Arber DA, Orazi A, Hasserjian, R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127(20): 2391-2405
Swerdlow S. Elias Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016; 127(20):2375-2390
2. Which gene mutation is strongly associated with chronic neutrophilic leukemia (CNL)?
CSF3R.
3. What is the new subtype (cytogenetic abnormality) in myeloid/lymphoid neoplasms associated with eosinophilia?
PCM1-JAK2: t(8;9)(p22;p24.1) (provisional).
May respond to JAK2 inhibitors.
Bone marrow shows left-shifted erythroid predominance, lymphoid aggregates and myelofibrosis.
4. Is refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T, a provisional entity within the MDS/MPN unclassifiable group) now termed MDS/MPN with ring sideroblasts and thrombocytosis, a real entity?
Yes. Presence of a SF3B1 mutation or, in the absence of SF3B1 mutation, no history of recent cytotoxic or growth factor therapy that could explain the myelodysplastic /myeloproliferative features
5. Which gene mutations are commonly associated with aCML?
SETBP1 and/or ETNK1 mutations in up to a third of cases
6. Is the name of chronic myelogenous leukemia changed to chronic myeloid leukemia?
Yes.
7. Which new gene mutation is added to the diagnostic criteria for juvenile myelomonocytic leukemia (JMML)?
CBL, germline mutation and LOH
8. Is splenomegaly required for the diagnosis of JMML?
Yes.
9. Terminology change in MDS: “refractory anemia” or “refractory cytopenia” has been replaced by “myelodysplastic syndrome” followed by the appropriate modifiers: single vs multilineage dysplasia, ring sideroblasts, excess blasts, or the del(5q) cytogenetic abnormality. True or false?
True.
10. Childhood MDS has been changes. True or false?
False. There are no changes to childhood MDS; refractory cytopenia of childhood remains as a provisional entity within this category.
11. Erythroid/myeloid leukemia does not exist anymore. True or false?
True. There is a major change in the diagnostic criteria for acute erythroid leukemia (erythroid precursors >50% of all BM cells). In the updated classification, the denominator used for calculating blast percentage is all nucleated BM cells, not just the “non-erythroid cells.” The subcategory of acute erythroid leukemia, erythroid/myeloid type (previously defined as a case with >50% BM erythroid precursors and >20% myeloblasts among non-erythroid cells) has been removed from the AML category, and classified to MDS (mostly with excess blasts). Pure erythroid leukemia remains as an AML, NOS subtype and is now the only type of acute erythroid leukemia (>80% immature erythroid precursors with >30% proerythroblasts)
12. May the entity MDS with isolated del(5q) be diagnosed with one additional cytogenetic abnormality except monosomy 7 or del(7q)?
Yes.
13. CHIP can be seen in a healthy person. What does CHIP mean?
Clonal hematopoiesis of indeterminate potential.
Although some patients with CHIP subsequently develop MDS, the natural history of this condition is not yet fully understood; thus, the presence of MDS-associated somatic mutations alone is not considered diagnostic of MDS in this classification, even in a patient with unexplained cytopenia.
14. If an SF3B1 mutation is identified, a diagnosis of MDS-RS may be made even if ring sideroblasts comprise less than 15% of erythroblasts, True or false?
True.
15. Is AML with BCR-ABL1 a new provisional entity?
Yes.
16. Is AML with mutated RUNX1 a new provisional entity?
Yes.
17. B-ALL in germline TP53 mutation is associated with low hypodiploidy, yes or no?
Yes.
18. What are two provisional B-ALL subtypes added?
BCR-ABL1-like B-ALL and B-ALL with iAMP21.
19. What is BCR-ABL1 like B-ALL?
B-ALL with abnormalities involving tyrosine kinases or cytokine receptors.
Involving many different genes: ABL1 (with partners other than BCR), ABL2, PDGFRB, NTRK3, TYK2, CSF1R, and JAK2. Over 30 different partner genes have been described. Some patients have shown remarkable responses to TKI therapy.
Commonly associated with CRLF2 rearrangement, JAK mutation and IKZF1 deletion.
20. Does indolent T-lymphoblastic proliferation exist?
Yes. It was briefly mentioned in the 4th WHO edition, is now a more readily recognized non-neoplastic entity that may mimic T lymphoblastic lymphoma. It typically involves lymphoid tissue of the upper aerodigestive tract but may occur in other locations. Local recurrences are common and systemic dissemination is rare. Histologic examination of involved lymph nodes shows infiltration and sometimes replacement by proliferations of lymphoblasts that are less cytologically atypical than the usual T-lymphoblastic lymphoma. Although the blasts have an immature thymic phenotype that can be demonstrated by TdT staining in lymph nodes, the phenotype reflects a developmentally normal, non-aberrant phenotype and the proliferations are not clonal. These latter features allow this indolent entity to be distinguished from T-lymphoblastic lymphoma.
22. Early T-precursor (ETP) ALL leukemia is added as a provisional new entity. What is its defining phenotype?
By definition, blasts in ETP ALL express CD7 but lack CD1a and CD8, and are positive for 1 or more of the myeloid/stem cell markers CD34, CD117, HLA DR, CD13, CD33, CD11b, or CD65. They typically also express CD2 and cytoplasmic CD3 and may express CD4, but these are not part of the definition. CD5 is often negative and when positive is present on <75% of the blast population.
The unique immunophenotypic and genetic makeup indicate only limited early T-cell differentiation, with retention of some myeloid and stem cell characteristics at both the immunophenotypic and genetic level. Myeloid associated gene mutations, such as FLT3, NRAS/KRAS, DNMT3A, IDH1, and IDH2, are reported at high frequency in ETP ALL, whereas more typical T-ALL–associated mutations such as activating mutations in NOTCH1 or mutations in CDKN1/2 are infrequent. Although initial small series of ETP ALL suggested that outcome was very poor, in the largest series to date, no prognostic significance was found. Caution should be paid to avoid misdiagnosis as T/myeloid MPAL.
23. What is “low count” monoclonal B-cell lymphocytosis?
<0.5 x 109/L PB CLL cells. It is significantly different from CLL.
Tissue-based MBL: lymph nodes, no proliferation centers, adenopathy <1.5 cm based on CT.
24. Which mutation is commonly associated with hairy cell leukemia?
BRAF V600E mutations
25. Which mutation is commonly associated with lymphoplasmacytic lymphoma (LPL)?
MYD88 L265P mutation.
26. Is in situ follicular lymphoma changed to in situ follicular neoplasia (ISFN)? Why?
Yes. Have a low rate of progression, but are more often associated with prior or synchronous overt lymphomas, thus requiring additional clinical assessment.
27. Is pediatric follicular lymphoma (FL) changed to pediatric-type FL, a real entity now?
Yes. Name change is because similar lymphomas may occur in young and rarely in older adults. It is a nodal disease characterized by large expansile highly proliferative follicles that often have prominent blastoid follicular center cells rather than classic centroblasts (or centrocytes). BCL2 rearrangements must not be present, but there may be some BCL2 protein expression. No BCL6 and MYC rearrangement. Usually no treatment except excision.
28. Is large B-cell lymphoma with IRF4 rearrangement (a new provisional entity) an aggressive high grade lymphoma?
No. More aggressive than other pediatric-type FL, but do very well when treated.
It is usually localized disease, often involves cervical lymph nodes or Waldeyer ring, and occurs most commonly in children and young adults. Low stage. They may have a follicular, follicular and diffuse, or pure diffuse growth pattern resembling FL grade 3B or a DLBCL. Strong IRF4/MUM1 expression is seen usually with BCL6 and a high proliferative fraction. BCL2 and CD10 are also expressed in more than half of the cases. Most often of germinal center type, particularly based on gene expression profiling (GEP) studies. Most cases have IG/IRF4 rearrangements sometimes together with BCL6 rearrangements but lack BCL2 rearrangements.
29. What are the features of duodenal-type FL?
Localized overt low-grade FL, distinct from other GI tract FL, many features that overlap with ISFN as well as some features resembling an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Localized process with low risk for dissemination. These patients appear to have an excellent outcome, including some cases managed with a watch-and-wait strategy.
30. Two subtypes of mantle cell lymphoma are recognized. What are they?
Unmutated/minimally mutated IGHV and mostly SOX11+, nodal or tissue mass.
Mutated IGHV and mostly SOX11(-) (indolent leukemic nonnodal MCL with PB, bone marrow (BM), splenic involvement)
31. What is in situ mantle cell neoplasia?
In situ mantle cell neoplasia (ISMCN), new name for in situ MCL, reflecting low clinical risk, is characterized by the presence of cyclin D1+ cells, most typically in the inner mantle zones of follicles, in lymphoid tissues that do not otherwise suggest the diagnosis of a MCL, and is often found incidentally, sometimes in association with other lymphomas.
32. What is MYC/BCL2 “double-expressor” lymphoma?
DLBCL with concomitant expression of MYC/BCL2, but do not carry MYC/BCL2 chromosomal alterations.
Most studies use a cutoff of 40% MYC-expressing cells to define these cases; the cutoff for BCL2 expression 50% is recommended. In several but not all studies, the double-expressor lymphomas have a worse outcome than other DLBCL, NOS but they are not as aggressive as the HGBL, with rearrangements of MYC and BCL2 and/or BCL6.
33. EBV+ DLBCL, NOS replaces EBV+ DLBCL of the elderly(>50 yo). True or false?
True. Because it may occur in younger patients. • Does not include EBV+ B-cell lymphomas that can be given a more specific diagnosis.
34. What is EBV+ mucocutaneous ulcer?
Newly recognized provisional entity associated with iatrogenic immunosuppression or age-related immunosenescence.
35. What is Burkitt-like lymphoma with 11q aberration?
New provisional entity that closely resembles Burkitt lymphoma but lacks MYC rearrangement. Instead, they have a chromosome 11q alteration characterized by proximal gains and telomeric losses. Compared with BL, these lymphomas have more complex karyotypes, lower levels of MYC expression, a certain degree of cytological pleomorphism, occasionally a follicular pattern, and frequently a nodal presentation. The clinical course seems to be similar to BL, but the number of cases reported is still limited.
36. The old “B-cell lymphoma, unclassifiable,with features intermediate between DLBCL and BL” (BCLU ) will not exist anymore. True or false?
True. It is designated as High-grade B-cell lymphoma (HGBL), with MYC and BCL2 and/or BCL6 rearrangements (“double-/triple-hit” lymphomas).
High-grade B-cell lymphoma, NOS includes blastoid-appearing large B-cell lymphomas and cases lacking MYC and BCL2 or BCL6 translocations that would formerly have been called BCLU.
37. Systemic EBV+ T-cell lymphoma of childhood replaces old name of EBV+ T-cell lymphoproliferative disorder of childhood”. True or false?
True. The change is due to its fulminant clinical course and desire to clearly distinguish it from chronic active EBV infection.
38. Hydroa vacciniforme–like lymphoproliferative disorder replaces the old name of “Hydroa vacciniforme–like lymphoma”. True or false?
True. The changes is due to its relationship with chronic active EBV infection and a spectrum in terms of its clinical course.
39. Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) replaces formerly type II EATL. True or false?
True. The change is due to its distinctive nature and lack of association with celiac disease. MEITL is monomorphic, and usually positive for CD8, CD56, and MATK -Gains in chromosome 8q24 involving MYC are seen in a high proportion of cases. - Many cases of MEITL are derived from γδ T cells.
40. What is indolent T-cell lymphoproliferative disorder of the GI tract?
New provisional entity with superficial monoclonal intestinal T-cell infiltrate, usually composed of CD8+ T cells, with an indolent clinical course, some cases show progression. Their optimal management is not yet determined.
41. Primary cutaneous CD4+ small/medium T-cell lymphoma (WHO 2008) is no longer to be diagnosed as an overt lymphoma, and is called lymphoproliferative disorder due to limited clinical risk, localized disease, and similarity to clonal drug reactions. True or false?
True.
42. What is nodal T-cell lymphomas with T-follicular helper (TFH) phenotype?
It is a category created to highlight the spectrum of nodal lymphomas with a TFH phenotype including angioimmunoblastic T-cell lymphoma, follicular T-cell lymphoma, and other nodal PTCL with a TFH phenotype (specific diagnoses to be used due to clinicopathologic differences).
T follicular helper (TFH) phenotype: the neoplastic cells should express at least 2 or 3 TFH related antigens, including CD279/PD1, CD10, BCL6, CXCL13, ICOS, SAP, and CCR5.
43. What is new about ALK(-) anaplastic large-cell lymphoma?
Now a definite entity. GEP studies have shown that ALK- ALCL has a signature quite close to that of ALK+ ALCL and distinct from other NK/TCLs. More recent studies illuminating the genetic landscape of ALK- ALCL have shown convergent mutations and kinase fusions that lead to constitutive activation of the JAK/STAT3 pathway.
A subset with 6p25 rearrangements at IRF4/DUSP22 locus tends to be relatively monomorphic, usually lack cytotoxic granules, and have been reported to have a superior prognosis, - A small subset with TP63 rearrangements are very aggressive.
44. What is breast implant–associated anaplastic large cell lymphoma?
New provisional entity distinguished from other ALK(-) ALCL; noninvasive disease associated with excellent outcome.
Presents as an accumulation of seroma fluid between the implant itself and the surrounding fibrous capsule. Both saline- and silicone-filled implants have been implicated, with a median interval from the time of the implant to the lymphoma of about 10 years. In most cases, the neoplastic cells are confined to the seroma fluid, without invasion of the capsule. In such cases, conservative management is recommended, with removal of the implant and capsule. If there is invasion through the capsule, there is risk of lymph node involvement and systemic spread, warranting systemic chemotherapy.
45. What is new about nodular lymphocyte–predominant Hodgkin lymphoma ?
Variant growth patterns, if present, should be noted in diagnostic report, due to their clinicopathologic associations. Cases associated with synchronous or subsequent sites that are indistinguishable from T-cell histiocyte-rich large B-cell lymphoma (THRLBCL) without a nodular component (lacking any follicular dendritic cells) should be designated THRLBCL-like transformation of NLPHL. Progression to a process with features of THRLBCL is associated with a more aggressive clinical course, and requires different management, such that the term NLPHL in this setting may not be sufficient.
46. What is the diagnostic criteria for accelerated phase of CML?
Any one or more of the followings:
Persistent or increasing WBC (>10 x 109/L), unresponsive to therapy
Persistent or increasing splenomegaly, unresponsive to therapy
Persistent thrombocytosis (>1000 x 109/L), unresponsive to therapy
Persistent thrombocytopenia (<100 x 109/L) unrelated to therapy
20% or more basophils in the PB
10%-19% blasts in the PB and/or BM
Additional clonal chromosomal abnormalities in Ph+ cells at diagnosis that include “major route” abnormalities (second Ph, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype, or abnormalities of 3q26.2
Any new clonal chromosomal abnormality in Ph+ cells that occurs during therapy “Provisional” response-to-TKI criteria
Hematologic resistance to the first TKI (or failure to achieve a complete hematologic response to the first TKI)
Or any hematological, cytogenetic, or molecular indications of resistance to 2 sequential TKIs or therapy
Occurrence of 2 or more mutations in BCR-ABL1 during TKI therapy
Swerdlow S. Elias Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016; 127(20):2375-2390
- Is mastocytosis separated from MPNs?
2. Which gene mutation is strongly associated with chronic neutrophilic leukemia (CNL)?
CSF3R.
3. What is the new subtype (cytogenetic abnormality) in myeloid/lymphoid neoplasms associated with eosinophilia?
PCM1-JAK2: t(8;9)(p22;p24.1) (provisional).
May respond to JAK2 inhibitors.
Bone marrow shows left-shifted erythroid predominance, lymphoid aggregates and myelofibrosis.
4. Is refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T, a provisional entity within the MDS/MPN unclassifiable group) now termed MDS/MPN with ring sideroblasts and thrombocytosis, a real entity?
Yes. Presence of a SF3B1 mutation or, in the absence of SF3B1 mutation, no history of recent cytotoxic or growth factor therapy that could explain the myelodysplastic /myeloproliferative features
5. Which gene mutations are commonly associated with aCML?
SETBP1 and/or ETNK1 mutations in up to a third of cases
6. Is the name of chronic myelogenous leukemia changed to chronic myeloid leukemia?
Yes.
7. Which new gene mutation is added to the diagnostic criteria for juvenile myelomonocytic leukemia (JMML)?
CBL, germline mutation and LOH
8. Is splenomegaly required for the diagnosis of JMML?
Yes.
9. Terminology change in MDS: “refractory anemia” or “refractory cytopenia” has been replaced by “myelodysplastic syndrome” followed by the appropriate modifiers: single vs multilineage dysplasia, ring sideroblasts, excess blasts, or the del(5q) cytogenetic abnormality. True or false?
True.
10. Childhood MDS has been changes. True or false?
False. There are no changes to childhood MDS; refractory cytopenia of childhood remains as a provisional entity within this category.
11. Erythroid/myeloid leukemia does not exist anymore. True or false?
True. There is a major change in the diagnostic criteria for acute erythroid leukemia (erythroid precursors >50% of all BM cells). In the updated classification, the denominator used for calculating blast percentage is all nucleated BM cells, not just the “non-erythroid cells.” The subcategory of acute erythroid leukemia, erythroid/myeloid type (previously defined as a case with >50% BM erythroid precursors and >20% myeloblasts among non-erythroid cells) has been removed from the AML category, and classified to MDS (mostly with excess blasts). Pure erythroid leukemia remains as an AML, NOS subtype and is now the only type of acute erythroid leukemia (>80% immature erythroid precursors with >30% proerythroblasts)
12. May the entity MDS with isolated del(5q) be diagnosed with one additional cytogenetic abnormality except monosomy 7 or del(7q)?
Yes.
13. CHIP can be seen in a healthy person. What does CHIP mean?
Clonal hematopoiesis of indeterminate potential.
Although some patients with CHIP subsequently develop MDS, the natural history of this condition is not yet fully understood; thus, the presence of MDS-associated somatic mutations alone is not considered diagnostic of MDS in this classification, even in a patient with unexplained cytopenia.
14. If an SF3B1 mutation is identified, a diagnosis of MDS-RS may be made even if ring sideroblasts comprise less than 15% of erythroblasts, True or false?
True.
15. Is AML with BCR-ABL1 a new provisional entity?
Yes.
16. Is AML with mutated RUNX1 a new provisional entity?
Yes.
17. B-ALL in germline TP53 mutation is associated with low hypodiploidy, yes or no?
Yes.
18. What are two provisional B-ALL subtypes added?
BCR-ABL1-like B-ALL and B-ALL with iAMP21.
19. What is BCR-ABL1 like B-ALL?
B-ALL with abnormalities involving tyrosine kinases or cytokine receptors.
Involving many different genes: ABL1 (with partners other than BCR), ABL2, PDGFRB, NTRK3, TYK2, CSF1R, and JAK2. Over 30 different partner genes have been described. Some patients have shown remarkable responses to TKI therapy.
Commonly associated with CRLF2 rearrangement, JAK mutation and IKZF1 deletion.
20. Does indolent T-lymphoblastic proliferation exist?
Yes. It was briefly mentioned in the 4th WHO edition, is now a more readily recognized non-neoplastic entity that may mimic T lymphoblastic lymphoma. It typically involves lymphoid tissue of the upper aerodigestive tract but may occur in other locations. Local recurrences are common and systemic dissemination is rare. Histologic examination of involved lymph nodes shows infiltration and sometimes replacement by proliferations of lymphoblasts that are less cytologically atypical than the usual T-lymphoblastic lymphoma. Although the blasts have an immature thymic phenotype that can be demonstrated by TdT staining in lymph nodes, the phenotype reflects a developmentally normal, non-aberrant phenotype and the proliferations are not clonal. These latter features allow this indolent entity to be distinguished from T-lymphoblastic lymphoma.
22. Early T-precursor (ETP) ALL leukemia is added as a provisional new entity. What is its defining phenotype?
By definition, blasts in ETP ALL express CD7 but lack CD1a and CD8, and are positive for 1 or more of the myeloid/stem cell markers CD34, CD117, HLA DR, CD13, CD33, CD11b, or CD65. They typically also express CD2 and cytoplasmic CD3 and may express CD4, but these are not part of the definition. CD5 is often negative and when positive is present on <75% of the blast population.
The unique immunophenotypic and genetic makeup indicate only limited early T-cell differentiation, with retention of some myeloid and stem cell characteristics at both the immunophenotypic and genetic level. Myeloid associated gene mutations, such as FLT3, NRAS/KRAS, DNMT3A, IDH1, and IDH2, are reported at high frequency in ETP ALL, whereas more typical T-ALL–associated mutations such as activating mutations in NOTCH1 or mutations in CDKN1/2 are infrequent. Although initial small series of ETP ALL suggested that outcome was very poor, in the largest series to date, no prognostic significance was found. Caution should be paid to avoid misdiagnosis as T/myeloid MPAL.
23. What is “low count” monoclonal B-cell lymphocytosis?
<0.5 x 109/L PB CLL cells. It is significantly different from CLL.
Tissue-based MBL: lymph nodes, no proliferation centers, adenopathy <1.5 cm based on CT.
24. Which mutation is commonly associated with hairy cell leukemia?
BRAF V600E mutations
25. Which mutation is commonly associated with lymphoplasmacytic lymphoma (LPL)?
MYD88 L265P mutation.
26. Is in situ follicular lymphoma changed to in situ follicular neoplasia (ISFN)? Why?
Yes. Have a low rate of progression, but are more often associated with prior or synchronous overt lymphomas, thus requiring additional clinical assessment.
27. Is pediatric follicular lymphoma (FL) changed to pediatric-type FL, a real entity now?
Yes. Name change is because similar lymphomas may occur in young and rarely in older adults. It is a nodal disease characterized by large expansile highly proliferative follicles that often have prominent blastoid follicular center cells rather than classic centroblasts (or centrocytes). BCL2 rearrangements must not be present, but there may be some BCL2 protein expression. No BCL6 and MYC rearrangement. Usually no treatment except excision.
28. Is large B-cell lymphoma with IRF4 rearrangement (a new provisional entity) an aggressive high grade lymphoma?
No. More aggressive than other pediatric-type FL, but do very well when treated.
It is usually localized disease, often involves cervical lymph nodes or Waldeyer ring, and occurs most commonly in children and young adults. Low stage. They may have a follicular, follicular and diffuse, or pure diffuse growth pattern resembling FL grade 3B or a DLBCL. Strong IRF4/MUM1 expression is seen usually with BCL6 and a high proliferative fraction. BCL2 and CD10 are also expressed in more than half of the cases. Most often of germinal center type, particularly based on gene expression profiling (GEP) studies. Most cases have IG/IRF4 rearrangements sometimes together with BCL6 rearrangements but lack BCL2 rearrangements.
29. What are the features of duodenal-type FL?
Localized overt low-grade FL, distinct from other GI tract FL, many features that overlap with ISFN as well as some features resembling an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Localized process with low risk for dissemination. These patients appear to have an excellent outcome, including some cases managed with a watch-and-wait strategy.
30. Two subtypes of mantle cell lymphoma are recognized. What are they?
Unmutated/minimally mutated IGHV and mostly SOX11+, nodal or tissue mass.
Mutated IGHV and mostly SOX11(-) (indolent leukemic nonnodal MCL with PB, bone marrow (BM), splenic involvement)
31. What is in situ mantle cell neoplasia?
In situ mantle cell neoplasia (ISMCN), new name for in situ MCL, reflecting low clinical risk, is characterized by the presence of cyclin D1+ cells, most typically in the inner mantle zones of follicles, in lymphoid tissues that do not otherwise suggest the diagnosis of a MCL, and is often found incidentally, sometimes in association with other lymphomas.
32. What is MYC/BCL2 “double-expressor” lymphoma?
DLBCL with concomitant expression of MYC/BCL2, but do not carry MYC/BCL2 chromosomal alterations.
Most studies use a cutoff of 40% MYC-expressing cells to define these cases; the cutoff for BCL2 expression 50% is recommended. In several but not all studies, the double-expressor lymphomas have a worse outcome than other DLBCL, NOS but they are not as aggressive as the HGBL, with rearrangements of MYC and BCL2 and/or BCL6.
33. EBV+ DLBCL, NOS replaces EBV+ DLBCL of the elderly(>50 yo). True or false?
True. Because it may occur in younger patients. • Does not include EBV+ B-cell lymphomas that can be given a more specific diagnosis.
34. What is EBV+ mucocutaneous ulcer?
Newly recognized provisional entity associated with iatrogenic immunosuppression or age-related immunosenescence.
35. What is Burkitt-like lymphoma with 11q aberration?
New provisional entity that closely resembles Burkitt lymphoma but lacks MYC rearrangement. Instead, they have a chromosome 11q alteration characterized by proximal gains and telomeric losses. Compared with BL, these lymphomas have more complex karyotypes, lower levels of MYC expression, a certain degree of cytological pleomorphism, occasionally a follicular pattern, and frequently a nodal presentation. The clinical course seems to be similar to BL, but the number of cases reported is still limited.
36. The old “B-cell lymphoma, unclassifiable,with features intermediate between DLBCL and BL” (BCLU ) will not exist anymore. True or false?
True. It is designated as High-grade B-cell lymphoma (HGBL), with MYC and BCL2 and/or BCL6 rearrangements (“double-/triple-hit” lymphomas).
High-grade B-cell lymphoma, NOS includes blastoid-appearing large B-cell lymphomas and cases lacking MYC and BCL2 or BCL6 translocations that would formerly have been called BCLU.
37. Systemic EBV+ T-cell lymphoma of childhood replaces old name of EBV+ T-cell lymphoproliferative disorder of childhood”. True or false?
True. The change is due to its fulminant clinical course and desire to clearly distinguish it from chronic active EBV infection.
38. Hydroa vacciniforme–like lymphoproliferative disorder replaces the old name of “Hydroa vacciniforme–like lymphoma”. True or false?
True. The changes is due to its relationship with chronic active EBV infection and a spectrum in terms of its clinical course.
39. Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) replaces formerly type II EATL. True or false?
True. The change is due to its distinctive nature and lack of association with celiac disease. MEITL is monomorphic, and usually positive for CD8, CD56, and MATK -Gains in chromosome 8q24 involving MYC are seen in a high proportion of cases. - Many cases of MEITL are derived from γδ T cells.
40. What is indolent T-cell lymphoproliferative disorder of the GI tract?
New provisional entity with superficial monoclonal intestinal T-cell infiltrate, usually composed of CD8+ T cells, with an indolent clinical course, some cases show progression. Their optimal management is not yet determined.
41. Primary cutaneous CD4+ small/medium T-cell lymphoma (WHO 2008) is no longer to be diagnosed as an overt lymphoma, and is called lymphoproliferative disorder due to limited clinical risk, localized disease, and similarity to clonal drug reactions. True or false?
True.
42. What is nodal T-cell lymphomas with T-follicular helper (TFH) phenotype?
It is a category created to highlight the spectrum of nodal lymphomas with a TFH phenotype including angioimmunoblastic T-cell lymphoma, follicular T-cell lymphoma, and other nodal PTCL with a TFH phenotype (specific diagnoses to be used due to clinicopathologic differences).
T follicular helper (TFH) phenotype: the neoplastic cells should express at least 2 or 3 TFH related antigens, including CD279/PD1, CD10, BCL6, CXCL13, ICOS, SAP, and CCR5.
43. What is new about ALK(-) anaplastic large-cell lymphoma?
Now a definite entity. GEP studies have shown that ALK- ALCL has a signature quite close to that of ALK+ ALCL and distinct from other NK/TCLs. More recent studies illuminating the genetic landscape of ALK- ALCL have shown convergent mutations and kinase fusions that lead to constitutive activation of the JAK/STAT3 pathway.
A subset with 6p25 rearrangements at IRF4/DUSP22 locus tends to be relatively monomorphic, usually lack cytotoxic granules, and have been reported to have a superior prognosis, - A small subset with TP63 rearrangements are very aggressive.
44. What is breast implant–associated anaplastic large cell lymphoma?
New provisional entity distinguished from other ALK(-) ALCL; noninvasive disease associated with excellent outcome.
Presents as an accumulation of seroma fluid between the implant itself and the surrounding fibrous capsule. Both saline- and silicone-filled implants have been implicated, with a median interval from the time of the implant to the lymphoma of about 10 years. In most cases, the neoplastic cells are confined to the seroma fluid, without invasion of the capsule. In such cases, conservative management is recommended, with removal of the implant and capsule. If there is invasion through the capsule, there is risk of lymph node involvement and systemic spread, warranting systemic chemotherapy.
45. What is new about nodular lymphocyte–predominant Hodgkin lymphoma ?
Variant growth patterns, if present, should be noted in diagnostic report, due to their clinicopathologic associations. Cases associated with synchronous or subsequent sites that are indistinguishable from T-cell histiocyte-rich large B-cell lymphoma (THRLBCL) without a nodular component (lacking any follicular dendritic cells) should be designated THRLBCL-like transformation of NLPHL. Progression to a process with features of THRLBCL is associated with a more aggressive clinical course, and requires different management, such that the term NLPHL in this setting may not be sufficient.
46. What is the diagnostic criteria for accelerated phase of CML?
Any one or more of the followings:
Persistent or increasing WBC (>10 x 109/L), unresponsive to therapy
Persistent or increasing splenomegaly, unresponsive to therapy
Persistent thrombocytosis (>1000 x 109/L), unresponsive to therapy
Persistent thrombocytopenia (<100 x 109/L) unrelated to therapy
20% or more basophils in the PB
10%-19% blasts in the PB and/or BM
Additional clonal chromosomal abnormalities in Ph+ cells at diagnosis that include “major route” abnormalities (second Ph, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype, or abnormalities of 3q26.2
Any new clonal chromosomal abnormality in Ph+ cells that occurs during therapy “Provisional” response-to-TKI criteria
Hematologic resistance to the first TKI (or failure to achieve a complete hematologic response to the first TKI)
Or any hematological, cytogenetic, or molecular indications of resistance to 2 sequential TKIs or therapy
Occurrence of 2 or more mutations in BCR-ABL1 during TKI therapy