Primary Cutaneous CD30-positive T-cell Research Articles

DUSP22-rearranged primary cutaneous CD30-positive T-cell lymphoproliferative disorders and adult T-cell leukemia/lymphoma frequently share the LEF1+/TIA1− immunophenotype

DUSP22 rearrangements are genetic alterations observed in a subset of systemic anaplastic large cell lymphoma (S-ALCL), primary cutaneous anaplastic large cell lymphoma (C-ALCL), and lymphomatoid papulosis (LyP). Previous investigations have shown that the LEF1+/TIA1− immunoprofile and MSC E116K mutations are highly associated with DUSP22 rearrangement in ALCL. However, the existing literature primarily focuses on S-ALCL. Our understanding of the LEF1/TIA1 immunoprofile and MSC mutation status in C-ALCL/LyP is still limited. In this study, we aimed to assess LEF1/TIA1 expression and MSC mutations in a cohort of 23 C-ALCL/LyP cases, along with a control group of histological mimickers. DUSP22 rearrangements were detected by fluorescence in situ hybridization in eight cases (6/10 C-ALCL, 2/13 LyP). We found LEF1 expression in five out of eight (63%) DUSP22-rearranged cases (3/6 C-ALCL, 2/2 LyP), and none of the 15 cases lacking DUSP22 rearrangements. Furthermore, we also found frequent LEF1 expression in adult T-cell leukemia/lymphoma (ATLL; 10 of 11, 91%) within the control group. TIA1 expression was consistently negative in all DUSP22-rearranged C-ALCL/LyP and ATLL cases tested. MCS E116K mutation was identified in one of five DUSP22-rearranged C-ALCL cases. RNA sequencing of a DUSP22-rearranged C-ALCL revealed a novel DUSP22::SNHG fusion coexisting with a CD58::WNT2B fusion. In conclusion, our findings demonstrated a lower rate of LEF1 expression in DUSP22-rearranged C-ALCL/LyP compared to previous reports that predominantly focused on S-ALCL. Moreover, we observed that the majority of ATLL cases also expressed LEF1, suggesting that the LEF1+/TIA1− immunoprofile does not differentiate DUSP22-rearranged C-ALCL/LyP from ATLL.

Prevalence of T-cell antigen losses in mycosis fungoides and CD30-positive cutaneous T-cell lymphoproliferations in a series of 153 patients

Mycosis fungoides (MF) and primary cutaneous CD30-positive T-cell lymphoproliferative disorders (CD30LPD) are the most frequent primary cutaneous T-cell lymphomas. Our objective was to study pan-T-cell antigens and PD-1 expression in a large cohort of MF and CD30LPD with a special interest in antigen losses as a diagnostic tool. We retrospectively reviewed 160 consecutive samples from 153 patients over a 3 year period, including 104 with MF and 49 with CD30LPD. As controls, benign inflammatory dermatoses (BID, n=19) were studied. A semi-quantitative evaluation of CD2, CD3, CD4, CD5, CD7, CD8 expression was performed. PD-1 and double stainings (CD3+CD7 and PD-1+CD7) were performed in a subset of MF cases. CD8+ MF was frequent (23%) and CD7 was the most frequently lost antigen in both MF (45%) and CD30LPD (86%), while no significant T-cell antigen loss was observed in BID. CD7 loss was less frequent in folliculotropic MF (p<0.001). PD-1 was variably expressed in MF with no differences with BID. The CD3+/CD7- and PD-1+/CD7- neoplastic lymphocytes were highlighted by the use of chromogenic double staining experiments in MF with a CD7 loss identified with single staining. Multiple pan T-cell antigen losses were mostly seen in CD30LPD with CD2 being the most frequently preserved marker (90%). While PD-1 does not discriminate between MF and BID, CD7 is frequently lost in MF infiltrates as well as other pan-T-cell antigens in CD30LPD, which can be used as routine markers for diagnosis. We recommend the use of CD7 in addition to CD3, CD4 and CD8 as a minimal immunohistochemical panel for MF assessment, and the use of double stainings for CD3 and CD7 in difficult cases.

CD30-positive primary cutaneous lymphoproliferative disorders: molecular alterations and targeted therapies.

Primary cutaneous CD30-positive T-cell lymphoproliferative disorders are the second most common subgroup of cutaneous T-cell lymphomas. They include two clinically different entities with some overlapping features and borderline cases: lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. Molecular studies of primary cutaneous anaplastic large cell lymphoma reveal an increasing level of heterogeneity that is associated with histological and immunophenotypic features of the cases and their response to specific therapies. Here, we review the most significant genetic, epigenetic and molecular alterations described to date in primary cutaneous CD30-positive T-cell lymphoproliferative disorders, and their potential as therapeutic targets.

Primary cutaneous extranodal natural killer/T-cell lymphoma misdiagnosed as peripheral T-cell lymphoma: the importance of EBV in situ hybridization for diagnosis

Cutaneous non-mycosis fungoides (MF) T- and NK/T-cell lymphomas are heterogeneous with different degrees of aggressiveness. Extranodal natural killer/T-cell lymphoma (ENKTL) is a predominantly extranodal lymphoma associated with EBV. In our recent Asian collaborative study on primary cutaneous ENKTL, we identified five patients initially misdiagnosed as various types of PTCL because EBER was not performed. Three patients were males and two were females, with a median age of 45 years (range 28~71 years). Based on the initial diagnoses (two as PTCL, two as primary cutaneous CD30-positive T-cell lymphoproliferative disorders and one as subcutaneous panniculitis-like T-cell lymphoma), all patients received CHOP chemotherapy and three with additional radiotherapy. All patients experienced persistent disease or relapse despite treatment (mean duration 11 months, range 1~24 months). These rare tumors often pose significant diagnostic challenges to the practicing dermatopathologists and (hemato)pathologists. We proposed to include EBER as a screening assay for primary cutaneous non-MF T-cell lymphoma, at least in East Asia where the relative frequency of such tumors is higher than in the West. As novel chemotherapy regimen SMILE (L-asparaginase, methotrexate, ifosphamide, etoposide, and dexamethasone) has been shown to be more effective than CHOP for ENKTL, a correct diagnosis of ENKTL is very important.

Primary cutaneous CD30-positive T-cell lymphoproliferative disorders with biallelic rearrangements of the DUSP22-IRF4 locus on 6p25.3: Report of 3 cases

Primary cutaneous CD30-positive T-cell lymphoproliferative disorders with biallelic rearrangements of the DUSP22-IRF4 locus on 6p25.3: Report of 3 cases

ALK-positive anaplastic large cell lymphoma limited to the skin: clinical, histopathological and molecular analysis of 6 pediatric cases. A report from the ALCL99 study

Anaplastic large cell lymphomas are peripheral T-cell lymphomas that are characterized by a proliferation of large anaplastic blasts expressing CD30. In children, systemic anaplastic large cell lymphomas often present at advanced clinical stage and harbor translocations involving the anaplastic lymphoma kinase (ALK) gene leading to the expression of chimeric anaplastic lymphoma kinase (ALK)-fusion proteins. Primary cutaneous anaplastic large cell lymphoma is regarded as an ALK-negative variant confined to the skin and is part of the spectrum of primary cutaneous CD30-positive T-cell lymphoproliferative disorders. Thirty-three of 487 pediatric patients registered within the Anaplastic Large Cell Lymphoma-99 trial (1999 to 2006) presented with a skin limited CD30-positive lympho-proliferative disorder. In 23 of the 33 patients, material for international histopathological review was available, and the cases were studied for histopathological, immunophenotypical and clinical features as well as for breaks within the ALK gene. Five of 23 cases and one additional case (identified after closure of the trial) expressed ALK-protein. Complete staging excluded any other organ involvement in all children. Expression of ALK proteins was demonstrated by immunohistochemistry in all cases and the presence of breaks of the ALK gene was genetically confirmed in 5 evaluable cases. The histopathological and clinical picture of these skin-restricted ALK-positive lymphomas was indistinguishable from that of cutaneous anaplastic large cell lymphoma. Five children presented with a single skin lesion that was completely resected in 4 and incompletely resected in one. Three of these patients received no further therapy, 2 additional local radiotherapy, and one chemotherapy. All children remain in complete remission with a median follow up of seven years (range 1-8 years). We present 6 pediatric cases of ALK-positive primary cutaneous anaplastic large cell lymphomas. After thorough exclusion of systemic involvement, therapy confined to local measures seems to be sufficient to induce cure.

Primary cutaneous CD30-positive T-cell lymphoproliferative disorders

Primary cutaneous CD30-positive T-cell lymphoproliferative disorders

Lymphohistiocytic anaplastic large cell lymphoma involving skin: A diagnostic challenge

Systemic anaplastic large cell lymphoma (ALCL) involving the skin should be differentiated from primary cutaneous CD30-positive T-cell lymphoproliferative disorders. The lymphohistiocytic variant of ALCL (LH-ALCL) is rich in reactive histiocytes with relatively few neoplastic cells, which pose a diagnostic challenge. We present a case of LH-ALCL involving skin mimicking granulomatous inflammation. A 30-year-old woman presented with cervical lymphadenopathy and multiple non-tender, non-itching, erythematous papules over the neck, chest, and abdomen. Biopsy of the cervical lymph node showed LH-ALCL with null cell phenotype. Microscopically, the cutaneous lesion was located predominately around the hair follicle, with numerous reactive histiocytes and scanty medium-sized lymphoma cells expressing CD30 and anaplastic lymphoma kinase (ALK) protein. Furthermore, an ALK gene rearrangement was demonstrated by locus-specific interphase fluorescent in situ hybridization, confirming cutaneous involvement with LH-ALCL. LH-ALCL involving the skin is a rare event, and the numerous reactive histiocytes may mask scanty tumor cells. In addition to B-and T-cell markers, (dermato) pathologists must be aware of this entity in cutaneous lymphohistiocytic proliferations and perform immunostaining for CD30 and ALK to reach a correct diagnosis.

Primary Cutaneous CD30-Positive T-cell Lymphoma of the Eyelids

A case of a cutaneous CD30-positive pleomorphic T-cell lymphoma primarily involving both the upper and lower left eyelids of a 50-year-old man is reported. A firm, partly ulcerated mass was the initial and only clinical sign. Histopathologic examination of a shave biopsy revealed atypical neoplastic cells in close relation with epidermal appendages, suggesting epithelial derivation of the lesion. Nevertheless, the results of the immunohistochemical testing disclosed diffuse reactivity for T-cells and CD30 positivity in more than 70% of neoplastic cells, thus supporting the diagnosis of a CD30-positive lymphoma, T-cell phenotype. The diagnosis of this entity is particularly challenging, especially at such a site, since primary ocular adnexal non-Hodgkin lymphomas are virtually of B-cell type. The differential diagnosis and a review of the relevant literature are presented.

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Primary cutaneous CD30 positive T-cell lymphoproliferative disorders are divided into anaplastic large cell lymphoma, borderline disorder, and lymphomatoid papulosis (LyP) by the rate of CD30 positive cells among the infiltrate. Furthermore, in LyP, B cell infiltration is sometimes observed and self-healing is clinically observed. On the other hand, self-healing is seldom observed in lymphocytoma cutis. Histologically, secondary lymphoid follicles are constantly observed in lymphocytoma cutis, but not in LyP.In this case, self-healing of the solitary nodule was clinically observed, and a few primary lymphoid follicles and 10% of CD30 positive cells were respectively observed at the deep dermis or subcutaneous layer and among the T-cell dominant area in the dermis on histology and immunohistology. So this case was considered to be LyP rather than lymphocytoma cutis. [Skin Cancer (Japan) 2004; 19: 173-177]

Expression of CD44 and CD44v6 in primary cutaneous CD30 positive T-cell lymphoproliferative disorders.

Expression of the lymphocyte homing receptor CD44 and its variant form, CD44v6, have been linked to unfavorable prognosis and tumor dissemination in non-Hodgkin's lymphoma. The role of CD44 and CD44v6 in primary cutaneous lymphomas may not necessarily correlate with that observed in nodal lymphomas. Our study attempts to evaluate the expression pattern of CD44 and CD44v6 in primary cutaneous CD30 positive T-cell lymphoproliferative disorders including primary cutaneous anaplastic large cell lymphoma (cALCL) and lymphomatoid papulosis (LyP) and compared the expression between these two subgroups. Immunohistochemical staining of CD44 and CD44v6 was performed on 10 cALCL and 18 LyP cases. CD44 consistently expressed in all cases of primary cutaneous CD30 positive T-cell lymphoproliferative disorders. In contrast with previous studies, our results showed that CD44v6 expressed in 46% of all cases, including 50% cALCL and 44% LyP. There was no statistic difference in expression of CD44 or CD44v6 between cALCL and LyP subgroups. These results provide a new evidence that CD44v6 is expressed in a subset cases of primary cutaneous CD30 positive T-cell lymphoproliferative disorders and suggest that other factors or molecules rather than CD44 or CD44v6 are responsible for the difference between cALCL and LyP.

Lymphomatoid papulosis and human herpesviruses--A PCR-based evaluation for the presence of human herpesvirus 6, 7 and 8 related herpesviruses.

Lymphomatoid papulosis (LyP) is a chronic, recurrent lymphoproliferative disorder of the skin that belongs to the group of primary cutaneous CD30-positive T-cell lymphomas. Ultrastructural and clinical features of LyP suggest that it has a viral etiology. Human herpesviruses have been proposed as causative cofactors for LyP because of their oncogenic potential and their association with other lymphomas. LyP skin lesions and a LyP-derived cell line were examined for the presence of the recently discovered oncogenic human herpesvirus 8 (HHV-8) and the two T-lymphotropic human herpesviruses 6 and 7 (HHV-6 and HHV-7) by nested polymerase chain reaction (PCR) using virus-specific oligonucleotide primers. Furthermore, a recently described method involving degenerate PCR primers was applied to detect highly conserved DNA sequences shared by a variety of herpesviruses, especially oncogenic gamma-herpesviruses, in an attempt to identify a yet undiscovered herpesvirus associated with LyP. HHV-6 and 8 could not be found in 26 archival and 11 snap-frozen LyP lesions and a LyP tumor cell line. HHV-7 DNA sequences were detected in 14% (5 of 37) of LyP samples. HHV-6 was found in 23% (3 of 13) and HHV-7 in 8% (1 of 13) of normal skin samples from healthy individuals, respectively. Using degenerate PCR primers to amplify the highly conserved polymerase region of herpesviruses, no DNA sequences related to human herpesviruses could be detected. LyP is not associated with HHV-6, HHV-7 and HHV-8. In addition, the studies using degenerate PCR primers do not indicate the presence of a previously undescribed human herpesvirus in LyP.