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Cutaneous lesions in the setting of myeloproliferative neoplasms and myelodysplastic syndromes are poorly understood. We report 6 patients with pruritic papular eruptions composed of mature T-lymphocytes with large clusters of CD123-positive cells. Double immunohistochemical studies demonstrated a lack of myeloid cell nuclear differentiation antigen in the CD123-positive cells, which expressed SPIB, confirming that they were mature plasmacytoid dendritic cells. Four patients were diagnosed with chronic myelomonocytic leukemia and 2 with myelodysplastic syndromes (AREB-I and myelodysplastic syndromes with 5q deletion, respectively). All patients had a long history of hematological alterations, mainly thrombocytopenia, preceding the cutaneous disorder. Nevertheless, the skin lesions developed in all cases coincidentally with either progression or full-establishment of their hematological disease. Most cutaneous lesions disappeared spontaneously or after corticosteroid treatment. Molecular studies performed in both bone marrow and cutaneous lesions in 2 patients demonstrated the same mutational profile, confirming the specific, neoplastic nature of these mature plasmacytoid dendritic cells-composed cutaneous lesions.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic cutaneous lymphoma. Differential diagnosis with lupus erythematosus panniculitis (LEP) can be challenging and overlapping cases have been described. In this study, we investigate whether gene expression profiling may or not identify markers that can be used to improve our understanding of the disease and to make a precise differential diagnosis. SPTCL, LEP, and overlapping cases were analyzed using a customized NanoString platform including 208 genes related to T-cell differentiation, stromal signatures, oncogenes, and tumor suppressor genes. Gene expression unsupervised analysis of the samples differentiated SPTCL from LEP samples. Most overlapping cases were clustered with LEP cases. Differentially expressed genes were observed when comparing SPTCL with LEP cases; and overlapping with LEP cases. Gene set enrichment analysis recognized gene sets defining each group. In conclusion, SPTCL and LEP have distinctive molecular profiles and the molecular background of overlapping cases more closely resembles LEP.

Acral lymphomatoid papulosis (a-LyP) is a rare clinical variant of LyP whose diagnosis may be challenging. A case series of a-LyP was studied clinically, histopathologically, immunohistochemically and from molecular point of view. Including ours, 25 cases of a-LyP have so far been reported. Clinically, a-LyP may present with exclusive acral involvement, associate mucosal lesions, which is a rare presentation by itself; or may be associated to conventional LyP. The age of presentation was slightly higher than that of conventional LyP (55 vs 45 years) and a male predominance has been observed, as usually reported. Histopathologically, no morphological differences with conventional LyP were observed. LyP type A and E where the main variants. We describe for the first time one case of type D a-LyP. Acral LyP is a rare entity and correct diagnosis can only be reached with clinical and histopathological correlation, so as to avoid aggressive treatment of this indolent lymphoproliferative disorder. This article is protected by copyright. All rights reserved.

[Background] Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited., [Objectives] To evaluate the response and tolerance of BV in a cohort of patients with CTCL., [Methods] We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP)., [Results] Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8 months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3 months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2., [Conclusions] These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases., The Spanish Primary Cutaneous Lymphoma Registry (RELCP) is promoted by the Fundación Piel Sana Academia Española de Dermatología y Venereología, which received an unrestricted grant support from Kyowa Kirin.

Background/Objectives Primary cutaneous lymphomas are rare in pediatric patients. The clinical and histopathological manifestations may differ from those in adults. Due to their low frequency and the insidious clinical picture, the diagnosis is usually delayed. The Spanish Primary Cutaneous Lymphoma Registry was initiated in 2016 as a multicenter registry that would allow better insight into the epidemiological, clinical, histopathological, and treatment response characteristics of patients with primary cutaneous lymphomas. Methods We conducted a prospective observational cohort study of primary cutaneous lymphomas in pediatric patients participating in the Spanish Academy of Dermatology and Venereology (AEDV) Primary Cutaneous Lymphoma Registry. Results At the time of the analysis, 10 patients under 18 years of age out of 799 all-age cases (1.25%) had been included in the registry (7 males, 3 females). The mean age at diagnosis was 9.7 years (SD: 4.8). Seven (70%) had mycosis fungoides, 2 of them had the folliculotropic variant; and 3 (30%) had primary cutaneous marginal zone B-cell lymphoma. Conclusions Primary cutaneous lymphomas are extremely rare in pediatric patients and usually have a good prognosis. Therefore, a high level of suspicion is necessary for the diagnosis. We suggest management by experienced physicians and follow-up into adulthood.

The presence of CD30 cells in cutaneous lymphomas has come to prominence in recent years as a potential diagnostic and therapeutic marker. In primary cutaneous marginal zone B-cell lymphomas, the presence of large CD30 cells with Hodgkin-like features and their significance have not yet been studied. Here we describe the main clinical, histologic, immunophenotypic, and molecular characteristics of 13 cases of primary cutaneous marginal zone lymphomas featuring >10% of CD30 large cells, and analyze their relationship with histologic and clinical progression of the disease and with other morphologic and immunophenotypic features. We report 10 male and 3 female patients, 4 with early-local disease and 8 with locoregional advanced disease without extracutaneous involvement but with a high relapse rate of 69%. We describe an association between a high level of CD30 expression and disease progression, with increased clinical recurrence in cases with >15% of CD30 cells. We also discuss the differential diagnosis with other cutaneous and systemic lymphomas, especially Hodgkin lymphoma.

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, primary cutaneous CD30 lymphoproliferative disorders (pc CD30 LPD) being the second most prevalent. There is evidence that MF and pc CD30 LPD may coexist and share T-cell clonality, suggesting a common origin. These findings were supported by a T-cell receptor clonality assessment by the polymerase chain reaction coupled with capillary electrophoresis, although results produced by this method may be ambiguous. We describe an otherwise healthy 46-year-old man who developed, over the course of 5 months, a tumor consisting of primary cutaneous anaplastic large cell lymphoma and, subsequently, several papules of lymphomatoid papulosis (LyP). Both lymphomas appeared on a single patch of MF, which had been present on the patient's right buttock for at least 2 years. T-cell receptor clonality of the 3 types of neoplastic lesions and apparently non-involved skin were assessed by a next-generation sequencing-based method. We found that MF, primary cutaneous anaplastic large cell lymphoma and LyP harbored the same top 2 clones. Non-involved skin harbored other T-cell clones. In this patient, these findings suggest that MF, LyP and pc CD30 LPD were different clinicopathological manifestations arising from the neoplastic proliferation of the same T-cell clone.

We describe a series of 9 patients with Epstein-Barr virus (EBV)-positive mucocutaneous lymphoproliferative lesions that broadens the concept of EBV-positive mucocutaneous ulcer. We report 5 female and 4 male patients, with an average age of 74 years (range, 55 to 87 y), 2 of whom were HIV-positive. The lesions were located in the oropharynx, skin, and rectal and/or genital mucosa. Histopathologically, 6 cases showed a polymorphic pattern and 3 had a monomorphic and diffuse one, with angiotropism in 4 cases (2 each with the polymorphic and monomorphic patterns). Three of the cases expressed PDL1. In addition to its presence in the neoplastic lymphoid cells, EBV was also detected in adjacent epithelial cells in an oropharyngeal lesion. All cases responded to local therapy or adapted systemic chemotherapy in selected cases. This series extends the spectrum of this disorder to include some HIV-positive cases, patients with multiple lesions confined to a single anatomic area, lesions with an angiocentric pattern, and some cases with monomorphous large-cell cytology. We discuss the differential clinicopathologic diagnosis of this disorder and that of classic EBV large B-cell lymphoma.

Peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS) is a diagnosis of exclusion, showing extreme cytological and phenotypic heterogeneity. Skin involvement of PTCL may be primary or secondary. Diagnosis of histiocytosis may be difficult, requiring clinical-pathological correlation. We describe a laryngeal atypical histiocytic lesion (AHL) and a nasal PTCL, NOS with cutaneous involvement in the same patient presenting with peculiar histopathologic and immunophenotypic features. The laryngeal neoplasm showed morphological and immunophenotypic evidence of histiocytic differentiation and does not fit any other category of the WHO classification nor the revised classification of histiocytosis. The nasal and cutaneous lesions presented features close to natural killer/T-cell lymphoma and gamma-delta T-cell lymphoma but did not meet accurately the WHO criteria. A somatic activating Q61K mutation was found on exon 3 of the NRAS gene in both AHL and PTCL, NOS. The mutation on NRAS gene in both AHL and PTCL, NOS may suggest a common origin from a precursor cell.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft-tissue tumor characterized by a relatively high risk for local recurrence and low risk for metastasis. Many histopathologic variants of DFSP have been described, including the fibrosarcomatous and myoid variants, which may obscure the diagnosis in some cases, especially when arising in unusual locations. Of all the variants described so far, the only one with prognostic relevance is the FS-DFSP variant, which implies tumor progression and a higher possibility for metastasis. The authors report a case of a giant DFSP, located on the vulvar area, which histopathologically showed areas of fibrosarcomatous and myoid differentiation, and discuss the importance of the myoid variant in regards of the debated histogenesis of DFSP.

Follicular malignant melanoma (FMM) is a rare variant of melanoma arising on sun-damaged skin of elderly patients. It is characterized histopathologically by a prominent involvement of 1 or 2 adjacent hair follicles. The authors report 3 new cases of FMM (M:F = 2:1; age range, 23-67 years; median age, 50 years) located on the scalp, cheek, and upper back. Complete effacement of the hair follicle, replaced by neoplastic melanocytes, was observed in 1 case. The interfollicular epidermis and adventitial dermis were involved in all 3 cases. Our series shows that FMM is not restricted to elderly patients but may arise also in young individuals without association with chronic sun damage. FMM should be distinguished from folliculotropic metastases of melanoma and from atypical melanocytic nevi. Although the histopathological features and the term FMM may suggest a derivation from melanocytes of the hair follicle, the exact origin of neoplastic cells is yet unclear, and at least some of these cases may represent folliculotropic examples of primary epidermal malignant melanoma.

Late-onset focal dermal elastosis is a rare disorder of elastic tissue, characterized by a local accumulation of elastic fibers in the mid and deep reticular dermis. This disorder occurs mainly in elderly people and consists of multiple yellow papules that are typically distributed on the sides of the neck and flexural areas, closely resembling pseudoxanthoma elasticum from the clinical point of view. We report 2 sisters who have presented with a 20-year history of multiple yellow papules, mainly located on the dorsum of their hands. They also had few lesions of similar morphology scattered on the anterior aspects of their wrists, thighs, and lower abdomen. Histopathologic study demonstrated a focal increase in thick, interlacing elastic fibers in the mid and deep reticular dermis. The most striking features of our cases were the early age of clinical presentation, the familial involvement, and the predominantly acral distribution of the lesions.

NK/T-cell lymphomas are a group of clonal proliferations of NK- or, rarely, T-cell types and have peculiar clinicopathologic features. Most common site of involvement is the upper aerodigestive tract (nasal cavity, nasopharynx, paranasal sinuses, and palate). Association of autoimmune paraneoplastic disorders with NK/T-cell lymphomas is not well studied. Our patient was diagnosed with NK/T-cell lymphoma stage IV with skin involvement and treated frontline with CHOEP regimen. While he was under treatment, two immune complications presented: anterior uveitis of autoimmune origin refractory to steroids and myositis in lower limbs muscles. Autologous transplantation was rejected due to confirmed early relapse after first-line treatment, and the patient received second-line treatment according to the SMILE scheme, reaching complete response after four cycles. The patient underwent allogeneic transplantation and at the time of manuscript preparation is alive despite multiple complications. The disease should be suspected in patients with rhinitis or recurrent sinusitis, and early biopsy is recommended for all patients to avoid a delay in diagnosis. Our patient also presented symptoms of disease progression after first-line treatment, representing a paraneoplastic process, a very rare phenomenon in T-type lymphomas. This case is novel for the appearance of an inflammatory myositis, a histologically verified paraneoplastic phenomenon that responded to treatment for lymphoma.

We report the unique association of primary cutaneous marginal zone B-cell lymphoma and Rosai-Dorfman disease (RDD)-type histiocytic infiltrates involving the same lesions. The patient was an 82-year-old woman with 3 long-standing, well-circumscribed firm erythematous to brownish plaques on her left arm, right scapular area, and lumbosacral area. Histopathologic examination disclosed a dermal and subcutaneous nodular lymphoplasmacytic infiltrate with evidence of germinal center colonization and light-chain restriction and sheets of S-100 CD68-positive histiocytes with ample pale cytoplasm and occasional emperipolesis of lymphocytes. The neoplastic plasma cells expressed immunoglobulin (Ig) G4. A review of 14 examples of cutaneous RDD showed a substantial number of IgG4-positive cells in only 3 of them, and a review of 8 primary cutaneous marginal zone B-cell lymphomas disclosed only 2 with significant IgG4 expression. The coexistence of lymphomas and RDD has been rarely reported in the literature but only seldom involving the same lymph node and-to the best of our knowledge-never in the skin.

Giant congenital melanocytic nevi (GCMNs) represent a distress to patients for 2 reasons: one is disfigurement, and the other is the increased risk of developing secondary melanocytic tumors, such as benign proliferative nodules (BPNs) and malig- nant melanoma (MM). BPN present as a rapid growth nodule arising within a congenital melanocytic nevus (CMN) that often ulcerates, occurs in children younger than 2 years of age. BPNs arising within a CMN are exceedingly rare after childhood, and very few cases have been described in adults. Despite the worrisome clinical and histologic findings of BPN, most laboratory investigations seem to support their benignity. The distinction between MM and BPN is extremely important, but the histopathology of BPN of GCMN can be a challenge to differentiate from MM. In the recent years, molecular tests that investigate DNA copy number alterations such as fluores- cence in situ hybridization and comparative genomic hybridization have shown promise to help guide the diagnosis of ambiguous melanocytic proliferations arising within CMNs. We report the case of a 22-year-old woman with a nodule arising in a GCMN and with an axillary mass suggesting a nodal metastasis of melanoma, and discuss the unusual clinical, histopathologic, and molecular findings that make this case particularly interesting.

Postirradiation pseudosclerodermatous panniculitis is a rare panniculitic disorder induced by radiotherapy. Clinically, it consists of an indurate plaque localized on the irradiated area that may appear months or even years after radiotherapy was administered. Histopathologically, postirradiation pseudosclerodermatous panniculitis is characterized by a mostly lobular panniculitis without vasculitis, with lipophagic granuloma involving the fat lobules, a variable inflammatory infiltrate of lymphocytes and plasma cells and sclerotic thickening of the connective tissue septa of the subcutis. We report 3 additional cases of this rare variant of panniculitis, in which besides the panniculitis findings, dermal vessels showed sclerotic vessel walls and atypical bizarre fibroblasts with large pleomorphic and hyperchromatic nuclei were interstitially arranged between collagen bundles of the dermis. These dermal findings represent additional histopathologic features supporting the pathogenic role of the radiotherapy in the development of this rare variant of panniculitis.