Immunoreactivity of CD99 in non-Hodgkin's lymphoma: unexpected frequent expression in ALK-positive anaplastic large cell lymphoma

To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified.     

MUC1 (EMA) is preferentially expressed by ALK positive anaplastic large cell lymphoma, in the normally glycosylated or only partly hypoglycosylated form.

AIMS: To investigate whether MUC1 mucin, a high molecular weight transmembrane glycoprotein, also known as epithelial membrane antigen (EMA), differs in its expression and degree of glycosylation between anaplastic large cell lymphoma (ALCL) and classic Hodgkin's disease (HD), and whether MUC1 immunostaining can be used to differentiate between CD30 positive large cell lymphomas. METHODS/RESULTS: Using five different monoclonal antibodies (E29/anti-EMA, DF3, 139H2, VU-4H5, and SM3) that distinguish between various MUC1 glycoforms, high MUC1 expression (50-95% of tumour cells positive) was found in 13 of 17 anaplastic lymphoma kinase (ALK) positive systemic nodal ALCLs, and in one of 20 cases of classic HD. Scattered or focal staining (< 25% of tumour cells) was seen in two additional ALK positive systemic ALCLs, two additional classic HD cases, and in three of 20 cases of ALK negative systemic nodal ALCL. Primary cutaneous ALCL showed no staining with the anti-MUC1 antibodies. Antibodies detecting hypoglycosylated MUC1 were found to be absent in all lymphomas (SM3) or present in only six of 15 ALK positive ALCLs (VU-4H5). CONCLUSIONS: MUC1 is preferentially expressed by a subtype of systemic nodal ALCL, characterised by ALK expression, but is found in only a few cases of classic HD and ALK negative ALCL. Therefore, although MUC1 could be used in a panel of markers for CD30 positive lymphomas, it is probably not a valuable tool to differentiate between ALK negative CD30 positive large cell lymphomas. Finally, the degree of MUC1 glycosylation in lymphomas is relatively high, compared with the aberrant hypoglycosylation found in adenocarcinomas.     

Epstein-Barr virus association and ALK gene expression in anaplastic large-cell lymphoma

Anaplastic large cell lymphoma of T/null-cell type (ALCL) is associated with a characteristic genetic abnormality t(2;5) that results in the NPM-ALK chimeric gene and the protein product derived thereof. In 10% to 20% of ALCLs, the translocation partners of the ALK gene are genes other than NPM (variant translocations). ALK gene expression limited to the cytoplasm implies a variant translocation. In this study, we have investigated 46 cases of ALCL for expression and localization of ALK protein and its association with Epstein-Barr virus (EBV) (by hybridization to EBV-encoded nuclear RNA-1 [EBER-1] and immunostaining for LMP-1). ALCL patients with a null cell phenotype were significantly younger as compared with those of T-cell phenotype (mean age: 28 years v 42 years; P =.018). Sixteen of 46 ALCL cases (34%) were ALK positive. ALK-positive patients were significantly younger (mean age: 25 years for those with both cytoplasmic and nuclear staining; 22 years for those with exclusive cytoplasmic staining; and 41 years for those negative for the ALK gene; P =.023). EBER-1 was detected in 9 of 46 cases (20%), and LMP-1 expression was noted in 5 of them. By polymerase chain reaction analysis, all EBV-associated cases that were investigated showed type I EBV. Whereas 2 of 23 T-cell ALCLs (9%) were EBER-1+, and 7 of 23 null-cell ALCLs (30%) showed EBV association (P =.057). EBV association was seen in 20% of ALK-negative cases, in 0% of cases with ALK gene expression in both nucleus and cytoplasm, and in 60% of cases with ALK gene expression exclusively in the cytoplasm (P =.02). Further, although ALK-positive-EBER-1+ cases were LMP-1 negative, ALK-negative-EBER-1+ cases were LMP-1 positive. Our study raises the question whether EBV might have an etiological role in the evolution of ALCLs that lack classical t(2;5).     

The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas

The majority of pediatric anaplastic large cell lymphomas (ALCLs) carry the t(2;5)(p23;q35) chromosomal translocation that juxtaposes the dimerization domain of nucleophosmin with anaplastic lymphoma kinase (ALK). The nucleophosmin-ALK fusion induces constitutive, ligand-independent activation of the ALK tyrosine kinase leading to aberrant activation of cellular signaling pathways. To study the early consequences of ectopic ALK activation, a GyrB-ALK fusion was constructed that allowed regulated dimerization with the addition of coumermycin. Expression of the fusion protein caused a coumermycin-dependent increase in cellular tyrosine phosphorylation and c-Myc immunoreactivity, which was paralleled by a rise in c-myc RNA. To assess the clinical relevance of this observation, c-Myc expression was determined in pediatric ALK-positive and -negative lymphomas. Co-expression of c-Myc and ALK was seen in tumor cells in 15 of 15 (100%) ALK-positive ALCL samples, whereas no expression of either ALK or c-Myc was seen in six of six cases of ALK-negative T-cell lymphoma. C-Myc may be a downstream target of ALK signaling and its expression a defining characteristic of ALK-positive ALCLs.     

Is ALK‐gene rearrangement overlooked in primary gastrointestinal T‐cell lymphomas? About two cases

A 41‐year‐old male patient with a history of ankylosing spondylitis and Crohn disease, treated with immunomodulators and disease‐modifying drugs, was diagnosed with a primary intestinal T‐cell lymphoma that followed a 7.5‐year‐course. This transmural proliferation lacked cytological characteristics of anaplastic large cell lymphoma (ALCL), and was CD8‐positive, and CD30‐ and anaplastic lymphoma kinase (ALK)‐negative by immunohistochemistry (IHC). However, ALK‐gene rearrangement (ALK‐gr) was detected by fluorescence in situ hybridization (FISH) in both initial and persistent disease. The possibility of indolent T‐cell lymphoproliferative disease of the gastrointestinal tract with atypical features (transmural involvement) related to ALK‐gr was suggested. A previous case of aggressive ‘enteropathy‐associated ALCL’ in the context of celiac disease was recently reported, which also lacked anaplastic morphology, and where CD30 and ALK expression was incidentally demonstrated by IHC, and ALK‐gr subsequently confirmed by FISH. These two recent cases represent two distinct rare entities pertaining to the group of primary intestinal T‐cell lymphomas, and they both show unexpected ALK‐gr. This suggests that ALK‐gr has been overlooked in the group of primary intestinal T‐cell lymphomas. Performing IHC and FISH tests for ALK‐gr in primary gastrointestinal T‐cell lymphomas might be of importance, particularly with the advancement of targeted therapy that could impact treatment and prognosis.     

Pathology and genetics of anaplastic large cell lymphoma

Anaplastic large cell lymphomas are a rare subtype of peripheral/mature T-cell lymphomas which are clinically, pathologically and genetically heterogeneous. Both ALK-positive (ALK+) and ALK-negative (ALK-) ALCL are composed of large lymphoid cells with abundant cytoplasm and pleomorphic features with horseshoe-shaped and reniform nuclei. ALK+ ALCL were considered as a definite entity in the 2008 World Health Organization classification of hematopoietic and lymphoid tissues. ALK-ALCL was included as a provisional entity in the WHO 2008 edition and in the most recent 2017 edition, it is now considered a distinct entity that includes cytogenetic subsets that appear to have prognostic implications (e.g. 6p25 rearrangements at IRF4/DUSP22 locus). ALK+ ALCLs are distinct in epidemiology and pathogenetic origin and should be distinguished from ALK-ALCL, cutaneous ALCL and breast implant associated ALCL which have distinct clinical course and pathogenetic features. Breast implant-associated ALCL is now recognized as a new provisional entity distinct from other ALK-ALCL; notably that it is a noninvasive disease associated with excellent outcome. In this article, we will provide an overview of the salient themes relevant to the pathology and genetic mechanisms in ALCL.     

间变性大细胞淋巴瘤形态学及免疫表型观察

目的：探讨间变性大细胞淋巴瘤（ALCL）的形态学和免疫表型特征。方法：对6例ALCL和2例弥温性大B细胞淋巴瘤（DLBCL）进行形态学和免疫组织化学染色（ABC法）观察。结果：6例ALCL中，普通型2例、淋巴组织细胞型2例、ALK－变型2例，均可见单型性或多形性的标志性大细胞。普通型和ALK－变型大细胞沿淋巴窦内生长，而淋巴组织细胞型大细胞则呈散在分布；2例DLBCL形态上颇似ALCL；6例ALCL均为T细胞，CD30＋，儿童患者共同表达ALK＋和EMA＋，年长者则ALK－和EMA－。2例DLBCL均为B细胞，ALK＋、CD30－和EMA－。结论：不论何型ALCL，均可见CD30＋的标志性大细胞，淋巴窦内生长多见于普通型和ALK－变型。ALCK均为T细胞，儿童常有ALK和EMA共同表达，年长者则ALK和EMA－。DLBCL的免疫表型不同于ALCL。     

ALK expression in extranodal anaplastic large cell lymphoma favours systemic disease with (primary) nodal involvement and a good prognosis and occurs before dissemination

AIMS: In anaplastic large cell lymphoma (ALCL), the site of origin has been described as an important prognostic factor. Recently, a fusion protein containing anaplastic lymphoma kinase (ALK) was described in systemic nodal ALCL, and shown to be associated with a good prognosis. The aims of this study were to investigate whether the presence of ALK protein differs between ALCL of different sites of origin; to determine whether ALK expression occurs before dissemination to other sites; and, finally, to investigate whether the site of origin remains a prognostic parameter in ALK negative ALCL. METHODS: ALK expression, as detected by immunohistochemistry using the monoclonal antibodies ALK1 and ALKc, was studied in 85 ALCLs from different sites of origin. In 22 patients, ALK expression was studied in multiple biopsies from different sites (including 13 skin, 16 lymph node, and nine other). Overall survival time was analysed using the Kaplan Meier method. RESULTS: ALK expression was found in 20 of 51 systemic ALCLs with (primary) nodal involvement. No ALK expression was found in 15 primary cutaneous, 14 gastrointestinal, and five nasal ALCLs. Multiple and subsequent biopsies of patients showed ALK expression to be identical to that seen in the primary diagnostic biopsy. Kaplan Meier survival curves showed that in ALK negative ALCLs originating from different sites, primary cutaneous cases are associated with an excellent overall survival, whereas the other cases show a comparable five years survival of less than 40%. CONCLUSIONS: If present, ALK expression favours systemic ALCL with (primary) nodal involvement, and can be used in differentiating between extranodal involvement of systemic (nodal) ALCL and primary extranodal ALCL. ALK is expressed consistently in multiple biopsies of a given patient, indicating that the chromosomal abnormality leading to aberrant ALK expression occurs before dissemination to other sites. Finally, in ALK negative non-cutaneous ALCLs, different sites of origin show comparable poor survival.     

The expression of myeloid antigens CD13 and/or CD33 is a marker of ALK+ anaplastic large cell lymphomas

We retrospectively studied the immunophenotype by flow cytometry of 20 anaplastic large cell lymphomas (ALCLs) (9 anaplastic lymphoma kinase [ALK]+ and 11 ALK-) with a particular emphasis on the aberrant expression of the myeloid associated antigens CD13 and/or CD33. All ALCLs expressed CD45, HLA-DR, and CD30. Most (8/9) ALK+ ALCLs expressed at least 1 surface T-cell antigen (CD4, 6/9 [67%]; CD7, 6/9 [67%]; CD2, 5/9 [56%]; CD5, 2/9 [22%]; CD8, 2/9 [22%]; CD3, 1/9 [11%]). All ALK-ALCLs expressed at least 1 surface T-cell antigen (CD3, 7/11 [64%]; CD4, 6/11 [55%]; CD2, 6/11 [55%]; CD7, 2/11 [18%]; CD5, 1/11 [9%]; CD8, 1/11 [9%]). CD13 and/or CD33 were expressed in all (9/9) ALK+ ALCLs compared with 1 of 11 ALK-ALCLs (9%) (P < .0001). Surface CD3 was more likely expressed in ALK-ALCLs (7/11) compared with ALK+ ALCLs (1/9) (P .03). The myeloid-associated antigens CD13 and/or CD33 are sensitive but not entirely specific markers of ALK+ ALCLs and should not be misinterpreted as indicating myeloid sarcoma.     

Comparison of fascin expression in anaplastic large cell lymphoma and Hodgkin disease

Diagnostic difficulties sometimes arise in distinguishing anaplastic large cell lymphoma (ALCL) from Hodgkin disease (HD), especially the syncytial variant. Study of the biologic features of diagnostic Reed-Sternberg cells in HD, in search of specific markers for Reed-Sternberg cells, has suggested fascin as a relatively specific and sensitive marker. We studied the frequency of fascin expression in 30 ALCLs and 34 cases of classic HD, including 17 cases of the syncytial variant. Staining with CD30 and anaplastic lymphoma kinase (ALK)-1 also was performed in all cases. All ALCL and HD cases showed membranous and Golgi zone CD30 positivity. Fascin stained all HD cases but also stained 67% (20/30) of the ALCLs in a cytoplasmic pattern. Fascin positivity was observed in 59% (10/17) of T-cell ALCLs and 77% (10/13) of null-cell ALCLs; ALK-1-positive ALCLs, regardless of origin, were usually fascin-positive (91% [10/11]). In conclusion, fascin shows strong positivity in all cases of classic HD but also is positive in the majority of ALCLs, including ALK-1-positive and ALK-1-negative cases. Positive staining for fascin is not useful for distinguishing ALCL from HD. In some cases, fascin negativity may help rule out classic HD.     

Clusterin is widely expressed in systemic anaplastic large cell lymphoma but fails to differentiate primary from secondary cutaneous anaplastic large cell lymphoma

A recent study by Wellmann et al (Blood. 2000;96:398-404) detected clusterin expression in all 36 systemic anaplastic large cell lymphomas (ALCLs) tested, but not in any of 9 primary cutaneous ALCLs. Our purpose was to confirm the diagnostic usefulness of clusterin in systemic ALCL and to evaluate its efficacy in distinguishing primary cutaneous ALCL from secondary skin involvement by systemic ALCL. We examined clusterin expression by paraffin immunohistochemical analysis in 41 systemic ALCLs (18 ALK-1+ and 23 ALK-1-), 9 primary cutaneous ALCLs, and 4 secondary cutaneous ALCLs. Clusterin was positive in 95% of systemic ALCLs (39/41), including 100% (18/18) of the ALK-1+ cases and 91% (21/23) of the ALK-1- cases. Five (56%) of 9 primary and 3 (75%) of 4 secondary cutaneous ALCLs were positive for clusterin. Our observations confirm the diagnostic usefulness of clusterin in systemic ALCL, especially in the ALK-1- cases. However, our data fail to demonstrate its value in distinguishing primary from secondary cutaneous ALCL.     

Primary cutaneous CD30 positive T-cell lymphoproliferative disorders with aberrant expression of PAX5: report of three cases

Accurate diagnosis of lymphoma includes the assessment of lineage-specific markers. Hematopoietic and lymphoid tissues express PAX5 exclusively in pro-B-cell to mature B-cell stages. However, some mature PAX5+ T-cell lymphomas have been reported. We report three cases of primary cutaneous CD30+ T-cell lymphoproliferative disorders (LPDs) with PAX5 expression: one cutaneous anaplastic large cell lymphoma (ALCL) and two cases of lymphomatoid papulosis (LyP). The three patients were 26 years old and female, 75 years old and female, and 65 years old and male. In all cases, Hodgkin's and Reed-Sternberg-like large lymphoid cells were present, positive for CD30, fascin, and PAX5, and negative for CD3, CD4, CD8, CD20, CD45RO, CD56, cytotoxic markers, and Epstein-Barr virus. The ALCL was accompanied by lymphadenopathy; the patient died of progressive disease 5 months after diagnosis. The LyP cases were localized in the skin with spontaneous regression. One case was diagnosed during pregnancy, transformed to ALCL, and ended in death 32 months after diagnosis despite multi-agent chemotherapy. This study is the first to address the clinical significance of PAX5+ primary cutaneous CD30+ T-cell LPDs. These cases were distinct regarding PAX5 expression and a relatively aggressive clinical course versus conventional primary cutaneous CD30+ T-cell LPDs.     

Bone marrow involvement in NPM-ALK-positive lymphoma: report of two cases.

Two cases of NPM-ALK-positive anaplastic large cell lymphoma (ALCL) with bone marrow involvement are reported. These cases were recognized within a group of NPM-ALK-positive ALCLs (n = 6) by using immunohistochemistry with the ALK1 monoclonal antibody. In case 1, the bone marrow showed diffuse infiltration of round to spindle-shaped lymphoma cells with moderate fibrosis. In case 2, lymphoma cells intermingling with hematopoietic cells could only be identified by immunohistochemical staining. In contrast to the four NPM-ALK-positive ALCL cases, which showed a cohesive growth pattern in the lymph nodes, the two cases reported here displayed lymphoma cells of smaller size, and they were classified as lymphohistiocytic variants histologically. ALK1 stained small-sized components more clearly than did CD30 (HRS-4). These results suggest that bone marrow involvement of NPM-ALK-positive ALCL may be frequently associated with a histological variant showing a small-sized cell component, and that ALK1 immunostaining is a useful tool to investigate lymphomas for bone marrow involvement.     

The expression of TIA-1+ cytolytic-type granules and other cytolytic lymphocyte-associated markers in CD30+ anaplastic large cell lymphomas (ALCL): correlation with morphology, immunophenotype, ultrastructure, and clinical features

Anaplastic large cell lymphomas (ALCL) are a heterogeneous group of CD30+ large cell lymphomas; the most characteristic type have a T or null cell phenotype, often express epithelial membrane antigen (EMA) and cytolytic lymphocyte markers, and often possess a nonrandom t(2;5)(p23;q35) chromosomal translocation. We studied 22 (19 T, 1 null, 2 B cell) ALCL, including four primary cutaneous ALCL (PC-ALCL), for the expression of TIA-1, the cytotoxic T lymphocyte (CTL) or natural killer (NK) cell-associated antigens CD4, CD8, betaF1, TCRdelta1, CD56, and CD57, the ALCL-associated antigens p80 and EMA, and the Hodgkin's disease-associated marker CD15 to better define the relationship of these markers to histological subtype, primary site, and patient clinical characteristics. TIA-1 expression was seen in 12 of 20 (60%) T or null cell ALCLs with a cytoplasmic, granular distribution. Ultrastructural studies showed cytotoxic-type granules (dense core, multivesicular, and intermediate types) with TIA-1 localized to granules on immunogold labeling. TIA-1 staining strongly correlated with young patient age (< or = 32 years, P < .05) and EMA expression (P < .05). Excluding the four PC-ALCL cases, TIA-1 staining also correlated with p80 expression (P < .05) in all of the T cell cases. Three CD15+ cases were TIA-1-. TIA-1 expression in T or null cell ALCL was seen in all morphological subtypes (2 of 2 small cell variant, 3 of 4 monomorphic variant, and 7 of 14 pleomorphic variant) and primary tumor sites (6 of 14 nodal, 2 of 4 primary cutaneous, 2 of 2 bone, and 2 of 2 soft tissue). TIA-1+ granules were seen in all subsets: 5 of 6 CD4+, 1 of 2 CD8+, 4 of 8 CD56+, and 1 of 2 CD57+ ALCL. Of note, 4 of 10 T or null cell ALCL expressed gammadelta T-cell receptors (TCR), whereas only 1 of 10 T or null cell ALCL was alphabeta TCR+; TCR were not detected in five cases. TIA-1 was expressed by 3 of 4 gammadelta TCR+ ALCL and 1 of 1 alphabeta TCR+ ALCL. These data support a cytotoxic lymphocyte phenotype in most T or null cell ALCL and suggest that some T cell ALCL are derived from cytolytic CD4+ T cells, gammadelta T cells, or NK-like (CD56+ or CD57+) T cells.     

A small cell variant of ALK-positive, CD8-positive anaplastic large cell lymphoma with primary subcutaneous presentation mimicking subcutaneous panniculitis-like T-cell lymphoma

ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is an uncommon non-Hodgkin's lymphoma of T-cell origin, the majority of which express CD4 and show frequent pan-T-cell antigen loss. While most cases of ALK+ ALCL have the common pattern characterized by anaplastic morphology with hallmark cells, a less common but well-recognized variant with a small cell pattern may pose a diagnostic challenge. We report a case of ALK+ ALCL with small cell morphology and CD8 subset restriction in a 53-year-old male patient who presented primarily with multiple recurrent subcutaneous nodules with histopathologic features simulating a subcutaneous panniculitis-like T-cell lymphoma (SPTCL). The case was initially diagnosed as SPTCL but was reconsidered as ALK+ ALCL when the incidental finding of CD30 positivity on a subsequent biopsy prompted an ALK immunostain, which turned out to be positive in the neoplastic T-cells. The diagnosis of ALK+ ALCL, small cell variant, was then confirmed by detection of an ALK gene rearrangement by FISH analysis. This report highlights a case of ALK+ ALCL with a deceiving clinical and histopathologic presentation, and emphasizes the value of immunohistochemical panel studies and genetic tests in such cases to avoid diagnostic errors.     

Frequent expression of the NPM-ALK chimeric fusion protein in anaplastic large-cell lymphoma,lympho-histiocytic type.

The revised European-American lymphoma classification recognizes a subtype of anaplastic large-cell lymphoma (ALCL), termed lympho-histiocytic because of its peculiar cytological composition. As in the case of classical ALCL, this tumor usually occurs in young patients and shows an excellent response to chemotherapy, but some authors have suggested that in reality this is a nonanaplastic T-cell lymphoma rich in histiocytes. In this paper, we show that three of five cases of lympho-histiocytic ALCL stain with anti-ALK antibodies and can therefore be presumed to express the chimeric NPM/ALK protein secondary to (2;5) translocation. These findings further support the inclusion of this as a type of ALCL and not among the nonanaplastic peripheral T-cell lymphomas. Furthermore, they indicate that staining for ALK proteins is a powerful tool for the diagnosis of lympho-histiocytic ALCL, the recognition of which may be difficult on morphological grounds.     

Biochemical detection of novel anaplastic lymphoma kinase proteins in tissue sections of anaplastic large cell lymphoma.

The (2;5) translocation, found in many T-cell and null cell anaplastic large cell lymphomas (ALCLs), creates a hybrid gene encoding the 80-kd NPM-ALK protein. Typically neoplastic cells show labeling of both nucleus and cytoplasm for anaplastic lymphoma kinase (ALK) and for the N-terminus of nucleophosmin (NPM). However, 10-20% of cases exhibit cytoplasmic labeling only for ALK, indicating the probable presence of variants of the classical (2;5) translocation that do not involve the NPM gene. We report the detection (using Western blotting and an in vitro kinase assay) in seven such ALCL cases, of ALK proteins with molecular masses of 85 kd, 97 kd (one case exhibiting a (2;3)(p23;q21) translocation), 104 kd (one case carried a (1;2)(q21;p23) translocation), and 113 kd. Tyrosine kinase activity was detected in four of these proteins, but the N-terminal portion of NPM could not be detected. These results show how ALCL cases that express ALK proteins other than NPM-ALK can be detected by sensitive biochemical techniques using routine cryostat sections.     

Anaplastic Large Cell Lymphoma

Session 8 of the 2005 Society of Hematopathology/European Association for Haematopathology Workshop was devoted to anaplastic large cell lymphoma (ALCL). Most cases submitted were anaplastic lymphoma kinase (ALK)+ ALCL highlighting unusual clinical settings, histologic variants, and variant translocation partners. Cases submitted as ALK- ALCL emphasized the immunohistochemical overlap with classical Hodgkin lymphoma (eg, CD15+/CD30+). It was also clear that consensus histologic and immunohistochemical criteria for the diagnosis of ALK-ALCL are lacking. Many expressed the opinion that ALK-ALCL is not a distinct entity at the immunophenotypic or genetic level and is better designated as peripheral T-cell lymphoma (PTCL), unspecified. Others suggested that the histologic features of ALK-ALCL are distinctive nevertheless and that this diagnosis has meaning that is lost by designating these neoplasms as PTCL, unspecified. This session also included CD30+ anaplastic lymphomas involving skin in which the differential diagnosis included cutaneous ALCL and systemic ALK-ALCL.