Primary Cutaneous CD30 Research Articles

Pediatric Case of Primary Cutaneous Eosinophil-Rich CD30+ Anaplastic Large-Cell Lymphoma With Follicular Mucinosis

We report a pediatric case of primary cutaneous CD30 anaplastic large-cell lymphoma showing a combination of rare histopathologic features. The patient was a 14-year-old boy who had a solitary 2 × 1-cm ulcerated nodule with purulent discharge and undermined borders located in the right preauricular area that had been present for 3 weeks. Histopathologically, there was a dense, nonepidermotropic multinodular to diffuse infiltrate involving the reticular dermis and, focally, the subcutis. The infiltrate was composed of numerous eosinophils, neutrophils, small well-differentiated lymphocytes, and large pleomorphic and anaplastic cells. Eosinophils dominated the infiltrate. Focally, the infiltrate was accentuated around hair follicles, many of which manifested features of follicular mucinosis and/or collections of neutrophils in the follicular epithelium. Occasional hair follicles were partly destroyed by the infiltrate. A conspicuous feature was a prominent myxoid change in the stroma surrounding the hair follicles and eccrine glands. Immunohistochemically, the large lymphoid cells expressed CD2, CD3, CD4, and CD30.

Reduced Intensity Allogeneic Stem Cell Transplant for Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic plasmacytoid dendritic cell neoplasm is a rare, aggressive tumor characterized by skin and/or marrow infiltration by CD4+ CD56+ cells. Historically, the tumor was variably thought to arise from either monocytes, T cells or NK cells giving rise to terms such as CD4+/CD56+ acute monoblastic leukemia, primary cutaneous CD4+/CD56+ hematodermic tumor and blastic NK-cell lymphoma. Whilst considerable progress has been made in understanding the histogenesis, the best modality of treatment remains to be defined. We are therefore reporting this case which was successfully treated with a T-deplete allogeneic transplant and the patient is currently alive and in remission 4 years post transplant.

Acquired ichthyosis associated with primary cutaneous CD30+ lymphoproliferative disorders

Acquired ichthyosis (AI) is a group of cornification disorders characterized clinically by dry, rough skin with prominent desquamation, mostly in adulthood. It may be associated with a wide variety of systemic diseases (autoimmune/inflammatory, metabolic, endocrine, infectious), drug reactions or as a paraneoplastic manifestation of several hematologic or solid neoplasms [1]. We report two patients who developed AI in the context of a primary cutaneous CD30+ lymphoproliferative disorder (CD30+ LPD): [...]

Primary Cutaneous CD8+ T-cell Lymphoma Masquerading as Acral Vascular Syndrome

Primary Cutaneous CD8+ T-cell Lymphoma Masquerading as Acral Vascular Syndrome

Neoplastic Cells of Primary Cutaneous CD4+ Small/Medium-sized Pleomorphic T-cell Lymphoma Lack the Expression of Follicular T-helper Cell Defining Chemokine Receptor CXCR5.

Neoplastic Cells of Primary Cutaneous CD4+ Small/Medium-sized Pleomorphic T-cell Lymphoma Lack the Expression of Follicular T-helper Cell Defining Chemokine Receptor CXCR5.

Lymphomatoid Papulosis Type D or an Aggressive Epidermotropic CD8+ Cytotoxic T-cell Lymphoma?

Lymphomatoid papulosis (LyP) is defined as a chronic, recurrent, self-healing eruption of papules and small nodules, characterised by a waxing and waning course, and by histological features of a CD30+ cutaneous T-cell lymphoma CTCL. Classically, 3 histologic subtypes of LyP are recognised: Type A (histiocytic), type B (MFlike) and type C (anaplastic like CTCL) (1). Together with primary cutaneous anaplastic large Tcell lymphoma, LyP is classified as a part of the primary cutaneous CD30+ lymphoproliferative disorders in the WHO-EORTC classification of cutaneous lymphomas (2). Recently, a new histologic LyP variant termed type D, simulating an aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma, but with the typical clinical presentation and indolent course of LyP, has been described (3–5). We describe a new case of this variant, of which diagnosis is particularly challenging and emphasises the importance of cross-disciplinary collaboration.

Angioinvasive Lymphomatoid Papulosis

Lymphomatoid papulosis (LyP) is part of the spectrum of primary cutaneous CD30+ lymphoproliferative disorders. The disease manifests with self-healing papulonodular skin lesions and exhibits a broad range of histological features. Five different histological LyP types, referred to as types A to E, have been delineated. The angioinvasive type E is characterized by angiocentric and angiodestructive tumoral infiltrates of medium sized to large CD30+ atypical lymphocytes with nuclear pleomorphism. In the majority of the cases, the tumor cells express CD8. Because of its histological features and the immunophenotypic findings, this variant of LyP is particularly prone to be misinterpreted as an aggressive lymphoma. This review addresses the clinicopathologic features and differential diagnosis of LyP type E and emphasizes the role of clinicopathologic correlation in the diagnostic workup.

Phase II Trial Of Brentuximab Vedotin For CD30+ Cutaneous T-Cell Lymphomas and Lymphoproliferative Disorders

▪ IntroductionBrentuximab vedotin, an antibody drug conjugate comprising of an anti-CD30 monoclonal antibody (cAC10) attached by a protease-cleavable linker to a microtubule-disrupting agent monomethyl auristatin E (MMAE), was approved for relapsed Hodgkin lymphoma (ORR 75%) and systemic anaplastic large T-cell lymphoma (ALCL; ORR 86%) and the naked cAC10 antibody was shown active in CD30+ skin lymphomas (ORR 70%). Study designTo determine safety and activity of Brentuximab vedotin we completed a Phase II open-label trial of 48 patients with primary cutaneous CD30+ lymphoproliferative disorders including lymphomatoid papulosis (LyP) and primary cutaneous pc-ALCL (pc-ALCL) or CD30+ mycosis fungoides (MF). Eligibility required skin lesion expression of CD30, > 10 Lyp lesions, one or more tumors, and need for systemic therapy. Patients with CD30+ MF were stage IB or higher and had received one or more prior topical or systemic therapies. The antibody conjugate was infused at 1.8 mg/kg every 21 days. Patients achieving a complete response (CR) received two additional doses and those achieving partial responses (PR) after 8 cycles could receive up to 16 doses. Response criteria for LyP were a 50% decrease in lesions, for pc-ALCL were 50 % tumor reduction, and for MF were 50% decrease in modified skin weighted assessment tool mSWAT. CD30 pretreatment skin biopsies and serum sCD30 were correlated with response. ResultsThe 48 evaluable patients who received >2 doses of brentuximab vedotin included 22 females and 26 males with median age of 59.5 years (range 31-86). Their clinical diagnoses are in Table 1: 28 with MF, 2 with pc-ALCL, 9 with only LyP, 7 LyP with MF, and 2 with pc-ALCL/LyP/MF. Overall response rate (ORR) was 71% (34/48) with CR of 35% (17/48). The intent to treat response rate for all 56 patients receiving at least one dose was 61% (34/56). ORR was 50% in 28 MF patients regardless of whether their lesions had low, medium, or high CD30 at baseline. LyP and pc-ALCL patients had a 100% ORR and two pc-ALCL patients had CRs. For LyP, time to response (TTR) was 3 wks (range 3-6) and median duration of response (DOR) of 23 wks (range 6-44). For MF, TTR was 10.5 wks (range 3-39) and DOR was 13.5 wks (range 3-56 wks). Relapse rates in Lyp and pc-ALCL was 40% (8/20) with TTR of 25 wks (range 6-41). In MF responders, 5/14 (36%) relapsed and MTR was 3 wks (range 3-40). Median ORR and disease specific response (DSS) were not reached from date of diagnosis or from first dose. Median progression free survival (PFS) was 9.7 years from diagnosis and 1.68 years from first dose. Soluble CD30 levels from baseline to end of study differed significantly among those patients achieving a CR compared to those with PR or SD (p=.036).The most common related adverse event (AE) of any grade was peripheral neuropathy (PN) in 29/48 (60%): resolved in 14/29 (48%) and ongoing in 15/29 (52%) with 5 grade 2 and 10 grade one. Other AE > 10% were drug rashes (27%), diarrhea (24%), fatigue (30%), alopecia (16%), myalgias (16%), and nausea (14%). Grade 3-4 events included neutropenia (n=5), nausea (n=2), chest pain (n=2), deep vein thrombosis (n=1), transaminitis (n=1) and dehydration (n=1). Dose reductions to 1.2 mg/kg were for grade 2 neuropathy (n=2), transaminitis (n=1) and arthralgia/ fatigue (n=2). There were two deaths from untreated sepsis after one dose. ConclusionThis phase II clinical trial demonstrates that brentuximab vedotin is active for mycosis fungoides (ORR 50%) irrespective of level of CD30+ expression. The ORR was 100% for CD30+ pc-ALCL, and LyP patients and was 71% with a CR of 36% for all evaluable patients.Table 1Response to Brentuximab Vedotin by Clinical DiagnosisPrimary DiagnosisTotal ptsResponse 71% (34/48)Secondary ResponseTime to Response wksDOR (wks)MF2812PR, 2 CR50%10.5 (R 3-39)13.5(R3-56)LyP95 CR, 4 PR100%3 (R 3-6)23 (R 6-44)pc-ALCL22 CR100%3 (R 3)18LyP/MF76 CR, 1 PR100%MF 6 PR 1 SD3 (R 3-9)18 (18- 44)ALCL/LyP22 CR100%LyP PR,PD Disclosures:Duvic:Seattle Genetics: Research Funding. Off Label Use: This is an open label study for Cutaneous T-cell lymphoma and lymphoproliferative disorder. Brentuximab is approved for relapsed and refractory Hodgkins lymphoma. Tetzlaff:Seattle Genetic: Consultancy.

Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report

BackgroundThe etiology of primary cutaneous anaplastic large-cell CD30+ lymphoma is largely unknown, and although an infectious involvement has been suspected, the implication of infectious agents in its pathogenesis is still unclear.FindingsWe report the case of a HIV-negative patient referred to our hospital with a rapidly enlarging skin tumor on her upper eyelid. Surgical excision was performed and histological analysis evidenced a primary cutaneous anaplastic large-cell lymphoma. Due to the ocular localization and to the prominent angiogenic component of the lesion, molecular analyses for the detection of Chlamydophila pneumoniae and HHV8 were performed, revealing the presence of an infection by both pathogens in surgical biopsy and in peripheral blood mononuclear cells.ConclusionsThese findings suggest for the first time a possible association of C. pneumoniae and/or HHV8 infection, or both together, with primary cutaneous anaplastic large-cell lymphoma in non-immunocompromised and HIV-negative subjects. This potential pathogenic association, if confirmed, could provide potential indications for future therapy.

Primary Cutaneous CD4+Small- to Medium-Sized Pleomorphic T-cell Lymphoma

In the recent World Health Organization-European Organisation for Research and Treatment of Cancer classification, primary cutaneous CD4+ small- to medium-sized pleomorphic T-cell lymphoma is listed as a provisional entity that is histopathologically characterized by pleomorphic CD3+/CD4+/CD8-/CD30- T lymphocytes. Clinically, it is characterized by solitary tumors mostly affecting the head and neck area and by an indolent clinical course with an estimated 5-year survival of about 60% to 80%. Currently, therapeutic options include topical or systemic treatment with glucocorticoids, local excision of solitary lesions, radiotherapy, and chemotherapy (e.g., cyclophosphamide) in cases of aggressive clinical behavior or systemic disease. We present the case of a 21-year-old female patient with a 5-year history of a solitary, slowly growing tumor of the right cheek. Histopathologic findings revealed a primary cutaneous CD4+ small- to medium-sized pleomorphic T-cell lymphoma with an admixture of numerous CD20+ B cells representing almost half of the infiltrate. In this patient we achieved a temporary (13 months) complete remission of the lymphoma by oral treatment with doxycycline monohydrate, 200 mg per day. Doxycycline is a relatively nontoxic and well-tolerated oral agent and should be considered as a therapeutic option in primary cutaneous CD4+ small- to medium-sized pleomorphic T-cell lymphoma, especially in cases with a high percentage of B lymphocytes and no signs of systemic disease.

Primary Cutaneous Posttransplant Lymphoproliferative Disorders in Solid Organ Transplant Recipients: A Multicenter European Case Series

Primary cutaneous posttransplant lymphoproliferative disorders (PTLD) are rare. This retrospective, multicenter study of 35 cases aimed to better describe this entity. Cases were (re)-classified according to the WHO-EORTC or the WHO 2008 classifications of lymphomas. Median interval between first transplantation and diagnosis was 85 months. Fifty-seven percent of patients had a kidney transplant. Twenty-four cases (68.6%) were classified as primary cutaneous T cell lymphoma (CTCL) and 11 (31.4%) as primary cutaneous B cell PTLD. Mycosis fungoides (MF) was the most common (50%) CTCL subtype. Ten (90.9%) cutaneous B cell PTLD cases were classified as EBV-associated B cell lymphoproliferations (including one plasmablastic lymphoma and one lymphomatoid granulomatosis) and one as diffuse large B cell lymphoma, other, that was EBV-negative. Sixteen (45.7%) patients died after a median follow-up of 19.5 months (11 [68.8%] with CTCL [6 of whom had CD30+ lymphoproliferative disorders (LPD)] and 5 [31.2%] with cutaneous B cell PTLD. Median survival times for all patients, CTCL and cutaneous B cell PTLD subgroups were 93, 93, and 112 months, respectively. Survival rates for MF were higher than those for CD30+ LPD. The spectrum of primary CTCL in organ transplant recipients (OTR) is similar to that in the general population. The prognosis of posttransplant primary cutaneous CD30+ LPD is worse than posttransplant MF and than its counterpart in the immunocompetent population. EBV-associated cutaneous B cell LPD predominates in OTR.

Primary Cutaneous CD4+ Small to Medium‐Size Pleomorphic T‐Cell Lymphoma in a 12‐Year‐Old Girl

Primary cutaneous CD4+ small to medium-size pleomorphic T-cell lymphoma (PCSM-TCL) is a rare disease that has been added as a provisional entity to the World Health Organization European Organization for Research and Treatment of Cancer (WHO-EORTC) classification of lymphomas with primary cutaneous manifestations. Patients commonly present with a solitary nodule or plaque on the head or upper trunk, but are usually otherwise in good health. The prognosis is favorable, but the optimal treatment has not been defined. Recent publications have described the expression of programmed death-1 in PCSM-TCL and T-cell pseudolymphoma, suggesting a diagnostic value of this marker in the differential diagnosis of PCSM-TCL in contrast to other types of cutaneous T-cell lymphoma. We present the case of a 12-year-old girl with a tumor of the right supraorbital area. She was treated as an outpatient four times with intralesional triamcinolone acetonide at intervals of 3 to 4 weeks. In addition to the case history, this report includes the clinical and histologic findings and a review of the current literature.

Primary cutaneous CD4 positive small/medium T-cell lymphoma with high proliferation index and CD30-positive large lymphoid cells

Primary cutaneous CD4 positive small/medium pleomorphic T-cell lymphoma (SMPTCL) represents a provisional subtype of primary cutaneous T-cell lymphoma with indolent clinical course. A few aggressive fatal cases with increased proliferation rate and few infiltrating CD8 positive T-cells have been reported. We describe a case of SMPTCL with an increased proliferation rate, admixed CD30-positive large lymphoid cells, and few infiltrating CD8 positive T-cells. The lymphoma cells were positive for CD3, CD4, CD2 and CD5, and negative for CD8. A subset of the lymphoma cells was positive for follicular helper T-cell markers bcl-6 and PD-1. There were approximately 20% CD30-positive large lymphoid cells, and Ki-67 showed a moderately high proliferation rate (~40%), mostly in the large lymphoid cells. CD8 infiltrating T-cells were few (<5%). The patient had an indolent disease with complete response to radiation therapy. To the best of our knowledge, this is the first reported case of SMPTCL with an increased proliferation rate and large CD30+ cells that followed an indolent clinical course.

Investigation of molluscum contagiosum virus, orf and other parapoxviruses in lymphomatoid papulosis

Lymphomatoid papulosis (LyP) is a primary cutaneous CD30+ lymphoproliferative disorder with large, atypical CD-30+ cells, which despite their ominous appearance, also occur in reactive processes, such as CD30+ cutaneous lymphoid hyperplasia. As most causes of CD30+ cutaneous lymphoid hyperplasia are viral,1 we explored the possibility that poxvirus or parapoxvirus could be detected in lesions of LyP. Following University of Iowa Institutional Review Board approval, nine patients with a diagnosis of LyP that had available skin tissue blocks were included. For negative controls, two scar tissue samples were included. DNA was extracted from formalin-fixed, paraffin-embedded slides. Tissue was dewaxed by addition of xylene, vortexing, and centrifuging; xylene was removed and the pellet was rehydrated in 100% ethanol. After vortexing, centrifugation, and air drying, the sample was resuspended in digestion buffer and was incubated at 55°C for 4–6 hrs. Chelex-100 (BioRad) was added to a final concentration of 5%. The mixture was boiled 8 min, chilled 2 min, and centrifuged for 5 min at 4°C. The supernatant was transferred to a fresh centrifuge tube as template. Quantitative real-time polymerase chain reaction (q-PCR) was performed to detect Molluscum contagiosum virus p43K gene2; 10 ul of DNA was used in each assay. To ensure sufficient DNA was present and amplification was not due to presence of an inhibitor, the single copy RNaseP gene was detected by amplification of the DNA sample using a TaqMan RNaseP detection reagent kit (Applied Biosystems). A plasmid containing MCV p43K gene served as a positive control2. Parapoxvirus generic and orf virus specific q-PCR assays were also performed on the extracted DNA3, with positive controls using nucleic acid from Ovine Ecthyma Vaccine (Colorado Serum Company) and orf virus. No molluscum contagiosum, parapoxvirus generic, or orf virus DNA was detected the LyP samples or scars. Of the many infectious conditions associated with CD30+ cutaneous lymphoid hyperplasias, the most commonly associated viruses have been parapoxviruses (28.5%), herpes simplex and varicella zoster viruses (25%), and molluscum contagiosum virus (10.7%)1. Extrapolating these findings to true CD30+ lymphoproliferative disorders, previous studies have explored the possibility that LyP may represent a virally-induced cutaneous lymphoid hyperplasia. One analysis of LyP specimens by PCR demonstrated one out of nine LyP samples with detectable HHV 6 DNA, but no detectable HSV 1 and 2 or EBV DNA. 4. Recently, biopsy specimens of cutaneous lymphomas (including 3 cases of LyP) were assayed for Merkel cell polyoma virus, human polyomavirus type 6, human polyoma virus type 7, and trichodysplasia spinulosa-associated polyoma virus DNA by q- PCR; the cases of LyP were negative for all viral types5. As LyP and parapoxvirus and poxvirus virally-mediated CD30+ cutaneous lymphoid hyperplasias share overlapping clinical features (papular lesions, generally indolent course) and pathologic features (large, atypical CD30+ lymphoid infiltrates), LyP appears an intriguing candidate for induction by viral infection. However, the lack of detection of viral DNA in our LyP specimens argues against a link between parapoxviruses or molluscum contagiosum virus and LyP, although the role of sampling and stage of lesions should be considered.

Characteristics of primary cutaneous lymphoma according to WHO-EORTC classification in Korea

Primary cutaneous lymphoma (PCL) is an extranodal non-Hodgkin lymphoma with primary involvement of the skin. Epidemiological data on PCLs according to the World Health Organization/European Organization for Research and Treatment of Cancer classification (WHO-EORTC) has not been investigated in Korea to date. To evaluate the demographic characteristics, clinical and histological features, and survival data of patients with PCL according to the WHO-EORTC classification. In total, 93 patients with PCL were retrospectively identified from an extensive review of medical records over a 16-year period. The tumours found included primary cutaneous CD30+ lymphoproliferative disorders, extranodal natural killer/T-cell lymphoma and primary cutaneous diffuse large B-cell lymphoma. We found that 81.6% of the patients had primary cutaneous T-cell and natural killer-cell lymphoma, and 16.2% had primary cutaneous B-cell lymphoma, with 2.2% having precursor haematological neoplasms. The median age was 52 years (range 3-95) and the male : female ratio was 1: 1.16. The 5-year survival rate was 92.5%. The incidence rates of many PCL subtypes in Koreans differ from those of other countries.

Mycosis Fungoides

Session 1 of the 2011 Workshop of the Society for Hematopathology and European Association for Haematopathology focused on mycosis fungoides (MF), the most common cutaneous lymphoma. The 62 cases in this case group demonstrated a wide spectrum of clinicopathologic features, including those seen in typical cases as well as those, by contrast, with atypical clinical history, morphology, immunophenotype, and/or genotype. Of the 62 cases, 27 (44%) were presented at the workshop and highlighted diagnostic challenges plus related issues. This report summarizes the approach recommended for making a confident diagnosis of MF and its clinically significant variants; emphasizes pitfalls in evaluating early MF, assessing nodal involvement, and diagnosing transformed MF; and discusses the relationship between MF and primary cutaneous CD30+ T-cell lymphoproliferative disorders. Last, Sézary syndrome is discussed, with concentration on those features distinct from MF.

Non–Mycosis Fungoides Cutaneous T-Cell Lymphomas

Primary cutaneous T-cell lymphomas (CTCL) excluding mycosis fungoides (MF) were discussed in 2 sessions of the 2011 Society for Hematopathology/ European Association of Haematopathology Workshop, Los Angeles, CA. Session 2 focused on primary cutaneous CD30+ T-cell lymphoproliferative disorders and their differential diagnosis, including systemic CD30+ T-cell lymphoma secondarily infiltrating the skin. Interesting features like special morphologic variants and atypical phenotypes were presented. In addition, the possibility of rare ALK+ primary cutaneous lymphomas was discussed. Session 3 examined other more uncommon non-MF CTCLs, including subcutaneous panniculitis-like T-cell lymphoma, extranodal NK/T-cell lymphoma, hydroa vacciniforme-like T-cell lymphoma, and rare subtypes of primary cutaneous peripheral T-cell lymphoma, not otherwise specified. In addition, systemic T-cell lymphomas involving the skin secondarily, such as angioimmunoblastic T-cell lymphoma, were included in this session. In this report, novel findings, areas of special interest, and diagnostic challenges emerging from the cases submitted to the workshop will be highlighted. The necessity to integrate histologic, immunophenotypical, genetic, and in particular, clinical data to arrive at the correct diagnosis, and subsequently provide adequate treatment, is emphasized.

Primary Cutaneous CD8+ Small- to Medium-Sized Lymphoproliferative Disorder in Extrafacial Sites

Three cases with CD8+ small- to medium-sized lymphoproliferations in the skin at extrafacial sites are described. Clinically, the patients presented with papulonodular or plaque-like lesions without preceding patches. Histopathologically, nonepidermotropic nodular or diffuse infiltrates were composed of small- to medium-sized pleomorphic lymphocytes, which expressed CD8 (more than 80% of the cells) and granzyme B (60%-70% of the cells), but were negative for CD4, CD30, and CD56. There was no association with Epstein-Barr virus. A clonal T-cell population was detected in 2 patients. Staging examinations did not reveal extracutaneous involvement. The 2 patients with solitary lesions underwent complete remission after radiation therapy, whereas 1 patient developed multifocal lesions and several recurrences. These CD8+ small- to medium-sized lymphoproliferations of the skin at extrafacial sites may belong to a spectrum of phenotypically and prognostically heterogeneous cutaneous small- to medium-sized lymphoid proliferations, which are characterized by an indolent course in most patients.

Dermatopathology Update

This past year has seen a wealth of new developments in dermatopathology that appear to herald the dawning of a new era. Advances in molecular biology and the simplification of techniques have put molecular tests within reach of routine clinical practice and led to a radical change in our approach to lesions such as melanoma; in the future, the genetic characterization of these lesions will be an essential requirement for establishing diagnosis, prognosis, and therapy. Technological innovations have also reached dermatology departments: the introduction of ultrasound scans has propitiated the use of fine-needle aspiration cytology, which allows samples to be stained and studied immediately, thereby facilitating diagnosis of superficial and lymph-node lesions, and allowing staging of tumors such as melanoma. Targeted cancer therapies have led to the introduction of more sensitive and specific systems for identifying new targets, have reawakened interest in forgotten diseases such as aggressive basal cell carcinoma, and have led to dermatological reactions that, together with those caused by biologic drugs, we are just beginning to recognize. Consolidated techniques such as immunohistochemistry continue to advance with the addition of new antibodies that contribute considerably to improved diagnosis. New clinicopathologic diseases have also been described or characterized this year, including 2 new types of melanoma, and progress has been made in our knowledge of other diseases, such as primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma. These topics, together with new developments in adnexal tumors, alopecia, and other lesions, will be discussed in this review.

TCR-γ Expression in Primary Cutaneous T-cell Lymphomas

Primary cutaneous γδ T-cell lymphomas (PCGD-TCLs) are considered a subgroup of aggressive cytotoxic T-cell lymphomas (CTCLs). We have taken advantage of a new, commercially available antibody that recognizes the T-cell receptor-γ (TCR-γ) subunit of the TCR in paraffin-embedded tissue. We have analyzed a series of 146 primary cutaneous T-cell lymphomas received for consultation or a second opinion in the CNIO Pathology Department. Cases were classified according to the World Health Organization 2008 classification as mycosis fungoides (MF; n=96), PCGD-TCLs (n=5), pagetoid reticulosis (n=6), CD30(+) primary cutaneous anaplastic large cell lymphomas (n=5), primary cutaneous CD8 aggressive epidermotropic CTCLs (n=3), primary cutaneous CTCL, not otherwise specified (n=4), and extranodal nasal-type NK/T-cell lymphomas primarily affecting the skin or subcutaneous tissue (n=11). Sixteen cases of the newly named lymphomatoid papulosis type D (LyP-D; n=16) were also included. In those cases positive for TCR-γ, a further panel of 13 antibodies was used for analysis, including TIA-1, granzyme B, and perforin. Clinical and follow-up data were recorded in all cases. Twelve cases (8.2%) were positive for TCR-γ, including 5 PCGD-TCLs, 2 MFs, and 5 LyP-Ds. All 5 PCGD-TCL patients and 1 MF patient died of the disease, whereas the other MF patient and all those with LyP-D were alive. All cases expressed cytotoxic markers, were frequently CD3(+)/CD8(+), and tended to lose CD5 and CD7 expressions. Eight of 12 and 5 of 11 cases were CD30(+) and CD56(+), respectively. Interestingly, 5/12 TCR-γ-positive cases also expressed TCR-BF1. All cases analyzed were negative for Epstein-Barr virus-encoded RNA. In conclusion, TCR-γ expression seems to be rare and is confined to cytotoxic primary cutaneous TCLs. Nevertheless, its expression is not exclusive to PCGD-TCLs, as TCR-γ protein can be found in other CTCLs. Moreover, its expression does not seem to be associated with bad prognosis by itself, as it can be found in cases with good and bad outcomes.