies
Final Diagnosis
Take-Home Messages
Case 13
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Initial Workup
Further Workup and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 14
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Initial Workup
Further Workup and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
References
7: High-Grade B-Cell Lymphoma
List of Frequently Asked Questions
1. What are “aggressive” B-cell lymphomas and what are “high-grade B-cell lymphomas”?
2. How are the major types of aggressive (high-grade) B-cell lymphomas defined?
3. What are the clinical features of the major types of aggressive (high-grade) B-cell lymphomas?
4. What are the morphological features of the major types of aggressive (high-grade) B-cell lymphomas?
5. What is the immunophenotype in each of the major types of aggressive (high-grade) B-cell lymphomas?
7. Why is the status of MYC a central defining characteristic of most aggressive/high-grade lymphomas?
8. What are the morphological mimics of aggressive (high-grade) B-cell lymphomas and how are they differentiated?
9. Which findings are suggestive of the diagnosis, which are definitively diagnostic, and which rule out the diagnosis of specific types of aggressive/high-grade B-cell lymphomas?
10. What is the prognostic and therapeutic significance of identification of these subtypes of aggressive/high-grade B-cell lymphomas?
Case Presentations
Case 1
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis (Fig. 7.6)
IHC Findings
Flow Cytometric Findings
Cytogenetic Analysis
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis (Fig. 7.7)
IHC Findings
Flow Cytometric Findings
Cytogenetic Analysis
Final Diagnosis
Take-Home Messages
References
8: Major Subtypes of Mature T- and NK-Cell Neoplasms
List of Frequently Asked Questions
1. What are the major subtypes mature T- and NK-cell neoplasms?
2. What is the most important clinical information to collect for this category?
3. What are the typical morphological findings in lymph node and extranodal sites involved by various subtypes of T- and NK-cell neoplasms?
4. What are the mimics and what is the clinical relevance of misinterpretation between the true diagnosis and mimics with reference to mistreatment and/or wrong prognosis?
5. Which morphological findings in the peripheral blood/BM/lymph node biopsy are reliably diagnostic? Which ones suggest the diagnosis? Which is (are) unreliable for diagnosis? Which findings rule out the diagnosis?
6. What is the minimal and optimal ancillary workup for diagnosis and subclassification of mature T- and NK-cell neoplasms?
7. Which ancillary test results are diagnostic, suggestive of diagnosis, unreliable for diagnosis, or rule out the diagnosis?
8. What is the workup to provide prognostic and therapeutic target information? (Corollary – what treatments are available for this entity?)
9. Which subtypes of mature T- and NK-cell neoplasms are clinically relevant and which are morphologically defined but have unproven/ minimal clinical relevance?
10. What is an adequate specimen for this condition?
11. What information can be conveyed to the clinician during each stage of the workup?
12. What should be the approach to provide maximum, but defensible information, from limited specimen or workup? When is a descriptive diagnosis appropriate in such situations?
13. When is a diagnostic comment necessary and what should be discussed in the diagnostic comment for mature T- and NK-cell neoplasms?
14. When is it appropriate to seek external consultation for mature T- and NK-cell neoplasms?
Case Presentations
Case 1
Learning Objectives
Case History
Histologic Features (Fig. 8.1a)
Differential Diagnosis
Immunohistochemistry and Other Ancillary Studies
Final Diagnosis
Case 2
Learning Objectives
Case History
Histologic Features (Fig. 8.1b)
Differential Diagnosis
Immunohistochemistry and Other Ancillary Studies
Final Diagnosis
Case 3
Learning Objectives
Case History
Histologic Features (Fig. 8.2)
Differential Diagnosis
Immunohistochemistry and Other Ancillary Studies
Final Diagnosis
Case 4
Learning Objectives
Case History
Histologic Features (Fig. 8.3)
Differential Diagnosis
Immunohistochemistry and Other Ancillary Studies
Final Diagnosis
Case 5
Learning Objectives
Case History
Histologic Features (Fig. 8.4)
Differential Diagnosis
Immunohistochemistry and Other Ancillary Studies
Final Diagnosis
Case 6
Learning Objectives
Case History
Cytologic Features
Differential Diagnosis
Flow Immunophenotype and Other Ancillary Studies
Final Diagnosis
References
9: Hodgkin Lymphomas
List of Frequently Asked Questions
1. What are the major subtypes of Hodgkin lymphoma?
2. What are the major clinicopathological features of Hodgkin lymphoma?
3. What are the typical morphological findings in Hodgkin lymphoma?
4. What are the most typical immunophenotypes of classic Hodgkin lymphoma?
5. How to distinguish CD30 and CD15 staining in classic Hodgkin cells from those in non-Hodgkin cells?
6. How to further classify classic Hodgkin lymphoma into subtypes?
7. How to distinguish nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) from classic Hodgkin lymphoma (cHL)?
8. What are the mimics of Hodgkin lymphoma and what are the clinical consequences of misinterpretation between Hodgkin lymphomas and their mimics?
9. How to distinguish nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) from progressive transformation of germinal centers (PTGC)?
10. How to distinguish nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) from T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL)?
11. How to distinguish nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) from follicular lymphoma (FL)?
12. How to distinguish classic Hodgkin lymphoma (cHL) from T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL)?
13. How to distinguish nodular sclerosis classic Hodgkin lymphoma (NSCHL) from primary mediastinal (thymic) large B-cell lymphoma (PMLBCL)?
14. How to distinguish classic Hodgkin lymphoma (cHL) from B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma (gray zone lymphoma, GZL)?
15. How to distinguish cHL from EBV+ diffuse large B-cell lymphoma NOS (EBV+ DLBCL)?
16. How to distinguish classic Hodgkin lymphoma (cHL) from peripheral T-cell lymphoma (PTCL)?
17. How to distinguish classic Hodgkin lymphoma from anaplastic large cell lymphoma (ALCL)?
18. How to distinguish lymphocyte-rich classic Hodgkin lymphoma (LRCHL) from mantle cell lymphoma (MCL)?
19. How to distinguish lymphocyte-rich classic Hodgkin lymphoma (LRCHL) from follicular lymphoma?
20. How to distinguish lymphocyte-depleted classic Hodgkin lymphoma (LDCHL) from histiocytic sarcoma?
21. For peripheral blood and bone marrow biopsies, what morphological findings are diagnostic and what findings are suspicious for classic Hodgkin lymphoma?
22. What is the minimal and optimal ancillary workup for the diagnosis of Hodgkin lymphomas?
23. What information provides prognostic and therapeutic target information for Hodgkin lymphomas?
24. What are adequate specimens for the diagnosis of Hodgkin lymphomas?
25. What information can be conveyed to the clinician during each stage of the workup?
26. When are comments necessary and what should be discussed in the comments for Hodgkin lymphoma?
27. When is it appropriate to seek external consultation for Hodgkin lymphomas?
Case Presentations
Case 1 (Fig. 9.1)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC Studies
Additional IHC Studies
Final Diagnosis
Take-Home Messages
Case 2 (Fig. 9.2)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC Studies
Additional IHC Studies
Final Diagnosis
Take-Home Messages
Case 3 (Fig. 9.3)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC Studies
Additional IHC Studies
Final Diagnosis
Take-Home Messages
Case 4 (Fig. 9.4)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC Studies
Additional IHC Studies
Final Diagnosis
Take-Home Message
Case 5 (Fig. 9.5)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC Studies
Additional IHC Studies
Final Diagnosis
Take-Home Messages
Case 6 (Fig. 9.6)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC Studies
Additional IHC Studies
Final Diagnosis
Take-Home Messages
Case 7 (Fig. 9.7)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC Studies
Additional IHC Studies
Final Diagnosis
Take-Home Messages
Case 8 (Fig. 9.8)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC Studies
Additional IHC Studies
Final Diagnosis
Take-Home Messages
Case 9 (Fig. 9.9)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC Studies
Additional IHC Studies
Final Diagnosis
Take-Home Messages
References
10: Posttransplant Lymphoproliferative Disorders (PTLDs)
List of Frequently Asked Questions
1. What is PTLD?
2. What is the spectrum of PTLDs?
3. How many categories of PTLDs?
4. What is required in a diagnostic workup of PTLD?
5. What are the key histologic features of nondestructive PTLDs, and how are they distinguished from other types of PTLDs?
6. What are the expected results of common immunomarkers for nondestructive PTLDs?
7. What are the expected genetic profiles of nondestructive PTLDs?
8. What is required to diagnose nondestructive PTLDs?
9. What are the key histologic features distinguishing polymorphic PTLD (P-PTLD) from nondestructive PTLDs?
10. What is the differential diagnosis of P-PTLD?
11. What are the expected results of common immunomarkers for P-PTLDs?
12. What are the expected genetic profiles of P-PTLDs?
13. How are monomorphic PTLDs (M-PTLDs) defined?
14. What are the entities included in monomorphic B-cell PTLDs?
15. What are the expected results of common immunomarkers for monomorphic B-cell PTLDs?
16. What are the expected genetic profiles of monomorphic B-cell PTLDs?
17. What are the entities included in monomorphic T/NK-cell PTLDs?
18. What are the expected results of common immunomarkers for monomorphic T/NK-cell PTLDs?
19. What are the expected genetic profiles of monomorphic T-cell PTLDs?
20. What is classic Hodgkin lymphoma PTLD (HL-PTLD)?
21. How is the previously so-called Hodgkin lymphoma-like PTLD (HL-like PTLD) differentiated from classic HL-PTLD?
22. How is PTLD on small tissue biopsy worked up?
23. How is PTLD distinguished from rejection?
Case Presentations
Cases 1–3 Learning Objectives
Case 1 (Fig. 10.1)
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 10.1c, d)
Final Diagnosis
Case 2 (Fig. 10.2)
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 10.2d, f)
Final Diagnosis
Case 3 (Fig. 10.3)
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 10.3b)
Final Diagnosis
Take-Home Messages
Case 4 (Fig. 10.4)
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 10.4c–f)
Final Diagnosis
Take-Home Messages
Case 5 (Fig. 10.5)
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 10.5b–d)
Final Diagnosis
Take-Home Messages
Case 6 (Fig. 10.6)
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 10.6b–f)
Final Diagnosis
Take-Home Messages
Case 7 (Fig. 10.7)
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 10.7b–f)
Final Diagnosis
Take-Home Messages
References
11: Immunodeficiency-Associated Lymphoproliferative Disorders Other Than PTLD (in Primary Immune Deficiency, HIV, and Iatrogenic Conditions)
List of Frequently Asked Questions
1. What are the major subtypes of primary immune deficiency (PID)?
2. How is autoimmune lymphoproliferative syndrome (ALPS) different from other PIDs? What are other entities that may mimic ALPS?
3. What are the types of benign lymphoid proliferation associated with the PID? What are the morphologic and phenotypic features?
4. What are the types of malignant lymphoproliferative conditions associated with the PID? What are the morphologic and phenotypic features?
5. What are the diagnostic criteria for lymphoproliferative disorders associated with PIDs? What is the minimal and optimal ancillary work-up for diagnosis and subclassification of these conditions?
6. What is an adequate specimen for the diagnosis of lymphoproliferative disorders associated with PID? When is it appropriate to seek external consultation?
7. What are the benign lymphoproliferative disorders associated with human immunodeficiency virus (HIV) infection?
8. What are the morphologic stages of HIV-related benign lymphadenopathy?
9. What is the differential diagnosis of HIV-related benign lymphadenopathy?
10. What are the common types of lymphomas associated with HIV?
11. What are the common genetic abnormalities and what are the main viral and molecular driving factors in HIV-associated lymphomas?
12. What is the definition of iatrogenic immunodeficiency-associated lymphoproliferative disorder (IA-LPD)?
13. Which clinical conditions and therapies are associated with IA-LPD?
14. How common is the IA-LPD?
15. Which therapeutic agents are associated with IA-LPD?
16. What is the median interval from initiation of therapy to the diagnosis of IA-LPD?
17. What are the types of IA-LPD?
Case Presentations
Case 1
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 3
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 4
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 5
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
References
12: Primary Extranodal Lymphomas of the GI Tract, Lung, CNS, and Skin with Common Mimics
List of Frequently Asked Questions
1. What are the lymphomas seen in the gastrointestinal (GI) tract?
2. What are the typical morphological findings in the two most common lymphomas of the stomach – MALT lymphoma and DLBCL?
3. What is the workup required for accurate diagnosis of MALT- type extranodal marginal zone lymphoma (MALT lymphoma)?
4. What are the distinctive features of large cell/aggressive lymphomas (EITL, MEITL, EBV+ DLBCL, BL, blastoid MCL) occurring in the intestines?
5. What are the distinctive features of small cell/indolent lymphomas and lymphoproliferative disorders involving the intestines?
6. What are the mimics of common lymphomas in the stomach and intestine?
7. What is primary CNS lymphoma (PCNSL) and which are the common PCNSLs?
8. What are the morphological and immunophenotypic findings in primary DLBCL of the CNS?
9. Which are other aggressive CNS lymphomas with unusual clinicopathological findings?
10. What are the clinicopathological findings in dural and epidural lymphomas?
11. What are the mimics of CNS lymphomas?
12. What is primary pulmonary lymphoma (PPL) and what are the morphological findings in the two most common PPLs – MALT lymphoma and DLBCL?
13. What are the features of lymphomatoid granulomatosis (LYG) in the lung?
14. What types of lymphomas commonly occur in the skin?
15. What are the differences between cutaneous marginal zone lymphoma and extranodal marginal zone lymphoma in other sites?
16. What is the most common type of primary cutaneous B-cell lymphoma?
17. What is the most common cutaneous T-cell lymphoma, and what are its characteristic features?
18. Which disorders are included in primary cutaneous CD30-positive lymphoproliferative disorders, and what are the features of primary cutaneous anaplastic large cell lymphoma?
19. Is lymphomatoid papulosis a lymphoma?
20. What is subcutaneous panniculitis-like T-cell lymphoma (SPTCL) according to the WHO (2017) classification, and what are its clinicopathological features?
Case Presentations
Case 1
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 13.3c and d)
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 12.21c)
Final Diagnosis
Take-Home Messages
Case 3
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 4
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 12.7d, e)
Final Diagnosis
Take-Home Messages
Case 5
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 12.22c–e)
Final Diagnosis
Take-Home Messages
Case 6
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 12.23c–f)
Final Diagnosis
Take-Home Messages
Case 7
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 12.15c and d)
Final Diagnosis
Take-Home Messages
Case 8
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 12.20b–d)
Final Diagnosis
Take-Home Messages
References
13: Lymphoid Neoplasms with “Benign” Clinical Course or Unclear Malignant Potential
List of Frequently Asked Questions
1. What are the diagnostic criteria for monoclonal B-cell lymphocytosis (MBL)?
2. What are the immunophenotypes of MBL?
3. What is a nodal equivalent of MBL?
4. What is in situ follicular neoplasia and how is it diagnosed?
5. What ancillary studies may be considered in ISFN?
6. What are the risks of in situ follicular neoplasia to progress to subsequent follicular lymphoma?
7. What is the difference between in situ follicular neoplasia and partial involvement by follicular lymphoma?
8. What are the types of indolent mantle cell lymphoma?
9. What are the clinical and pathologic features of leukemic non-nodal mantle cell lymphoma?
10. What are the diagnostic pitfalls for leukemic non-nodal mantle cell lymphoma?
11. What is in situ mantle cell neoplasia and how is it diagnosed?
12. What is the differential diagnosis of in situ mantle cell neoplasia?
13. What is the prognosis of in situ mantle cell neoplasia?
Case Presentations
Case 1 (Fig. 13.1)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Test Results
Final Diagnosis
Follow-Up
Take-Home Messages
Case 2 (Fig. 13.2)
Learning Objective
Case History
Histologic Findings
Differential Diagnosis
Ancillary Test Results
Final Diagnosis
Follow-Up
Take-Home Messages
Case 3 (Fig. 13.3)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Test Results
Final Diagnosis
Follow-Up
Take-Home Messages
Case 4 (Fig. 13.4)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Final Diagnosis
Follow-Up
Take-Home Messages
References
14: B-Cell Lymphoma in Children or Pediatric Type
List of Frequently Asked Questions
1. What is pediatric-type follicular lymphoma (PTFL)?
2. How is PTFL diagnosed?
3. What are the diagnostic criteria for PTFL?
4. What is the differential diagnosis of PTFL?
5. How to distinguish PTFL in adults and usual follicular lymphoma?
6. How to distinguish PTFL and large B-cell lymphoma with IRF4 rearrangement?
7. What is pediatric nodal marginal zone lymphoma (PNMZL)?
8. How is pediatric nodal marginal zone lymphoma diagnosed?
9. What is the differential diagnosis of pediatric nodal marginal zone lymphoma?
10. What is leukemia variant of Burkitt lymphoma (Burkitt cell leukemia, BCL)?
11. How is Burkitt cell leukemia diagnosed?
12. What is the differential diagnosis of Burkitt cell leukemia?
13. What is Burkitt-like lymphoma with 11q aberration?
14. How is Burkitt-like lymphoma with 11q aberration diagnosed?
15. What is the differential diagnosis of Burkitt-like lymphoma with 11q aberration?
Case Presentations
Case 1 (Figs. 14.1 and 14.2)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Test Results
Final Diagnosis
Follow-Up
Take-Home Messages
Case 2 (Figs. 14.3 and 14.4)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Test Results
Final Diagnosis
Take-Home Messages
Case 3 (Figs. 14.5 and 14.6)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Test Results
Final Diagnosis
Take-Home Messages
Case 4 (Figs. 14.7 and 14.8)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Test Results
Final Diagnosis
Take-Home Messages
References
15: Indolent T-/NK-Cell Lymphoproliferative Disorders
List of Frequently Asked Questions
1. What is the clinical manifestation of T-LGL leukemia?
2. What are the key histologic features for T-LGL leukemia?
3. What are the commonly used immunomarkers in T-LGL leukemia?
4. What is the differential diagnosis for T-LGL leukemia?
5. What is the clinical manifestation of chronic lymphoproliferative disorder of NK cells (CLPD-NK)?
6. What are the key histologic features for CLPD-NK?
7. What are the commonly used immunomarkers in CLPD-NK?
8. What is the differential diagnosis for CLPD-NK?
9. What is the clinical manifestation of indolent T-cell lymphoproliferative disorder of the GI tract (iT-LPD of the GI tract)?
10. What are the key histologic features for iT-LPD of the GI Tract?
11. What are the commonly used immunomarkers in iT-LPD of the GI tract?
12. What is the differential diagnosis for iT-LPD of the GI tract?
13. What is the clinical manifestation of NK-cell enteropathy?
14. What are the key histologic features of NK-cell enteropathy?
15. What are the commonly used immunomarkers in NK-cell enteropathy?
16. What is the differential diagnosis for NK-cell enteropathy?
17. What is the clinical manifestation of primary cutaneous CD4- positive small/medium T-cell LPD?
18. What are the key histologic features for primary cutaneous CD4- positive small/medium T-cell LPD?
19. What are the commonly used immunomarkers in primary cutaneous CD4- positive small/medium T-cell LPD?
20. What is the differential diagnosis for primary cutaneous CD4- positive small/medium T-cell LPD?
21. What is the clinical manifestation of primary cutaneous acral CD8- positive T-cell lymphoma?
22. What are the key histologic features for primary cutaneous acral CD8- positive T-cell lymphoma?
23. What are the commonly used immunomarkers in primary cutaneous acral CD8- positive T-cell lymphoma?
24. What is the differential diagnosis for primary cutaneous acral CD8- positive T-cell lymphoma?
Case Presentations
Case 1 (Fig. 15.1)
Learning Objectives
Case History
Histologic Findings (Fig. 15.1a–c)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 15.1d–f)
Final Diagnosis
Take-Home Messages
Case 2 (Fig. 15.2)
Learning Objectives
Case History
Histologic Findings (Fig. 15.2a–c)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 15.2d, e)
Final Diagnosis
Take-Home Messages
Case 3 (Fig. 15.3)
Learning Objectives
Case History
Histologic Findings (Fig. 15.3a, b)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 15.3c–g)
Final Diagnosis
Take-Home Messages
Case 4 (Fig. 15.4)
Learning Objectives
Case History
Histologic Findings (Fig. 15.4a, b)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 15.4c–f)
Final Diagnosis
Take-Home Messages
Case 5 (Fig. 15.5)
Learning Objectives
Case History
Histologic Findings (Fig. 15.5a, b)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 15.5c–e)
Final Diagnosis
Take-Home Messages
References
16: Composite Lymphoma
List of Frequently Asked Questions
1. What is composite lymphoma and what is the incidence of composite lymphoma?
2. Are the components of composite lymphoma clonally related?
3. What is the utility of assessment of clonality in composite lymphoma?
4. What are the hypotheses explaining the pathogenesis of composite lymphoma?
5. What are the major subtypes of composite lymphoma?
6. What are the typical morphological findings in composite lymphoma?
7. What are the main ancillary studies and their role in diagnosis of composite lymphoma?
8. What findings are suggestive for composite lymphoma diagnosis?
9. What are the main mimics of composite lymphoma?
10. What is an appropriate sample to diagnose composite lymphoma?
11. What is an appropriate reporting format of composite lymphoma?
12. What are the treatment considerations for composite lymphoma?
Case Presentations
Case 1
Learning Objectives
Case History
Histologic Findings (Fig. 16.1)
Morphologic Diagnosis
Flow Cytometry Analysis (Fig. 16.2)
Immunohistochemical Stains (Fig. 16.3)
FISH Study (Fig. 16.4)
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Case History
Laboratory Finding (Fig. 16.5)
Histologic Findings
Morphologic Diagnosis
Flow Cytometry Analysis (Fig. 16.6)
Immunohistochemical Stains (Fig. 16.7)
FISH Study
Mutational Study
Final Diagnosis
Take-Home Messages
Case 3
Learning Objectives
Case History
Histologic Findings (Fig. 16.8)
Morphologic Diagnosis (Figs. 16.9 and 16.10)
Flow Cytometry Analysis
Immunohistochemical Stains (Fig. 16.11)
Final Diagnosis
Take-Home Messages
Case 4
Learning Objectives
Case History
Histologic Findings (Fig. 16.12)
Flow Cytometry Analysis (Fig. 16.13)
Morphologic Diagnosis
Immunohistochemical Stains (Figs. 16.14 and 16.15)
Final Diagnosis
Take-Home Messages
Case 5
Learning Objectives
Case History
Histologic Findings
Morphologic Diagnosis (Fig. 16.16)
Flow Cytometry Analysis (Fig. 16.17)
Immunohistochemical Stains
IgH and TCR Gene Rearrangement (Fig. 16.18)
Final Diagnosis
Take-Home Messages
References
17: Histiocytic/Dendritic Cell Neoplasms: Primary and Transdifferentiated
List of Frequently Asked Questions
1. What are the major subtypes of histiocytic/dendritic cell neoplasms?
2. What are the typical morphological findings in histiocytic/dendritic cell neoplasms?
3. What are the mimics and what is the clinical relevance of misinterpretation between the true diagnosis and mimics with reference to mistreatment and/or wrong prognosis?
4. What is the minimal and optimal ancillary work-up for diagnosis and subclassification of histiocytic/dendritic cell neoplasms?
5. Which ancillary test results are diagnostic, suggestive of diagnosis, unreliable for diagnosis, or rule out the diagnosis?
6. What is the work-up to provide prognostic and therapeutic target information?
7. What should be the approach to provide maximum, but defensible information, from limited specimen or work-up? What is a descriptive diagnosis appropriate in such situations?
8. When is a diagnostic comment necessary and what should be discussed in the diagnostic comment for this entity?
9. Transdifferentiation or dedifferentiation?
10. When it is appropriate to seek external consultation for this entity?
Case Presentations
Case 1
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 3
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 4
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies
Final Diagnosis
Take-Home Messages
References
18: Typical Morphologic Patterns of Infectious and Other Reactive Lymphadenopathies
List of Frequently Asked Questions
Introduction
Special Notes on Specimen Adequacy
1. What are the major histologic patterns of infectious and other reactive lymphadenopathies?
Reactive Follicular Hyperplasia (RFH), DDx Including LAD Secondary to HIV/AIDS, Toxoplasma, Rheumatoid Arthritis, HV-CD, PTGC
2. What are typical findings in reactive follicular hyperplasia (RFH)?
3. What is the differential diagnosis (DDx) for RFH?
4. As a very typical entity that can display RFH, what other morphologic features can HIV/AIDS-related LAD exhibit?
5. Are histologic features alone sufficiently diagnostic for HIV/AIDS-related LAD?
6. What ancillary testing can help establish the diagnosis of HIV/AIDS-related LAD?
7. If RFH is not due to HIV/AIDS-related LAD, then what other histologic features could suggest another reactive entity (i.e., what else is in the DDx)?
8. What is the minimal histopathologic work-up in RFH?
9. What clinical and epidemiologic features are present in Toxoplasma LAD?
10. What are typical histologic and immunophenotypic findings for Toxoplasma LAD?
11. What ancillary testing can help establish the diagnosis of Toxoplasma LAD?
12. What clinical and epidemiologic features are present in lymphadenopathy associated with rheumatoid arthritis (RA-related LAD) and other autoimmune disorders?
13. What are typical histologic and immunophenotypic findings in RA-LAD and other autoimmune disorders?
14. What ancillary testing can help establish the diagnosis for RA-LAD?
15. What are clinical and epidemiologic features of unicentric Castleman disease (UCD)?
16. What are typical histologic findings in UCD?
17. What minimal histopathologic work-up and relevant clinical information can be used to avoid diagnostic pitfalls in UCD (like misdiagnosing HHV8-related multicentric Castleman disease [HHV8+ MCD] and early stage AITL)?
18. What clinical and epidemiologic features are present in progressive transformation of germinal centers (PTGC), another example of RFH?
19. What typical histologic findings are seen in PTGC?
20. What is the major DDx to consider and the minimal histopathologic work-up when PTGC is observed?
21. Considering all the entities in the DDx, what is the clinical relevance of misinterpretation in RFH?
22. In RFH, what information can be conveyed to the clinician? When is a diagnostic comment necessary? What is an adequate specimen?
23. When is consultation necessary in RFH?
Interfollicular to Diffuse Hyperplasia (IFH/DH), DDx Including LAD Secondary to EBV-Infectious Mononucleosis, Adult Onset Still’s Disease
24. What are typical findings in paracortical/interfollicular hyperplasia and diffuse hyperplasia (IFH/DH)?
25. What is the DDx in IFH/DH?
26. As a very typical entity that can display IFH/DH, what additional morphologic features does EBV-IM LAD exhibit?
27. Are immunohistologic features alone sufficiently diagnostic for EBV/IM-LAD?
28. What ancillary testing can help establish the diagnosis of EBV/IM-LAD?
29. If IFH/DH is not due to EBV-IM LAD, then what other histologic features could suggest another reactive entity (i.e., what else is in the DDx)?
30. What is the minimal histopathologic work-up in IFH/DH?
31. What clinical and epidemiologic features are present in adult-onset Still’s disease (AOSD), another entity which can present with IFH/DH?
32. As a very typical entity that can display IFH/DH, what other morphologic features does AOSD exhibit?
33. What ancillary testing can help establish diagnosis of AOSD?
34. Considering entities in the DDx, what is the clinical relevance of misinterpretation in IFH/DH?
35. In IFH/DH, what information can be conveyed to the clinician? When is a diagnostic comment necessary? What is an adequate specimen?
36. When is consultation necessary in IFH/DH?
Granulomatous, Suppurative, and Histiocyte-rich LAD (G/H-LAD), DDx Including LAD Secondary to Mycobacterial, Bacteria, and Fungal Infections; Sarcoidosis; Rosai-Dorfman-Destombes Disease, Kikuchi-Fujimoto Disease; Systemic Lupus Erythematosus
37. What are the typical morphologic findings in the major subtype of granulomatous and/or histiocyte-rich lymphadenopathy (G/H-LAD)?
38. What is the differential diagnosis for G/H-LAD patterns?
39. What is the minimal histopathologic and ancillary work-up for G/H-LAD?
40. As a very typical entity that displays necrotizing and/or non-necrotizing granulomatous LAD, what are salient clinical features in Mycobacterium tuberculosis complex lymphadenitis (MTBC LAD) and atypical mycobacterial/non-tuberculous mycobac
41. What histologic and special stain features suggest that a necrotizing and/or non-necrotizing granulomatous LAD is due to MTBC or NTM?
42. Are histologic and special stain findings alone sufficiently diagnostic for MTBC and NTM LAD?
43. What ancillary testing can help establish the diagnosis for MTBC and NTM LAD?
44. If necrotizing and/or non-necrotizing granulomas are not secondary to MTB or NTM, then what other histologic and special stain features could suggest another infectious entity (i.e., what else is in the DDx of infectious etiologies)?
45. What ancillary testing can help establish the specific infectious organism in fungal LAD?
46. What infectious organisms induce suppurative LAD?
47. What are typical histologic and immunophenotypic findings in suppurative LAD?
48. What ancillary testing can help establish the specific infectious organisms that induce suppurative LAD (includes Bartonella spp., Staphylococcus, Streptococcus, Lymphogranuloma venereum, Francisella, Brucella, Yersinia)?
49. After an exhaustive infectious disease work-up for etiologies of non-necrotizing (and even necrotizing and suppurative) granulomatous LAD, what else is in the DDx?
50. What clinical and epidemiologic features are present in sarcoid LAD?
51. What are typical histologic and special stain findings in sarcoid LAD?
52. What ancillary testing can help establish the diagnosis of sarcoid LAD?
53. Aside from sarcoidosis, what other non-infectious reactive agents can lead to non-necrotizing granulomatous LAD? What clinical and morphologic features allow for their recognition?
54. As a very typical entity that can display prominent foamy macrophage and/or epithelioid histiocyte-rich inflammatory LAD, what are the salient clinical and morphologic features in Mycobacterium avium-intracellulare complex (MAC) and M. lepr
55. What ancillary testing can help establish the diagnosis for MAC/NTM, or Hansen’s disease?
56. If prominent foamy macrophages and/or histiocyte-rich lymphadenitis is not due to mycobacterial infections (like MAC, NTM, or leprosy), then what else is in the DDx? Are there clues to distinguishing one from another?
57. What morphologic features and immunohistochemical findings would allow distinction of sinus histiocytosis from Rosai-Dorfman-Destombes disease and other neoplastic entities?
58. As an entity that can display massive necrosis and numerous histiocytes, what is Kikuchi-Fujimoto Disease disease (KFD)? How does it typically present clinically?
59. What are typical histologic and immunophenotypic findings in KFD?
60. What is the minimal histopathologic work-up for KFD?
61. What ancillary testing can help establish the diagnosis of KFD?
62. KFD and SLE (one of its histologic patterns) have nearly identical histologic and immunophenotypic findings. What features will allow distinction between KFD and SLE?
63. To summarize G/H-LAD: what would be the clinical relevance of misinterpretation?
64. What information can be conveyed to the clinician? When is a diagnostic comment necessary? What is an adequate specimen?
65. When is external consultation in G/H-LAD necessary?
Plasma Cell Rich Lymphadenopathy (PC-rich LAD), DDx Including LAD Secondary to Syphilis, IgG4-related Disease, Multicentric Castleman Disease
66. What are the typical morphologic findings in the major subtype of plasma cell-rich lymphadenopathy (PC-rich LAD)?
67. As a very typical entity that can display PC-rich LAD, what clinical and epidemiologic features do syphilitic (luetic) lymphadenitides exhibit?
68. What are typical histologic and immunophenotypic findings for syphilitic LAD?
69. What ancillary testing can support the diagnosis of syphilitic LAD?
70. What is the clinical relevance of not recognizing syphilitic LAD?
71. As a typical entity demonstrating PC-rich LAD, how does IgG4-related LAD (IgG4-R-LAD) present clinically?
72. What are typical histologic and immunophenotypic findings in IgG4-R-LAD and the minimal histopathologic work-up when suspected?
73. What clinical information and ancillary testing are highly suggestive of IgG4-RD and would support IgG4-R-LAD?
74. In LAD cases with increased IgG4+ plasma cells, what information can be conveyed to the clinician? When is a diagnostic comment necessary? What are the clinical implications of the diagnosis?
75. What is an adequate specimen in reactive LAD with increased IgG4+ plasma cells?
76. As another typical entity that displays PC-rich LAD, what salient clinical and epidemiologic features does multicentric Castleman Disease disease (MCD) exhibit?
77. What are typical histologic and immunophenotypic findings in MCD?
78. What is the clinical relevance of misinterpretation of PC-rich LAD?
79. What information can be conveyed to the clinician in LAD with features of plasma cell-rich Castleman disease? When is a diagnostic comment necessary?
80. What is an adequate specimen in LAD with MCD-like histopathology?
81. When is external consultation necessary in LAD with MCD-like histopathology?
LAD with Prominent Spindle Cell Proliferation
82. What are the typical entities in the major subtype of LAD with prominent spindled cell proliferations?
83. What are some selected entities displaying spindled morphology and how does one establish their diagnosis?
84. What is the clinical relevance of misinterpretation in this group of intranodal vascular/spindled cell proliferations?
85. When is consultation necessary in LAD with prominent spindled proliferation?
Case Presentations
Case 1
Learning Objectives
Case History
Histologic Findings (Fig. 18.31a–e)
Differential Diagnosis
IHC and Other Ancillary Studies
Final Histopathologic Diagnosis
Diagnostic Comment
Take-Home Messages
Case 2
Learning Objectives
Case History
Excisional Biopsy Histologic Findings (Figs. 18.32 and 18.33a)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 18.33b–f)
Final Clinicopathologic Integrated Diagnosis
Diagnostic Comment
Take-Home Messages
Case 3
Case History
Histologic Findings (Fig. 18.34a–d)
Differential Diagnosis Based on H&E Findings
IHC and Other Ancillary Studies (Figs. 18.34e, f and 18.35)
Final Histopathologic Diagnosis
Diagnostic Comment
Take-Home Messages
Case 4
Learning Objectives
Case History
Histologic Findings (Fig. 18.36a–c)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 18.36d, e)
Histologic Diagnosis and Comment on Needle Core Biopsy
Diagnostic Comment
Post-biopsy Clinical Follow-Up
Final Clinicopathologic Integrated Diagnosis
Take-Home Messages
Case 5
Learning Objectives
Case History
Histologic Findings (Fig. 18.37a–c)
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 18.37d–i)
Final Histologic Diagnosis
Additional Diagnostic Comments
Post-biopsy Clinical Hematology Work-Up
Clinician Integration of Post-biopsy Data
Final Integrated Diagnosis
Take-Home Messages
References
19: HHV8-Associated Lymphoproliferative Disorders
List of Frequently Asked Questions
1. What is HHV8?
2. What are the major types of HHV8-positive lymphoproliferative disorders (LPDs)?
3. What are other HHV8-positive LPDs besides these major types?
4. What are the typical morphological findings in this category?
5. What are the typical immunophenotypic findings in this category?
6. How does one distinguish between these major subtypes of HHV8-associated LPDs?
7. How do we distinguish HHV8-LPDs from other lymphomas with a similar morphology?
8. When to perform a HHV8 immunostain?
9. What are the treatment options for patients with HHV8-associated LPDs?
Case Presentations
Case 1 (Fig. 19.1)
Learning Objectives
Case History
Histologic Findings
Morphologic Diagnosis
Flow Cytometry Analysis
Immunohistochemical Stains
IgH and TCR Gene Rearrangement
Final Diagnosis
Take-Home Messages
Case 2 (Fig. 19.2)
Learning Objectives
Case History
Histologic Findings
Morphologic Diagnosis
Flow Cytometry Analysis
Immunohistochemical Stains
IgH and TCR Gene Rearrangement Analysis with Microdissection of Abnormal Germinal Centers
Final Diagnosis
Take-Home Messages
Case 3 (Fig. 19.3)
Learning Objectives
Case History
Histologic Findings
Morphologic Diagnosis
Flow Cytometry Analysis
Immunohistochemical Stains
IgH/K Gene Rearrangement Analysis
Final Diagnosis
Take-Home Messages
Case 4 (Fig. 19.4)
Learning Objectives
Case History
Histologic Findings
Morphologic Diagnosis
Flow Cytometry Analysis
Immunohistochemical Stains
IgH and TCR Gene Rearrangement Analysis
Final Diagnosis
Take-Home Messages
References
20: Bone Marrow at Initial Diagnosis: Clinical Associations and Approach to Diagnosis
List of Frequently Asked Questions
1. What is the relevance of morphological examination of bone marrow and the role of a surgical pathologist in the era of molecular diagnostics?
2. What are the indications of bone marrow examination?
3. Are there specific indications in certain patient groups?
4. What are the contraindications for a bone marrow biopsy?
5. What is the optimal procedure for obtaining and processing bone marrow samples?
6. What is the role of imaging studies in bone marrow examination?
7. What clinical information is needed to adequately evaluate a bone marrow specimen and what does the information imply for underlying disease?
8. Which laboratory test results are needed to adequately evaluate most bone marrow specimens?
9. Which additional laboratory tests are needed for specific indications listed above?
10. What is the optimal specimen for cytological examination of the marrow?
11. How to judge the quality of aspirate smear?
12. What information is obtained from cytological examination of the marrow?
13. What is the role of the core biopsy?
14. What additional studies should be considered in the evaluation of a bone marrow?
15. Which findings are of immediate importance and should be reported to a clinician?
16. What is the optimal organization of the bone marrow report?
17. What are the mimics and what is the clinical relevance of misinterpretation between the true diagnosis and mimics with reference to mistreatment and/or wrong prognosis?
18. Which morphological findings in the peripheral blood/BM aspirate/biopsy are reliably diagnostic? Which ones suggest the diagnosis? Which is (are) unreliable for diagnosis? Which findings rule out the diagnosis?
19. What should be the approach to provide maximum, but defensible information, from limited specimen or work-up?
20. When is a diagnostic comment necessary and what should be discussed in the diagnostic comment?
21. When is it appropriate to seek external consultation for a bone marrow biopsy?
References
21: Acute Leukemias
List of Frequently Asked Questions
1. What are the major types of acute leukemias?
2. What are the typical morphological findings in acute leukemias?
Acute Myeloid Leukemia vs Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Acute Promyelocytic Leukemia
Acute Myeloid Leukemia with Monocytic Differentiation
Acute Myelomonocytic Leukemia
Acute Monoblastic Leukemia and Acute Monocytic Leukemia.
Acute Myeloid Leukemia with t(8;21)(q22;q22.1); RUNX1-RUNX1T1
Acute Myeloid Leukemia with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
Pure Erythroid Leukemia
Acute Myeloid Leukemia with Myelodysplasia-Related Changes
Acute Lymphoblastic Leukemia
Acute Leukemia with Ambiguous Lineage
3. What are the mimics and what is the clinical relevance of misinterpretation between the true diagnosis and mimics with reference to mistreatment and/or wrong prognosis?
Acute Promyelocytic Leukemia vs Acute Myeloid Leukemia with Monocytic Differentiation or Acute Myeloid Leukemia, NOS
Acute Promyelocytic Leukemia vs Growth Factor Effect
Acute Myelomonocytic/Monocytic Leukemia vs Chronic Myelomonocytic Leukemia/Juvenile Myelomonocytic Leukemia
Pure Erythroid Leukemia vs Acute Myeloid Leukemia, Not Otherwise Specified, Erythroid Predominant Myelodysplastic Syndrome and Reactive Erythroid Hyperplasia
Transient Abnormal Myelopoiesis Associated with Down Syndrome vs Acute Megakaryoblastic Leukemia
Mimics of Acute Leukemia
B-cell Prolymphocytic Leukemia Mimicking Acute Leukemia
T-cell Prolymphocytic Leukemia and HTLV1+ Adult T-Cell Leukemia Lymphoma (ATLL) Mimicking Acute Leukemia
Aggressive B-Cell Lymphoma Involving Peripheral Blood and/or Bone Marrow Mimicking Acute Leukemia
Atypical Chronic Lymphocytic Leukemia Mimicking Acute Leukemia
4. Which morphological findings in the peripheral blood/BM aspirate/biopsy are reliably diagnostic of acute leukemia? Which ones suggest the diagnosis? Which is (are) unreliable for diagnosis? Which findings rule out the diagnosis?
Acute Myeloid Leukemia with the Presence of Auer Rods in Blasts
Acute Myeloid Leukemia with Monocytic Differentiation
Acute Leukemia with <20% Blasts
Aleukemic Acute Leukemia
Cases with Hypercellularity, Fibrosis, or Dysplasia
Hematogone Hyperplasia
5. What is the minimal and optimal ancillary workup for diagnosis and subclassification of acute leukemias?
6. Which ancillary test results are diagnostic, suggestive of diagnosis, unreliable for diagnosis, or rule out the diagnosis?
Immunophenotyping (Flow Cytometry and/or Immunohistochemistry)
Cytogenetic Studies (Karyotype and/or FISH)
Molecular Studies
7. What is the workup to provide prognostic and therapeutic target information? (Corollary – what treatments are available for this entity?)
Reticulin Stain on Core Biopsy
Immunophenotyping (Flow Cytometry)
Chromosome Analysis and FISH
Molecular Studies
8. Which subtypes of this entity are clinically relevant, and which are morphologically defined but have unproven/minimal clinical relevance?
AML with Minimal Differentiation, AML Without Maturation, and AML with Maturation are Morphologically Distinct but Similar in Prognosis
9. What is an adequate specimen for this condition?
Bone Marrow Aspirate
Bone Marrow Core Biopsy
Peripheral Blood
10. What information can be conveyed to the clinician during each stage of the workup?
11. What should be the approach to provide maximum, but defensible information, from limited specimen or workup? What is a descriptive diagnosis appropriate in such situations?
12. When is a diagnostic comment necessary, and what should be discussed in the diagnostic comment for this entity?
13. When it is appropriate to seek external consultation for this entity?
Case Presentations
Case 1 (Fig. 21.15)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 2 (Fig. 21.16)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 3 (Fig. 21.17)
Learning Objectives
Case History
Histologic Findings
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 4 (Fig. 21.18)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 5 (Fig. 21.19)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 6 (Fig. 21.20)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 7 (Fig. 21.21)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 8 (Fig. 21.22)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
References
22: Chronic Myeloid Leukemia
List of Frequently Asked Questions
1. How is chronic myeloid leukemia defined? What is its presentation and natural course?
2. What are the morphological features of CML in CP, AP, and BP?
3. What are the diagnostic criteria for CML-CP?
Peripheral Blood (Fig. 22.1a)
Bone Marrow (Figs. 22.1b and 22.2)
4. What are the diagnostic criteria for CML-AP?
Hematological Criteria
Cytogenetic Criteria
Provisional Response-to-TKI Criteria
Presumptive Evidence of AP
5. What are the diagnostic criteria for CML-BP?
Presumptive Evidence of BP
6. What are the diagnostic and prognostic work-ups for CML?
7. What is the differential diagnosis of CML?
8. How is CML treated?
9. How is CML treatment response monitored?
10. What are the mechanisms of TKI resistance?
11. What is the significance of BCR-ABL1 transcript subtypes?
12. What is the significance of variant Ph?
13. What is the significance of additional chromosomal abnormalities in Ph+ cells?
14. What is the significance of chromosomal abnormalities in Ph-negative cells?
15. What other types of de novo leukemia are Ph+?
16. What is the significance of Ph acquired during therapy of MDS and acute leukemia?
17. What is the significance of Ph acquired during therapy of Ph-negative MPN?
Case Presentations
Case 1
Learning Objectives
Case History
Morphologic Findings
Differential Diagnosis
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Case History
Morphologic Findings
Differential Diagnosis
Final Diagnosis
Take-Home Message
Case 3
Learning Objectives
Case History
Morphologic Findings
Differential Diagnosis
Final Diagnosis
Take-Home Messages
Case 4
Learning Objectives
Case History
Morphologic Findings
Differential Diagnosis
Final Diagnosis
Take-Home Message
Case 5
Learning Objectives
Case History
Morphologic Findings
Differential Diagnosis
Final Diagnosis
Treatment
Take-Home Messages
Case 6
Learning Objectives
Case History
Morphologic Findings
Differential Diagnosis
Final Diagnosis
Treatment
Take-Home Message
Case 7
Learning Objectives
Case History
Morphologic Findings
Differential Diagnosis
Diagnosis
Morphologic Findings
Differential Diagnosis
Diagnosis
Morphologic Findings
Differential Diagnosis
Final Diagnosis
Take-Home Messages
References
23: Chronic Myeloproliferative Neoplasms (Other Than Chronic Myeloid Leukemia)
List of Frequently Asked Questions
1. What are the major subtypes of myeloproliferative neoplasms (MPNs)?
2. What are the typical morphological findings in MPNs?
CNL
PV
PMF
ET
CEL, NOS
MPN-U
Mastocytosis
Myeloid/Lymphoid Neoplasms with Eosinophilia and Gene Rearrangement
3. What are mimics of MPNs, and what are the clinical implications of misinterpretation of the true diagnosis and mimics with regard to mistreatment and/or prognosis?
4. Which morphological findings in the peripheral blood/BM aspirate/ biopsy are reliably diagnostic? Which ones suggest the diagnosis? Which is (are) unreliable for diagnosis? Which findings rule out the diagnosis?
5. What is the minimal and optimal ancillary workup for diagnosis and subclassification of MPNs?
6. Which ancillary test results are diagnostic, suggestive of diagnosis, unreliable for diagnosis, or rule out the diagnosis?
7. What is the workup to provide prognostic and therapeutic target information? What treatments are available for MPNs?
8. Which subtypes of MPNs are clinically relevant and which are morphologically defined but have unproven or minimal clinical relevance?
9. What is an adequate specimen for MPNs?
10. What information can be conveyed to the clinician during each stage of the workup?
11. What should be the approach to provide maximum, but defensible, information from limited specimen or workup? What is an appropriate descriptive diagnosis in such situations?
12. When is a diagnostic comment necessary and what should be discussed in the diagnostic comment for MPNs?
13. When is it appropriate to seek external consultation for this entity?
Case Presentations
Case 1
Learning Objectives
Case History
Histologic Findings
Ancillary Studies
Final Diagnosis
Diagnostic Comment
Take-Home Messages
Case 2
Learning Objectives
Case History
Histologic Findings (Fig. 23.3)
Ancillary Studies
Final Diagnosis
Diagnostic Comment
Additional Workup
Take-Home Messages
Case 3
Learning Objectives
Case History
Histologic Findings (Fig. 23.4)
Ancillary Studies
Final Diagnosis
Take-Home Messages
References
24: Myelodysplastic Syndromes
Frequently Asked Questions
1. What are the major subtypes of myelodysplastic syndromes (MDS)?
2. What are the WHO criteria for myelodysplasia, cytopenia and ring sideroblasts?
3. What are the major changes in the 2017 WHO classification?
4. What are the typical clinical, laboratory, and morphological findings of MDS?
5. What are the MDS mimics and what is the clinical impact of misdiagnosis?
6. What germline predispositions and inherited syndromes are relevant to MDS and its differential diagnosis?
7. What other pre-MDS conditions are relevant to MDS differential diagnosis?
8. What are the practical guidelines for diagnosis of MDS? What are the findings suggestive of MDS and the findings that rule out MDS?
9. What is the minimal and optimal ancillary workup for MDS and subclassification of MDS?
10. What additional ancillary tests are helpful for the diagnosis of MDS?
11. What is the workup to provide prognostic information?
12. What workup provides therapeutic target information for MDS?
13. What is an appropriate practical approach for diagnosis of MDS? When is a diagnostic comment necessary and what should be discussed in the diagnostic comment for this entity? When is it appropriate to seek external consultation for this entity?
14. Which features set MDS apart from closely related hematologic neoplasms?
Case Presentations
References
25: Myelodysplastic/Myeloproliferative Neoplasms
Frequently Asked Questions
1. What are myelodysplastic and myeloproliferative neoplasms (MDS/MPN), and what are the major subtypes of MDS/MPN?
Chronic Myelomonocytic Leukemia (CMML)
2. What are the laboratory and morphologic findings of CMML?
3. What are the mimics and differential diagnostic considerations for CMML?
4. What work-up provides prognostic information for CMML?
5. What work-up provides information regarding therapeutic targets and clinical management information for CMML?
Atypical Chronic Myeloid Leukemia, BCR-ABL1-Negative (aCML, BCR-ABL1-)
6. What are the laboratory and morphologic findings of aCML?
7. What are the mimics and differential diagnostic considerations for aCML?
8. What work-up provides prognostic information for aCML?
9. What work-up provides therapeutic targets and clinical management information for aCML?
Juvenile Myelomonocytic Leukemia (JMML)
10. What are the laboratory and morphologic findings of JMML?
11. What are the mimics and differential diagnostic considerations for JMML?
12. What work-up provides prognostic information for JMML?
13. What work-up provides therapeutic targets and clinical management information for JMML?
MDS/MPN with Ring Sideroblasts and Thrombocytosis (MDS/MPN-RS-T)
14. What are the laboratory and morphologic findings of MDS/MPN-RS-T?
15. What are the mimics and differential considerations for MDS/MPN-RS-T?
16. What work-up provides prognostic information for MDS/MPN-RS-T?
17. What work-up provides therapeutic targets and clinical management information for MDS/MPN-RS-T?
Myelodysplastic/Myeloproliferative Neoplasms, Unclassifiable (MDS/MPN-U)
18. What are the laboratory and morphologic findings of MDS/MPN-U?
19. What work-up provides therapeutic targets and clinical management information for MDS/MPN-U?
20. Which morphological and laboratory findings in the PB/BM aspirate/biopsy are reliably diagnostic for MDS/MPN? Which ones suggest the diagnosis? Which is (are) unreliable for diagnosis? Which findings rule out the diagnosis?
21. What is the minimal and optimal ancillary work-up for diagnosis and subclassification of the different categories of MDS/MPN?
22. What is an appropriate practical approach for diagnosis of MDS/MPN? When is a diagnostic comment necessary, and what should be discussed in the diagnostic comment for this entity? When is it appropriate to seek external consultation for this e
Case Presentations
Case 1
Learning Objectives
Case History
Histologic Findings
Other Ancillary Studies
Differential Diagnosis
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Case History
Histologic Findings
Other Ancillary Studies
Differential Diagnosis
Final Diagnosis and Follow Up
Take-Home Messages
Case 3
Learning Objectives
Case History
Histologic Findings
Other Ancillary Studies
Differential Diagnosis
Final Diagnosis and Follow Up
Take-Home Messages
References
26: Plasma Cell Neoplasms (Including Plasma Cell Myeloma)
List of Frequently Asked Questions
1. What is the clinical and pathological spectrum of plasma cell neoplasms?
2. What are the typical morphological findings in plasma cell myeloma and other plasma cell neoplasms?
3. Which diagnostic tests are used to detect monoclonal gammopathy and to quantify monoclonal immunoglobulin produced by plasma cell neoplasms?
4. How to quantify myeloma plasma cells in bone marrow samples?
5. What is the immunophenotype of reactive and neoplastic plasma cells?
6. How to confirm the monoclonality of neoplastic plasma cells?
7. What additional clinical and radiographic evidence should be obtained in a suspected case of plasma cell myeloma?
8. How to differentiate non-IgM MGUS, asymptomatic (smoldering) myeloma, and symptomatic multiple myeloma?
9. What are the plasma cell myeloma variants and how to diagnose each variant type?
10. How to define and diagnose solitary plasmacytoma and primary amyloidosis?
11. What is the clinical utility of fluorescent in-situ hybridization (FISH) analysis in plasma cell myeloma?
12. What are the mimics of plasma cell neoplasm that could be misinterpreted and mistreated as plasma cell myeloma?
13. What are POEMS syndrome and TEMPI syndrome?
14. How to evaluate and report response to treatment of symptomatic multiple myeloma?
Case Presentations
Learning Objectives
Case 1
Case History
Initial Workup and Management
Histologic Findings and Additional Workup
Differential Diagnosis
Final Diagnosis
Take-Home Messages
Case 2
Case History
Initial Workup and Management
Histologic Findings and Additional Workup
Differential Diagnosis
Final Diagnosis
Take-Home Message
References
27: Bone Marrow Involvement by Lymphoid Neoplasms
List of Frequently Asked Questions
1. What is the significance of bone marrow examination in the diagnostic work-up of patients with lymphoma?
2. What is the frequency of bone marrow involvement in various lymphoid neoplasms?
3. What is an adequate specimen for staging of lymphoma in bone marrow?
4. What ancillary studies are useful for the diagnosis of lymphoid neoplasms in bone marrow?
5. What are the challenges in the diagnosis of lymphoid neoplasms in bone marrow?
6. What are the pitfalls in the evaluation for residual lymphoid neoplasms in bone marrow during or after treatment?
7. What essential information should be included in the pathology report on bone marrow specimens involved by lymphoma?
8. How does one distinguish reactive lymphoid aggregates from lymphoma?
9. What are the common infiltration patterns of lymphoma in the bone marrow, and what is their significance for classification?
10. What is the definition of discordant bone marrow involvement in non-Hodgkin lymphoma, and what is its significance?
11. What is the significance of detecting a small monoclonal B-cell population in bone marrow in a patient without previously diagnosed lymphoma?
Characteristic Features of Specific Lymphomas Involving the Bone Marrow
12. What are the distinctive pathologic features of splenic marginal zone lymphoma in bone marrow, and what are the important differential diagnostic considerations?
13. What are the typical pathologic features and caveats in the diagnosis of classic hairy cell leukemia in bone marrow?
14. What are the main morphologic and immunophenotypic characteristics and challenges in the diagnosis of mature T-/NK-cell neoplasms in the bone marrow?
15. What are the pathologic features of angioimmunoblastic T-cell lymphoma in bone marrow?
16. What are the typical pathologic features of T-cell large granular lymphocytic (T-LGL) leukemia in bone marrow, and what are the important differential diagnostic considerations?
17. What are the typical pathologic features of hepatosplenic T-cell lymphoma in the bone marrow, and what are the important differential diagnostic considerations?
18. What are the typical histologic features of Hodgkin lymphoma (HL) in bone marrow, and what are the important differential diagnostic considerations?
Case Presentations
Case 1
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 27.9d, e)
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 27.10c–e)
Final Diagnosis
Take-Home Messages
Case 3
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
IHC and Other Ancillary Studies (Fig. 27.11c–e)
Final Diagnosis
Take-Home Messages
Case 4
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Final Diagnosis
Take-Home Messages
Case 5
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Final Diagnosis
Take-Home Messages
References
28: Bone Marrow Involvement by Metastases and Granulomatous Conditions
List of Frequently Asked Questions
1. What are typical peripheral blood findings in patients with metastatic disease involving the bone marrow (BM)?
2. What are common clinical findings present when metastatic disease involves the BM?
3. What is the appropriate BM specimen to detect metastatic disease?
4. What are the major non-hematopoietic adult malignancies that metastasize to the BM?
5. What are the major non-hematopoietic pediatric malignancies that metastasize to the BM?
6. What is the differential diagnosis for metastatic disease to the BM?
7. What is the differential diagnosis for the etiology of BM granulomas?
8. What is the appropriate work-up for granulomas in the BM?
Case Presentations
Case 1
Learning Objectives
Case History
Morphologic Findings
Differential Diagnosis
Immunohistochemical Findings
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Case History
Morphologic Findings
Differential Diagnosis
Immunohistochemical Findings
Final Diagnosis
Take-Home Messages
References
29: Bone Marrow Findings in Congenital/Hereditary Conditions
List of Frequently Asked Questions
1. What is the role of a hematopathologist in diagnosing congenital/ hereditary conditions by evaluating peripheral blood and/or bone marrow findings?
2. What is “bone marrow failure syndrome,” and what are the common inherited bone marrow failure syndromes?
3. What is the general approach in diagnosing bone marrow failure syndromes?
4. What are the major findings in patients with Fanconi anemia?
5. What are the abnormalities of hematopoietic system seen in patients with Down syndrome?
6. What are the broad categories and the overall frequency of myeloid neoplasm with germline predisposition?
7. What are the distinguishing features of the major entities under “myeloid neoplasms with germline predisposition without a preexisting disorder or organ dysfunction”?
8. What are the major entities under “myeloid neoplasms with germline predisposition and preexisting platelet disorders”? What are the clinical and morphologic features of these entities?
9. What are the major entities under “myeloid neoplasms with germline predisposition and other organ dysfunction”? What are the clinical and morphologic features of these entities including germline GATA2 mutation?
10. What could be a potential pitfall for diagnosing myeloid neoplasms in the setting of underlying germline condition?
11. When and which tissue should be tested to confirm the presence of a germline condition in patients with myeloid neoplasms?
12. What are the bone marrow features of common variable immunodeficiency (CVID)?
13. What is familial hemophagocytic lymphohistiocytosis (FHL)? What are the peripheral blood and bone marrow findings in FHL?
14. How is FHL diagnosed and what are the diagnostic pitfalls?
15. What is autoimmune lymphoproliferative syndrome (ALPS), and what are the peripheral and bone marrow findings in ALPS?
16. What are the peripheral and bone marrow findings in the major entities of lysosomal storage diseases?
Case Presentations
Case 1 (Fig. 29.2)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 2 (Fig. 29.3)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 3 (Fig. 29.4)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 4 (Fig. 29.5)
Learning Objective
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Message
Case 5 (Fig. 29.6)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 6 (Fig. 29.7)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 7 (Fig. 29.8)
Learning Objective
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 8 (Fig. 29.9)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 9 (Fig. 29.10)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 10 (Fig. 29.11)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Final Diagnosis
Take-Home Messages
Case 11 (Fig. 29.12)
Learning Objective
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 12 (Fig. 29.13)
Learning Objective
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Message
Case 13 (Fig. 29.14)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Follow-Up
Take-Home Messages
Case 14 (Fig. 29.15)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 15 (Fig. 29.16)
Learning Objective
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 16 (Fig. 29.17)
Learning Objectives
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 17 (Fig. 29.18)
Learning Objective
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Message
Case 18 (Fig. 29.19)
Learning Objective
Case History
Histologic Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
References
30: Bone Marrow Involvement by More Than One Entity of Hematolymphoid Neoplasm
List of Frequently Asked Questions
1. What are the common combinations of concurrent hematolymphoid neoplasms in bone marrow?
2. What are the common clinical and diagnostic settings in which dual hematolymphoid neoplasms may be identified? Can such dual populations be appreciated on aspirate smear or H&E stained core biopsy?
3. What are the potential diagnostic errors in the presence of coexisting neoplasms, and what is the clinical relevance of misinterpretation with reference to mistreatment and/or wrong prognosis?
4. Which morphological findings in the bone marrow biopsy are reliably diagnostic of dual involvement? Which ones suggest the diagnosis? Which is (are) unreliable for diagnosis? Which findings rule out the diagnosis?
5. What is the minimal and optimal ancillary work up required to ensure correct diagnosis and accurate classification of both malignancies involving the marrow?
6. Which ancillary test results are diagnostic, suggestive of diagnosis, unreliable for diagnosis, or rule out the diagnosis?
7. How to distinguish small mature B-cell leukemia/lymphoma with plasmacytoid differentiation from concurrent small B-cell leukemia/lymphoma and plasma cell neoplasm? How to dissect the two B-cell neoplasms in order to determine biclonality or monoclo
8. Which subtypes of marrow involvement by more than one entity are clinically relevant and which are morphologically defined but have unproven/minimal clinical relevance?
9. What is an adequate specimen for this condition?
10. What information can be conveyed to the clinician during each stage of the work up?
11. What should be the approach to provide maximum, but defensible information, from limited specimen or work-up? What is a descriptive diagnosis appropriate in such situations?
12. When is it appropriate to seek external consultation for this condition?
Case Presentations
Case 1
Learning Objectives
Case History
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 3
Learning Objectives
Case History
Bone Marrow Morphology
Immunohistochemical Findings
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
Case 4
Learning Objectives
Case History
Bone Marrow Morphology
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
References
31: Detection of Minimal Residual Disease
List of Frequently Asked Questions
1. What is minimal residual disease?
2. Why is minimal residual disease testing clinically important?
3. Which methods are commonly used in minimal residual disease detection and how do they work?
4. What are the strengths and limitations of next-generation-sequencing applied in MRD testing?
5. Are there standard antibody panels used in MFC- based MRD testing?
6. How is MRD identified in the MFC data analysis?
7. Which pre-analytic factors should be considered in MRD testing?
Case Presentations
Case 1
Learning Objective
Case History
Findings (Fig. 31.2)
Differential Diagnosis
Final Diagnosis
Take-Home Messages
Case 2
Learning Objective
Case History
Findings
Differential Diagnosis
Final Diagnosis
Take-Home Message
Case 3
Learning Objective
Case History
Findings (Fig. 31.5)
Differential Diagnosis
Final Diagnosis
Take-Home Messages
Case 4
Learning Objective
Case History
Findings (Fig. 31.6)
Differential Diagnosis
Final Diagnosis
Take-Home Messages
References
32: Therapy-Induced Marrow Changes
List of Frequently Asked Questions
Introduction
1. What are the major patterns of drug induced bone marrow changes?
2. What are the typical morphological findings in various patterns of therapy induced marrow changes?
3. What are the mimics of therapy induced marrow changes? What is the clinical relevance of misinterpretation between the true diagnosis and mimics?
4. Which morphological findings in the peripheral blood and bone marrow are reliably diagnostic? Which ones suggest the diagnosis? Which findings rule out the diagnosis?
5. What is the minimal and optimal ancillary work up for diagnosis and sub-classification in these cases? Which test results are specific and which should be interpreted with caution?
6. Which findings in these cases identify clinically relevant entities and which ancillary tests can provide prognostic and therapeutic target information for subsequent management?
7. What is an adequate marrow specimen in previously treated patients?
8. What information should be conveyed to the clinician during each stage of the work up and/ or when the specimen is limited?
9. When is a diagnostic comment necessary and what should be discussed in the comment in these cases?
10. When is it appropriate to seek external consultation in these cases?
Case Presentations
Case 1
Learning Objectives
Case History
Differential Diagnosis
Histologic Findings
Ancillary Studies Performed on the Bone Marrow
Final Diagnosis
Take-Home Messages
Case 2
Learning Objectives
Case History
Laboratory Findings (Fig. 32.11)
Histologic Findings (Fig. 32.12)
Differential Diagnosis
Ancillary Studies
Final Diagnosis
Take-Home Messages
References
Index