Recent advances in cutaneous lymphoma-implications for current and future classifications.

The Revised European-American Classification of mature lymphoid neoplasms published in 1994 and the 2001, 2008 and 2016 WHO classifications that followed, were the product of international collaboration and consensus amongst haematopathologists, geneticists, molecular scientists and clinicians. Primary cutaneous lymphomas were fully incorporated into this process following the publication of the WHO-EORTC classification of cutaneous lymphomas in 2005. The definition, diagnostic criteria and recommended studies for primary cutaneous lymphoma continue to be refined. The 2022 International Consensus Classification represents the most recent update and an overview of all the main entities presenting primarily in the skin, together with the major changes in classification, are summarized herein. Primary cutaneous marginal zone lymphoma is segregated from other extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma) and downgraded to a lymphoproliferative disorder in line with its markedly indolent behaviour. In addition, two subtypes are recognised, based largely but not exclusively on whether they are heavy chain class-switched or IgM positive. Similarly, in keeping with a trend to greater conservatism, primary cutaneous acral CD8 positive T cell lymphoma is now also classified as a lymphoproliferative disorder. In addition, significant new insights into the biology of primary cutaneous lymphoma have also recently been forthcoming and will be presented. These studies have enhanced our knowledge of genetic, epigenetic and transcriptional changes in this group of diseases. They not only identify potential targets for novel therapies, but also raise as yet unanswered questions as to how we categorise cutaneous lymphomas, particularly with respect to relationships with similar lymphomas at extracutaneous sites.

Natural killer cell (NK) subsets and NK-like T-cell populations in acute myeloid leukemias and myelodysplastic syndromes.

The impact of the immune microenvironment on the behavior and therapeutic strategies for hematopoietic and lymphoid neoplasms is being increasingly recognized. Many functional studies of natural killer (NK) cell cytotoxic responses in myelodysplasia (MDS) and acute myeloid leukemia (AML) exist, but with limited data on these lymphocyte proportions and related T-cell subsets. The proportions of these cells and their prognostic implications were therefore investigated in 89 AML, 51 MDS, and 20 control marrows by flow cytometry. The median proportion of NK cells (relative to the total lymphocytes) was lower in AML versus controls (P = 0.01). Among AML, a lower proportion of NK cells predicted better survival, whereas a higher NK cell proportion was associated with the poor prognostic AML category (P = 0.002). NK cell proportions were similar in MDS, MDS subgroups, and control marrows. The relative proportion of the mature NK cell subset (CD56(dim) CD16/57(bright) ) was lower in AML and MDS versus controls (P = 0.006, P = 0.0002, respectively). The proportion of mature NK cells was not a prognostic indicator although fewer were seen in poor prognosis AML. In contrast, a lower proportion of mature NK cells correlated with worse survival in MDS (P = 0.027). A higher proportion of NK-like T-cells (of total lymphoid cells) was found in MDS compared to controls (P = 0.01). A lower proportion of NK-like T-cells predicted better survival in AML but not in MDS. Thus, the proportions of NK, NK-cell subsets, and NK-like T-cells vary in myeloid neoplasms, may potentially impact immunomodulatory therapies, and may impact outcome. © 2016 International Clinical Cytometry Society.

Radioisotopic localization of (90)Yttrium-ibritumomab tiuxetan in patients with CD20+ non-Hodgkin's lymphoma.

PURPOSE: (90)Yttrium-ibritumomab-tiuxetan (Zevalin) is an effective treatment for relapsed or refractory low-grade, follicular, or transformed B-cell NHL. The purpose of this study is to assess whether tissue and cellular localization of (90)Y-ibritumomab-tiuxetan determined by autoradiography and radioactivity localized to tumor tissue might enhance our understanding of the mechanism of action of radioimmunotherapy. METHODS: Eight eligible patients had CD20+ NHL, a bulky peripheral lymph node, and were scheduled for (90)Y-ibritumomab-tiuxetan treatment. 2-Deoxy-2-[F-18]fluoro-D: -glucose-positron emission tomography/computed tomography (FDG-PET/CT) was performed prior to treatment and at 12 weeks after therapy for assessment of response. Bone marrow, lymph node, and blood samples were collected 114 +/- 3 h after 14.8 MBq/kg (90)Y-ibritumomab-tiuxetan and processed for histology, scintillation counting, and microscopic autoradiography. RESULTS: Pericellular membrane localization of (90)Y-ibritumomab-tiuxetan to lymphoma cells was observed by autoradiography in the involved areas of lymph node with absence of significant localization in histologically normal sections of bone marrow. Pericellular radioactivity and the highest quantitative radioactivity were observed in lymph node samples of responding patients. CONCLUSIONS: (90)Y-ibritumomab-tiuxetan localizes to the surface membrane of CD20+ lymphoma cells in affected lymph nodes. The patients with the highest quantitative concentration of radioactivity to the lymph node as determined by scintillation counting were observed to have a clinical and FDG-PET/CT response.

Update on extranodal lymphomas. Conclusions of the Workshop held by the EAHP and the SH in Thessaloniki, Greece.

Classification and proper treatment of extranodal lymphoma is hindered by the diversity of lymphoma types and the relative rarity of many of these tumour types. In order to review controversial issues in extranodal lymphoma diagnosis, a joint Workshop of the European Haematopathology Association (EAHP) and the Society for Hematopathology (SH) was held, where 99 selected cases were reviewed and discussed. This Workshop summary is focused on the most controversial aspect of cutaneous B-cell lymphoma, other extranodal B-cell lymphomas, plasmablastic lymphoma and anaplastic large-cell lymphoma in extranodal sites, and makes practical recommendations about diagnosis and therapeutic approaches.

Primary pleural effusion posttransplant lymphoproliferative disorder: Distinction from secondary involvement and effusion lymphoma.

Pleural effusion presentation of posttransplant lymphoproliferative disorder (PTLD) is relatively uncommon. Most examples of effusion-based PTLD have been secondary to widespread solid organ involvement, and are associated with an aggressive clinical course. We report on a case of primary effusion PTLD in a 70-yr-old male liver transplant recipient with a history of hepatitis B infection. Cytomorphologically, the pleural fluid specimen showed a monomorphous population of intermediate to large-sized transformed lymphoid cells, with irregular multilobated nuclear contours and readily identifiable mitotic figures. Flow cytometric immunophenotypic studies revealed a CD5-negative, CD10-negative, lambda immunoglobulin light chain-positive, monoclonal B-lymphocyte (CD19-positive/CD20-positive) population. The immunocytochemical stain for CD30 antigen was negative. In situ hybridization study for Epstein-Barr virus (EBV) early RNA (EBER) and Southern blot analysis for EBV terminal repeat sequences were both positive. Southern blot analysis for human herpes virus-8 (HHV-8) was negative. No solid-organ PTLD was identified, and the cytologic results supported the diagnosis of primary effusion PTLD. Immunosuppression was decreased, and 8 mo following the diagnosis of pleural fluid PTLD, the patient was stable and his pleural effusion had markedly diminished. Recognition of primary effusion PTLD and its distinction from PTLD secondarily involving the body fluids and from other lymphomas is important, since the behavior and prognosis appear different.

Is lymphoplasmacytic lymphoma/immunocytoma a distinct entity? A clinicopathologic study of 20 cases.

Lymphoplasmacytic lymphoma/immunocytoma (LLI) was defined initially as a small B-cell lymphoma with plasmacytoid or plasmacytic features. Because other types of small B-cell lymphoma, particularly marginal zone B-cell lymphoma may exhibit plasmacytic differentiation, the revised European-American lymphoma classification and World Health Organization has defined LLI more narrowly to exclude other small B-cell lymphomas. The goal of this study was to reevaluate LLI as a clinicopathologic entity. Twenty cases were selected from 43 previously diagnosed as "small lymphocytic lymphoma, plasmacytoid" or "immunocytoma" from 1985 to 1998. Cases fulfilling the criteria for B-cell small lymphocytic lymphoma, follicular lymphoma, marginal zone B-cell lymphoma, or other types of B-cell lymphoma were excluded. The histopathology and immunoreactivity for CD20, CD79a, CD3, CD43, CD23, CD5, kappa, lambda, and immunoglobulins (Ig's) M, G, and A were reviewed, in addition to available clinical findings. There were 13 men and seven women, with a mean age of 69 years. Five patients had documented Waldenström's macroglobulinemia (WM). Three architectural patterns were observed. Pattern A (seven of 20) showed open sinuses, small follicles, and hemosiderosis; pattern B (four of 20) showed hyperplastic follicles; and pattern C (nine of 20) showed diffuse effacement. Epithelioid histiocytes were prominent in patterns B and C but absent in A. Cytologically, six of 20 were polymorphous with 10% to 40% transformed cells; 14 of 20 were lymphoplasmacytic. Five cases showed minor foci of monocytoid B cells. One case showed a composite histology of LLI and small lymphocytic lymphoma. Amyloid was present in two cases. All cases were CD20 and/or CD79a immunoreactive, with two of 20 positive for CD43. Twelve cases were kappa monoclonal and eight cases were lambda monoclonal. Twelve of 17 cases that could be evaluated were positive for IgM and five were positive for IgG. All cases were negative for CD5 and CD23 with the exception of the one case with a composite histology. Eleven of 20 patients with available follow-up died of disease (median, 48 months), and eight of 20 are alive with disease at a follow-up of 6 months to 2 years. LLI does appear to represent a distinct clinicopathologic entity even though it shows morphologic heterogeneity and overlapping features with marginal zone B-cell lymphoma and small lymphocytic lymphoma. Recognition of LLI is important because the overall prognosis may be worse than for other types of small B-cell lymphomas.

Immunophenotypic and genotypic markers of follicular center cell neoplasia in diffuse large B-cell lymphomas.

Diffuse large B-cell lymphomas (DLBCL) are a biologically and clinically heterogeneous entity. Although some DLBCL represent transformation of follicular lymphomas (FL), the proportion that is of follicular center cell (FCC) origin remains uncertain. Immunophenotypic and genotypic markers used to suggest a FCC origin for a lymphoma (bcl-6 and CD10 expression, lack of CD138 expression, bcl-2 rearrangements [R]) or to subdivide DLBCL (bcl-2 expression, bcl-6 R) were therefore investigated in 22 FL and 44 DLBCL using paraffin section immunostains and Southern blot/polymerase chain reaction analysis. All FL tested were bcl-6+ (19) and CD138- (22) with 16/19 also bcl-2 and CD10+ (classic phenotype), one bcl2+, CD10- (grade III) and two bcl2-, CD10+ (grade II or III). Bcl-2R was identified in 4/5 FL-GrI, 3/6 FL-GrII, and 1/3 FL-GrIII. Bcl-6R was found in 0/5, 2/4, and 0/3 FL, respectively. All but 3/41 DLBCL were bcl-6+ with 17/37 also bcl-2+ and CD10+. Three of these cases were also CD138+. Twelve bcl-6+ cases were bcl-2+, CD10-, six bcl-2-, CD10+, and two bcl-2-, CD10-. The three bcl-6- cases were bcl-2+, CD138- and two were CD10+. Bcl-2R was identified in 5/27 DLBCL with 4/5 bcl-2+, 3/4 tested CD10+ and 4/4 bcl-6+. Bcl-6R was identified in 7/26 including three with a classic FL phenotype. The vast majority of DLBCL in this study have an immunophenotype that supports a FCC origin. Although the proportion of DLBCL that co-expressed bcl-6, CD10 and bcl-2 was lower than for the FL, absence of bcl-2 or CD10 may be associated with higher grade FL It is also possible that bcl-6 expression is not completely specific for a FCC origin. Only a minority of cases suggested postfollicular differentiation. Only a minority of DLBCL show bcl-2R, suggesting that many have a different molecular pathogenesis than most low-grade FL. Bcl-6R did not exclude a FCC origin.

Histological and immunoglobulin VH gene analysis of interfollicular small lymphocytic lymphoma provides evidence for two types.

Interfollicular small lymphocytic lymphoma (I-SLL) has not been well characterized and its relationship to small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) is uncertain. Moreover, two different proliferation center growth patterns have been described with respect to reactive germinal centers. In this study, we evaluate the histological and immunophenotypic features of 13 cases of I-SLL and immunoglobulin heavy chain variable (VH) gene sequences from 10 cases. Immunophenotypic analyses indicate that cases showing either growth pattern have the same CD5-positive B cell phenotype typical of SLL or CLL. Sequence analysis revealed the use of VH, D, and J gene segments often found in CLL, although there may be more frequent use of J6. Similar to recent studies of CLL, there were approximately equal numbers of cases with either mutated or unmutated VH genes without evidence of ongoing mutation, consistent with I-SLL having either a naïve or memory B cell origin. Interestingly, the mutational status of the I-SLL VH genes seemed to correlate with the two different histological growth patterns. These studies support the proposal that I-SLL represents SLL/CLL and suggest the recently proposed two types of CLL originating from either memory or naïve B cells may have different histological patterns of growth in lymph nodes that show architectural preservation.

Classification of small B-cell lymphoid neoplasms using a paraffin section immunohistochemical panel.

Immunophenotypic analysis is critical in categorizing small B-cell neoplasms; however, many recommended antibody panels have required fresh or frozen tissue. Many paraffin-reactive antibodies are now available but have been studied mostly in isolation. Therefore, the utility of a panel of paraffin-reactive antibodies in differentiating small B-cell neoplasms was investigated. Paraffin-embedded sections of small lymphocytic lymphoma/B-chronic lymphocytic leukemia (SLL/B-CLL; 12), mantle cell (MCL; 15), follicular (FL; 11), and marginal zone B-cell (MZL; eight) lymphomas were stained with CD20/L26, CD3, CD43/DF-T1 or Leu22, CD5/4C7, CD23/BU38, cyclin D1/H295, and CD10/56C6 antibodies. For select antibodies, results were compared to flow cytometric data (FC). Formalin and B5 fixation were also compared. Seven of 11 SLL/B-CLL were CD43+ CD5+ CD23+ cyclin D1- CD10-; seven of 11 MCL were CD43+ CD5+ CD23- cyclin D1+ CD10-; nine of 10 FL were CD43- CD5- CD23- cyclin D1- CD10+; and five of six MZL were CD43+ CD5- CD23- cyclin D1- CD10-. CD5, CD23, and CD10 stains showed sensitivities of 81, 88, and 100%, respectively, compared to FC. With B5 fixation, cyclin D1 was more often negative and CD5 more often equivocal. A panel of paraffin-reactive antibodies aids in classification of small B-cell neoplasms, although a small number of cases have indeterminate phenotypes and MZL have no defining features. CD5 separates most SLL/B-CLL and MCL from FL and MZL. CD23 separates SLL/B-CLL from most MCL, but cyclin D1 is most important for identifying MCL. CD10 positivity distinguishes most FL from other small B-cell lymphoid neoplasms.

Salivary gland mucosa-associated lymphoid tissue lymphoma immunoglobulin V(H) genes show frequent use of V1-69 with distinctive CDR3 features.

Salivary gland mucosa associated lymphoid tissue (MALT) type lymphomas are B-cell neoplasms that develop out of a reactive infiltrate, often associated with Sjögren's syndrome. Previous reports from our laboratory involving 10 patients suggested these lymphomas expressed a restricted immunoglobulin (Ig) V(H) gene repertoire with over use of V1-69 gene segments. To better determine the frequency of V1-69 use and whether there may also be selection for CDR3 structures, we sequenced the V(H) genes from 15 additional cases. Over half of the potentially functional V(H) genes (8 of 14) used a V(H)1 family V1-69 gene segment, whereas the other cases used different gene segments from the V(H)1 (V1-46), V(H)3 (V3-7, V3-11, V3-30.3, V3-30.5), and V(H)4 (V4-39) families. The 8 V1-69 V(H) genes used 5 different D segments in various reading frames, but all used a J4 joining segment. The V1-69 CDR3s showed remarkable similarities in lengths (12-14 amino acids) and stretches of 2 to 3 amino acids between the V-D and D-J junctions. They did not resemble CDR3s typical of V1-69 chronic lymphocytic leukemias. This study extends our earlier work in establishing that salivary gland MALT lymphomas represent a highly selected B-cell population. Frequent use of V1-69 appears to differ from MALT lymphomas that develop at other sites. The high degree of CDR3 similarity among the V1-69 cases suggests that different salivary gland lymphomas may bind similar, if not identical epitopes. Although the antigen specificities are presently unknown, similar characteristic CDR3 sequences are often seen with V1-69 encoded antibodies that have anti-IgG or rheumatoid factor activity. (Blood. 2000;95:3878-3884)

Epstein-Barr virus-negative post-transplant lymphoproliferative disorders: a distinct entity?

Post-transplant lymphoproliferative disorders (PTLDs) are usually but not invariably associated with Epstein-Barr virus (EBV). The reported incidence, however, of EBV-negative PTLDs varies widely, and it is uncertain whether they should be considered analogous to EBV-positive PTLDs and whether they have any distinctive features. Therefore, the EBV status of 133 PTLDs from 80 patients was determined using EBV-encoded small ribonucleic acid (EBER) in situ hybridization stains with or without Southern blot EBV terminal repeat analysis. The morphologic, immunophenotypic, genotypic, and clinical features of the EBV-negative PTLDs were reviewed, and selected features were compared with EBV-positive cases. Twenty-one percent of patients had at least one EBV-negative PTLD (14% of biopsies). The initial EBV-negative PTLDs occurred a median of 50 months post-transplantation compared with 10 months for EBV-positive cases. Although only 2% of PTLDs from before 1991 were EBV negative, 23% of subsequent PTLDs were EBV negative (p <0.001). Of the EBV-negative PTLDs, 67% were of monomorphic type (M-PTLD) compared with 42% of EBV-positive cases (p <0.05). The other EBV-negative PTLDs were of infectious mononucleosis-like, plasma cell-rich (n = 2), small B-cell lymphoid neoplasm, large granular lymphocyte disorder (n = 4) and polymorphic (P) types. B-cell clonality was established in 14 specimens and T-cell clonality was established in three (two patients). None of the remaining specimens were studied with Southern blot analysis and some had no ancillary studies. Rearrangement of c-MYC was identified in two M-PTLDs with small noncleaved-like features, and rearrangement of BCL-2 was found in one large noncleaved-like M-PTLD. Ten patients were alive at 3 to 63 months (only three patients received chemotherapy). Seven patients, all with M-PTLDs, are dead at 0.3 to 6 months. Therefore, EBV-negative PTLDs have distinct features, but some do respond to decreased immunosuppression, similar to EBV-positive cases, suggesting that EBV positivity should not be an absolute criterion for the diagnosis of a PTLD.

Hepatosplenic and subcutaneous panniculitis-like gamma/delta T cell lymphomas are derived from different Vdelta subsets of gamma/delta T lymphocytes.

Gamma/delta T cell lymphomas (gamma/delta TCL) represent rare, often aggressive types of T cell malignancy that are clinically and pathologically diverse. Most gamma/delta TCL occur as a hepatosplenic or subcutaneous type. To date, analysis of the T cell receptor delta (TCRS) gene repertoire of hepatosplenic gamma/delta TCL (gamma/delta HSTCL) and subcutaneous panniculitis-like gamma/delta TCL (gamma/delta SPTCL) has been reported only in a limited number of cases. In this study we analyzed 11 gamma/delta HSTCL and 4 gamma/delta SPTCL by polymerase chain reaction and immunostaining to determine their usage of the Vdelta subtypes (Vdelta1-6). It is noteworthy that 10 of 11 gamma/delta HSTCL expressed the Vdelta1 gene. The remaining case also expressed T cell receptor delta (TCRS) as determined by flow cytometry and TCRdelta rearrangement in Southern blot. However, the Vdelta gene expressed by this lymphoma could not be determined, which suggests usage of an as yet unidentified Vdelta gene. In striking contrast to the gamma/delta HSTCL, all 4 gamma/delta SPTCL expressed the Vdelta2 gene. Our data demonstrate that gamma/delta HSTCL are preferentially derived from the Vdelta1 subset of gamma/delta T lymphocytes, whereas gamma/delta SPTCL are preferentially derived from the Vdelta2 subset. The pattern of Vdelta gene expression in HSTCL and SPTCL corresponds to the respective, predominant gamma/delta T cell subsets normally found in the spleen and skin. This finding suggests that gamma/delta TCL are derived from normal gamma/delta T lymphocytes which reside in the affected tissues. Furthermore, the selective, lymphoma type-specific Vdelta gene segment usage may provide a molecular tool to distinguish better among various types of gamma/delta TCL lymphoma particularly in the clinically advanced, widely disseminated cases.

HIV-associated Waldeyer's ring lymphoid hyperplasias: characterization of multinucleated giant cells and the role of Epstein-Barr virus.

Lymphoid hyperplasia of Waldeyer's ring (WR) is an often-symptomatic complication of human immunodeficiency virus (HIV) infection. A characteristic but not well explained finding is the presence of multinucleated giant cells (MNGCs) adjacent to crypt or surface epithelium. To further elucidate the MNGCs and assess their relationship to HIV and Epstein-Barr virus (EBV), 12 specimens from 11 HIV-positive patients were stained with antibodies to HIV-1 p24, EBV (latent membrane protein, LMP-1), histiocytes (CD68), and other antigen-presenting cells: S-100 protein, the Langerhans cell (LC) marker CD1a, and the follicular dendritic cell (FDC) marker (CD21). Double immunofluorescent staining to assess co-expression of p24 and cell-specific markers was performed and analyzed by laser-scanning confocal microscopy with 3-dimensional reconstruction. In situ hybridization for EBV-encoded small RNA (EBER) was performed in all cases. Immunostains showed MNGCs labeled for p24, S-100, and CD68, but not CD1a. In 1 case, rare MNGCs were CD21-positive. EBV LMP-1 was uniformly negative, although EBER-positive lymphocytes were seen by in situ hybridization in 9 of 12 specimens (numerous in only 3 specimens). Double immunofluorescent staining showed co-localization of p24 with CD68 and S-100. Our results suggest that MNGCs are generally HIV-infected, EBV-negative, and most likely represent an unusual S-100-positive histiocyte subset (not LC or FDC). Their exact pathophysiologic role remains uncertain. EBV does not appear to play a major role in the pathogenesis of WR lymphoid hyperplasias in HIV infection.

Small B-cell lymphomas of the lymph nodes and spleen: practical insights to diagnosis and pathogenesis.

As defined in the proposed World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues, the small B-cell lymphomas include B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma, mantle cell lymphoma, follicular lymphoma, marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, nodal marginal zone lymphoma, lymphoplasmacytic lymphoma, and splenic marginal zone B-cell lymphoma. These neoplasms are recognized mostly on the basis of their histopathologic features, but ancillary studies are useful in confirming and sometimes making the diagnosis. Clinically, the small B-cell lymphomas of lymph nodes and spleen (but not those of MALT type) are usually disseminated at diagnosis and considered incurable. With the exception of mantle cell lymphoma, however, they are generally indolent. The small B-cell lymphomas are among the best examples of how malignant lymphomas can be related to the normal immune system. Although uncertainties exist, these lymphomas are generally considered the neoplastic equivalents of normal B-cell compartments. From a molecular perspective, mantle cell and follicular lymphomas are the best characterized. In both cases, there are characteristic chromosomal translocations involving the immunoglobulin heavy chain and the cyclin D1 or bcl-2 genes, respectively, that are probably followed by additional molecular events leading to overt neoplasia. Variable proportions of the small B-cell lymphomas undergo transformation that might be associated with abnormalities in tumor suppressor genes / cell cycle regulatory proteins. After a brief review of normal B-cell development, the major small B-cell lymphomas (except for those of MALT type) will be discussed in terms of their morphologic features, immunophenotype (including paraffin-section immunostaining), genotype, karyotype, and clinical features, including disease evolution.

Subcutaneous panniculitis-like T-cell lymphoma: clinicopathologic, immunophenotypic, and genotypic analysis of alpha/beta and gamma/delta subtypes.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon cutaneous lymphoma that has been proposed as a distinct clinicopathologic entity, but studies of SPTCL are limited. We studied the clinicopathologic, immunophenotypic, and genetic features of 11 SPTCLs. All cases had a variable admixture of pleomorphic small, medium, or large lymphocytes and histiocytes infiltrating the subcutis in a lobular panniculitis-like pattern. A granulomatous reaction was seen in three cases and erythrophagocytosis in four. Karyorrhexis and fat necrosis were present in all cases. Angioinvasion was seen in seven SPTCLs; four had areas of coagulation necrosis. All cases expressed T-cell-associated antigens (CD3epsilon, CD45RO, or CD43) and T-cell receptors (TCR); nine expressed alphabeta TCRs and two expressed gammadelta TCRs. T-cell receptor-gamma, TCRbeta, or TCRdelta genes were clonally rearranged in 8 of 10 cases studied. Both gammadelta SPTCLs expressed Vdelta2+ TCRs and were CD4-, CD8- and CD56+. CD56 was negative in seven of nine alphabeta SPTCLs and inconclusive in the other two. Six of nine alphabeta SPTCLs were CD8+; the CD4/CD8 phenotypes were indeterminate in the other three. Cytolytic granule-associated proteins were expressed by all SPTCLs (11 of 11 were TIA-1+, 4 of 4 were perforin+). In situ hybridization for Epstein-Barr virus-encoded RNA (EBER-1) was negative in all cases. Most patients responded to systemic chemotherapy or local radiation therapy. Seven patients are alive: four without disease (19-73 months) and three with disease (32-72 months); four died: three of disease (3-25 months) and one without disease (42 months). We conclude that SPTCLs are clonal, EBV-, cytotoxic T-cell lymphomas derived from alphabeta T-cells or gammadelta T-cells. The gammadelta SPTCLs appear to be preferentially derived from the Vdelta2+ subset. Subcutaneous panniculitis-like T-cell lymphoma may be rapidly fatal or indolent; local therapy may be appropriate for some patients.

A near-haploid bone marrow karyotype in systemic mast cell disease: is it characteristic of the disease or an incidental finding?

We present the case of a 40-year-old man with aggressive systemic mast cell disease. The patient had a predominant near-haploid clone in his bone marrow cells, detected by cytogenetic analysis performed at the time of diagnosis. The similarities between this case and a previously published case of near-haploidy in a patient with malignant mastocytosis suggest that near-haploidy may be a characteristic of aggressive systemic mast cell disease rather than an incidental finding.