Neoadjuvant relatlimab and nivolumab in resectable melanoma.

Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma1. We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate2. The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid Tumors 1.1 was 57%. No grade 3-4 immune-related adverse events were observed in the neoadjuvant setting. The 1- and 2-year recurrence-free survival rate was 100% and 92% for patients with any pathologic response, compared to 88% and 55% for patients who did not have a pathologic response (P = 0.005). Increased immune cell infiltration at baseline, and decrease in M2 macrophages during treatment, were associated with pathologic response. Our results indicate that neoadjuvant relatlimab and nivolumab induces a high pCR rate. Safety during neoadjuvant therapy is favourable compared to other combination immunotherapy regimens. These data, in combination with the results of the RELATIVITY-047 trial1, provide further confirmation of the efficacy and safety of this new immunotherapy regimen.

Nuclear Localization of Yes-Associated Protein Is Associated With Tumor Progression in Cutaneous Melanoma.

Yes-associated protein (YAP), an effector molecule of the Hippo signaling pathway, is expressed at high levels in cutaneous melanoma. However, the role of YAP in melanoma progression according to cellular localization is poorly understood. Tissues from 140 patients with invasive melanoma were evaluated by immunohistochemistry. Flow cytometry, western blotting, viability assays, wound healing assays, verteporfin treatment, and xenograft assays were conducted using melanoma cell lines B16F1 and B16F10 subjected to YapS127A transfection and siYap knockdown. Nuclear YAP localization was identified in 63 tumors (45.0%) and was more frequent than cytoplasmic YAP in acral lentiginous and nodular subtypes (P = .007). Compared with cytoplasmic YAP melanomas, melanomas with nuclear YAP had higher mitotic activity (P = .016), deeper invasion (P < .001), and more frequently metastasized to lymph nodes (P < .001) and distant organs (P < .001). Patients with nuclear YAP melanomas had poorer disease-free survival (P < .001) and overall survival (P < .001). Nuclear YAP was an independent risk factor for distant metastasis (hazard ratio: 3.206; 95% CI, 1.032-9.961; P = .044). Proliferative ability was decreased in siYapB16F1 (P < .001) and siYapB16F10 (P = .001) cells and increased in YapS127AB16F1 (P = .003) and YapS127AB16F10 (P = .002) cells. Cell cycle analysis demonstrated relative G1 retention in siYapB16F1 (P < .001) and siYapB16F10 (P < .001) cells and S retention in YapS127AB16F1 cells (P = .008). Wound healing assays showed that Yap knockdown inhibited cell invasion (siYapB16F1, P = .001; siYapB16F10, P < .001), whereas nuclear YAP promoted it (YapS127AB16F, P < .001; YapS127AB16F1, P = .017). Verteporfin, a direct YAP inhibitor, reduced cellular proliferation in B16F1 (P = .003) and B16F10 (P < .001) cells. Proliferative effects of nuclear YAP were confirmed in xenograft mice (P < .001). In conclusion, nuclear YAP in human melanomas showed subtype specificity and correlated with proliferative activity and proinvasiveness. It is expected that YAP becomes a useful prognostic marker, and its inhibition may be a potential therapy for melanoma patients.

Utility of next-generation sequencing in the diagnosis of metastatic melanoma: A case report.

During routine dermatologic examination, a 77-year-old male was noted to have a firm blue subcutaneous nodule on his right lateral upper back. His past medical history included metastatic melanoma of unknown primary involving right and left axillary lymph nodes, treated with ipilimumab/nivolumab with complete response, and subsequent primary uveal melanoma. The subcutaneous nodule was located near his previous right axillary scar for metastatic melanoma. Excision of the nodule showed a plexiform neoplasm involving mid and deep dermis composed of spindle and epithelioid atypical cells admixed with numerous melanophages. Central necrosis was present. Immunohistochemical studies revealed the tumor cells to be diffusely positive for HMB45, with retained expression of BAP1 and p16. The tumor cells were negative for PRAME, nuclear expression of ß-catenin, LEF1, and BRAF V600E. Molecular studies demonstrated BAP1 and GNA11 somatic mutations, a profile different from that exhibited by his prior melanoma. Collectively, these data were interpreted as a metastasis from uveal melanoma and not a recurrence of his metastatic likely cutaneous melanoma after complete response to immunotherapy. This case emphasizes the importance of molecular studies for definitive diagnosis in challenging clinical situations, especially when there is discordance among histopathological, immunohistochemical, and molecular studies. Integration of clinical, histopathological, and molecular features is warranted.

Spitz melanocytic neoplasms with MLPH::ALK fusions: Report of two cases with previously unreported features and literature review.

ALK-fused Spitz melanocytic neoplasms are a distinct subgroup of melanocytic lesions exhibiting unique histopathologic characteristics. These lesions often manifest as exophytic or polypoid tumors, characterized by fusiform-to-epithelioid melanocytes arranged in a nested, fascicular, or plexiform growth pattern. Several fusion partners of the ALK gene have been identified in spitzoid melanocytic neoplasms, with TPM3 and DCTN1 being the most prevalent. Less common fusion partners include NPM1, TPR, CLIP1, GTF3C2, EEF2, MYO5A, KANK1, and EHBP1. The MLPH gene, which encodes melanophilin (MLPH), playing a crucial role in regulating skin pigmentation by acting as a linker between RAB27A and myosin Va during melanosome transport, has also recently been recognized as a rare fusion partner of ALK in Spitz melanocytic neoplasms. Currently, there exists a sparse documentation within English literature, illustrating a limited number of cases featuring MLPH::ALK fusion in Spitz melanocytic neoplasms. In this report, we present two additional cases, including a previously unreported instance of Spitz melanoma, contributing to the expanding knowledge on ALK-fused Spitz melanocytic neoplasms. In addition, we provide a comprehensive review of the clinical, histopathologic, and molecular features observed in documented cases with this novel fusion.

Nectin-4 expression in a subset of cutaneous adnexal carcinomas: A potential target for therapy with enfortumab vedotin.

BACKGROUND: Enfortumab vedotin (EV) is an antibody-drug conjugate directed against Nectin-4 that is used to treat urothelial carcinoma. Nectin-4 is inherently expressed in the skin and adnexal structures. Since therapeutic options for cutaneous adnexal carcinomas are limited, we sought to evaluate Nectin-4 expression in adnexal carcinomas and benign adnexal neoplasms to identify tumors that are potentially targetable with EV. METHODS: Eight sebaceous carcinomas (seven periocular and one lymph node metastasis), eight digital papillary adenocarcinomas, seven squamoid eccrine ductal carcinomas, eight poromas, eight trichilemmomas, and seven sebaceous adenomas were subjected to immunohistochemical staining for anti-Nectin-4 antibody. H-scores for Nectin-4 expression were calculated. RESULTS: Benign adnexal neoplasms had a significantly lower mean (±SD) Nectin-4 H-score (142.6 ± 39.1) than did the adnexal carcinomas (198 ± 90.8; p = 0.006). Nectin-4 was expressed in 91% (21/23) of adnexal carcinomas. Sebaceous carcinomas frequently exhibited high expression of Nectin-4 (88% [7/8]), with a mean (±SD) H-score (258.1 ± 58.4) significantly higher than those for digital papillary adenocarcinomas (197.5 ± 52.5; p = 0.035) and squamoid eccrine ductal carcinomas (131.4 ± 114.1; p = 0.031). Sebaceous carcinomas also had significantly higher H-scores than did sebaceous adenomas (186.4 ± 25.0; p = 0.013). CONCLUSIONS: Increased Nectin-4 expression in a subset of cutaneous adnexal carcinomas, particularly sebaceous carcinomas, reveals that EV is a potential therapeutic option for these tumors.

Apoptosis Pathway-Associated Proteins Are Frequently Expressed in Melanoma: A Study of 32 Cases With Focus on Acral Lentiginous Melanoma.

ABSTRACT: Acral lentiginous melanoma (ALM) is an aggressive type of cutaneous melanoma (CM) that arises on palms, soles, and nail units. ALM is rare in White population, but it is relatively more frequent in dark-skinned populations. There is an unmet need to develop new personalized and more effective treatments strategies for ALM. Increased expression of antiapoptotic proteins (ie, BCL2, MCL1) has been shown to contribute to tumorigenesis and therapeutic resistance in multiple tumor types and has been observed in a subset of ALM and mucosal melanoma cell lines in vivo and in vitro. However, little is known about their expression and clinical significance in patients with ALM. Thus, we assessed protein expression of BCL2, MCL1, BIM, and BRAF V600E by immunohistochemistry in 32 melanoma samples from White and Hispanic populations, including ALM and non-ALM (NALM). BCL2, MCL1, and BIM were expressed in both ALM and NALM tumors, and no significant differences in expression of any of these proteins were detected between the groups, in our relatively small cohort. There were no significant associations between protein expression and BRAF V600E status, overall survival, or ethnicity. In summary, ALM and NALM demonstrate frequent expressions of apoptosis-related proteins BCL2, MCL1, and BIM. Our findings suggest that patients with melanoma, including ALM, may be potential candidates for apoptosis-directed therapies.

Complete Response to Immunotherapy Using Pembrolizumab in a Patient With Conjunctival Squamous Cell Carcinoma With Nodal Metastasis.

A 92-year-old woman presented with a large bulbar conjunctival mass in the OD. She also had a palpable parotid mass which on fine needle aspiration biopsy confirmed to be metastatic squamous cell carcinoma. The conjunctival mass was biopsied to confirm the diagnosis of squamous cell carcinoma with positive programmed cell death ligand 1 expression and a high tumor mutation burden. She was treated with pembrolizumab and had complete resolution of the conjunctival mass and the associated parotid metastasis after just 2 cycles of treatment. This case underscores the promising role of immune checkpoint inhibitors in the treatment of conjunctival squamous cell carcinoma, especially when surgery is associated with significant ocular morbidity, in patients who may not be good surgical candidates, or in patients with metastasis.

Condyloma and coincidental epidermodysplasia verruciformis acanthoma positive for human papillomavirus-14 and -21.

Epidermodysplasia verruciformis (EDV) is a rare genodermatosis that predisposes individuals to persistent infection with ß-human papillomavirus (HPV) genotypes. The term EDV acanthoma may be applied to lesions with incidental findings of EDV-defining histopathological features without clinical signs of EDV. We report a case of HPV-14- and -21-positive EDV acanthoma arising in association with condyloma in a female patient with a history of low-grade squamous intraepithelial lesion of the cervix positive for high-risk HPV (non-16/18), chronic kidney disease, and systemic lupus erythematosus. The patient had no family or personal history of EDV, but the patient was on immunosuppressive therapy with mycophenolate mofetil and prednisone. A biopsy specimen from one of the perianal lesions revealed histopathologic changes consistent with EDV in the setting of condyloma. Molecular testing showed HPV-14 and -21, which supported the coexistence of condyloma with EDV acanthoma.

BRAF V600E immunohistochemistry as a useful tool in the diagnosis of melanomas with ambiguous morphologies and immunophenotypes.

We report three melanoma cases in which BRAF V600E immunohistochemistry (IHC) was valuable for diagnosis. Patient 1: In a patient with a history of primary melanoma on the chest and metastatic melanoma to right breast after undergoing multiple local and systemic therapies, a lung metastasis exhibited chondroid differentiation, aberrant myofibroblastic marker expression, and rare pancytokeratin positivity, without melanocytic marker expression. Patient 2: After targeted and immunotherapy for primary melanoma on the scalp as well as regional and distant metastatic melanoma, an omental metastasis showed CDX2-positive glandular structures that were negative for melanocytic markers. It was initially misdiagnosed as primary gastrointestinal adenocarcinoma. Patient 3: A patient with history of melanoma showing epithelioid morphology on the right thigh presented with multiple soft tissue nodules on skin, lymph nodes and internal organs after being lost to follow-up for 4 years. A biopsy specimen from the right thigh showed spindled cells with scattered pancytokeratin cocktail positivity and ambiguous staining for melanocytic markers. For melanomas with ambiguous morphologies and/or immunophenotypes in each of the three patients, BRAF V600E expression by IHC was maintained in both primary and metastatic melanoma specimens examined. These cases highlight the utility of BRAF V600E IHC in the diagnosis of melanoma.

Immunohistochemical expression of TRPS1 in mammary Paget disease, extramammary Paget disease, and their close histopathologic mimics.

BACKGROUND: Trichorhinophalangeal syndrome type 1 (TPRS1) expression has been found to be highly sensitive and specific for breast carcinomas. The frequency of TRPS1 expression in cutaneous neoplasms such as mammary Paget disease (MPD) and extramammary PD (EMPD) is currently unknown. We assessed the utility of TRPS1 immunohistochemistry (IHC) in the evaluation of MPD, EMPD, and their histopathologic mimics, squamous cell carcinoma in situ (SCCIS) and melanoma in situ (MIS). METHODS: Twenty-four MPDs, 19 EMPDs, 13 SCCISs, and 9 MISs were subjected to immunohistochemical analysis using anti-TRPS1 antibody. The intensity (none, 0; weak, 1+ ; moderate, 2+ ; strong, 3+ ) and proportion (<1%, absent; 1%-25%, focal; 26%-75%, patchy; >75%, diffuse) of TRPS1 expression were recorded. Relevant clinical data were documented. RESULTS: TPRS1 expression was present in 100% (24/24) of MPDs, with 88% (21/24) of MPDs exhibiting strong, diffuse immunoreactivity. Sixty-eight percent (13/19) of EMPDs showed TRPS1 expression. Intriguingly, EMPDs lacking TRPS1 expression were consistently of perianal origin. TRPS1 expression was seen in 92% (12/13) of SCCISs but was absent in all MISs. CONCLUSIONS: TRPS1 may be useful to distinguish MPDs/EMPDs from MISs, but its utility is limited in distinguishing them from other pagetoid intraepidermal neoplasms such as SCCISs.

Telomerase reverse transcriptase immunohistochemical expression is sensitive but not specific for TERT gene amplification in acral melanoma.

BACKGROUND: TERT gene amplification (TGA) is a mechanism of telomerase reverse transcriptase (TERT) upregulation frequently utilized by acral melanomas (AMs). Currently, the utility of TERT immunohistochemistry (IHC) to predict TGA status in AMs is poorly documented. METHODS: AMs (26 primary and 3 metastatic) and non-acral cutaneous melanomas (6 primary) were subjected to immunohistochemical analysis using anti-TERT antibody to demonstrate protein expression and fluorescence in situ hybridization (FISH) to assess genomic copy number alteration. The relationship between TERT immunoreactivity and TGA confirmed by FISH was assessed using logistic regression. RESULTS: TERT expression was seen in 50% (13/26) of primary and 100% (3/3) of metastatic AMs and 50% (3/6) of primary non-acral cutaneous melanomas. TGA was found in 15% (4/26) and 67% (2/3) of primary and metastatic AMs and 17% (1/6) of non-acral cutaneous melanomas. The intensity of TERT immunoreactivity correlated with TGA (p = 0.04) and a higher TERT copy number-to-control ratio in AMs, with a correlation coefficient of 0.41 (p = 0.03). The sensitivity and specificity of TERT immunoreactivity for predicting TGA in AMs were 100% and 57%, with corresponding positive and negative predictive values of 38% and 100%, respectively. CONCLUSIONS: The clinical utility of TERT IHC to predict TGA status in AMs appears to be limited given its low specificity and positive predictive value.

Ductal differentiation: A rare phenomenon in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that may occasionally present divergent histopathologic features. We present two cases of MCC demonstrating ductal differentiation, one on the lower lip of an 81-year-old man and another on the right forearm of a 67-year-old man. The histopathologic features included TTF1-negative, infiltrative, high-grade basaloid tumor with paranuclear punctate positivity for cytokeratin (CK) 20 and synaptophysin. Rare luminal structures lined by atypical epithelioid cells positive for CEA and CK19 were noted, confirming the presence of ductal differentiation. Although the ductal differentiation is unusual, other histopathologic features and the immunohistochemical profile supported the diagnosis of MCC. Like most divergent features, ductal differentiation is rare in MCC and typically constitutes a very small proportion of the tumor, and is therefore under-recognized. Although the clinical significance of this feature is unclear, recognition and documentation of ductal differentiation and distinguishing it from other mimics such as acantholysis within squamous nests and entrapped eccrine ducts is essential to determine its clinical significance. We also discuss the differential diagnoses of cutaneous basaloid neoplasms with ductal differentiation.

The diverse landscape of dermatologic toxicities of non-immune checkpoint inhibitor monoclonal antibody-based cancer therapy.

BACKGROUND: Since their first approval 25 years ago, monoclonal antibodies (mAbs) have become important targeted cancer therapeutics. However, dermatologic toxicities associated with non-immune checkpoint inhibitor (non-ICI) mAbs may complicate the course of cancer treatment. Data on the incidence and types of these reactions are limited. METHODS: A comprehensive review was conducted on dermatologic toxicities associated with different classes of non-ICI mAbs approved for treatment of solid tumors and hematologic malignancies. The review included prospective Phase 1, 2, and 3 clinical trials; retrospective literature reviews; systematic reviews/meta-analyses; and case series/reports. RESULTS: Dermatologic toxicities were associated with several types of non-ICI mAbs. Inflammatory reactions were the most common dermatologic toxicities, manifesting as maculopapular, urticarial, papulopustular/acneiform, and lichenoid/interface cutaneous adverse events (cAEs) with non-ICI mAbs. Immunobullous reactions were rare and a subset of non-ICI mAbs were associated with the development of vitiligo cAEs. CONCLUSION: Dermatologic toxicities of non-ICI mAbs are diverse and mostly limited to inflammatory reactions. Awareness of the spectrum of the histopathologic patterns of cAE from non-ICI mAbs therapy is critical in the era of oncodermatology and oncodermatopathology.

Lymphomatoid papulosis with DUSP22-IRF4 rearrangement: A case report and literature review.

Lymphomatoid papulosis (LyP) with DUSP22-IRF4 rearrangement is a rare, recently described variant of LyP histopathologically characterized by a biphasic growth pattern, with epidermotropic small-to-medium-sized atypical T-cells and dermal large and transformed T-cells diffusely expressing CD30. LyP with DUSP22-IRF4 rearrangement can mimic other cutaneous lymphoproliferative disorders, particularly primary cutaneous anaplastic large cell lymphoma (PCALCL) or transformed mycosis fungoides (MF). Unlike PCALCL or transformed MF, LyP with DUSP22-IRF4 rearrangement shows an indolent clinical behavior, with frequent spontaneous regression of untreated lesions. Thus, it is important to recognize this rare variant of LyP to avoid misclassification, which may potentially lead to unnecessarily aggressive patient management. To our knowledge, only 13 cases of LyP with DUSP22-IRF4 rearrangement have been reported to date in the English literature. Herein, we describe an additional case of LyP with DUSP22-IRF4 rearrangement in a 63-year-old man and provide a comprehensive literature review with regards to the clinical, histopathologic, and molecular features of this novel entity.

Gene expression profiling and multiplex immunofluorescence analysis of bullous pemphigoid immune-related adverse event reveal upregulation of toll-like receptor 4/complement-induced innate immune response and increased density of TH 1 T-cells.

BACKGROUND: Immune checkpoint inhibitor (ICI)-based cancer therapies cause a variety of cutaneous immune-related adverse events (irAEs) including immunobullous skin eruptions like bullous pemphigoid (BP). However, little is known about the underlying immunopathogenic drivers of these reactions, and understanding the unique gene expression profile and immune composition of BP-irAE remains a critical knowledge gap in the field of oncodermatology/oncodermatopathology. METHODS: BP-irAE (n = 8) and de novo BP control (n = 8) biopsy samples were subjected to gene expression profiling using the NanoString® Technologies nCounter PanCancer Immune Profiling Panel. Multiplex immunofluorescence (mIF) studies using markers for T-cells (CD3 and CD8), T helper 1 (TH 1) cells (Tbet), TH 2 cells (Gata3), TH 17 cells (RORγT), and regulatory T-cells (Tregs; FoxP3) were further evaluated using InForm® image analysis. RESULTS: Compared with de novo BP controls, BP-irAE samples exhibited upregulation of 30 mRNA transcripts (p < 0.025), including toll-like receptor 4 (TLR4) and genes associated with complement activation, and downregulation of 89 mRNA transcripts (p < 0.025), including genes associated with TH 2, TH 17, and B-cell immune response. BP-irAE demonstrated a greater density of Tbet+ (TH 1) cells in the dermis (p = 0.004) and fewer Tregs in the blister floor (p = 0.028) when compared with that of de novo control BP samples. CONCLUSIONS: BP-irAE exhibited activation of the TLR4/complement-driven classical innate immune response pathway, with dermal TH 1 immune cell polarization and decreased Tregs in the blister floor. TLR/complement signaling may underlie the immunopathogenesis of BP-irAE.

Pityriasis Rubra Pilaris After Moderna COVID-19 Vaccination: A Case Report and Literature Review.

ABSTRACT: To date, over 60% of the world's population has received at least 1 dose of coronavirus disease 2019 (COVID-19) vaccination, with over 12 billion doses administered globally. Commonly reported adverse effects of COVID-19 vaccination include fever, headache, myalgia, and injection site reactions. The spectrum of documented cutaneous reactions after COVID-19 vaccination is broad; however, pityriasis rubra pilaris (PRP) or PRP-like eruption secondary to COVID-19 vaccine is exceedingly rare, with only 17 cases previously reported to date in the English literature. In this article, we describe an additional case of COVID-19 vaccination-associated PRP in a 50-year-old woman with a history of metastatic breast carcinoma, who developed a widespread cutaneous eruption characteristic of PRP, including palmoplantar keratoderma, 10 days after her third dose of Moderna COVID-19 vaccine. Punch biopsy specimen showed epidermal hyperplasia with overlying hyperkeratosis, alternating orthokeratosis and parakeratosis and focal follicular plugging, supporting the diagnosis of PRP. The patient improved within weeks of initiating oral acitretin and topical steroids, with resolution achieved after 3 months of continued therapy. To the best of our knowledge, this is the third reported case of Moderna COVID-19 vaccination-associated PRP and collectively the 18 th after the administration of all COVID-19 vaccines currently available, including Pfizer-BioNTech, and AstraZeneca.

PRAME and LEF1 in Combined Deep Penetrating Nevus and Combined Blue Nevus: Utility and Pitfalls.

ABSTRACT: Deep penetrating nevi (DPN), particularly those showing combined features, or combined deep penetrating nevi (CDPN), may show histopathological resemblance to blue nevus (BN) and melanoma. Preferentially Expressed Antigen in MElanoma (PRAME) is a marker that helps distinguish melanoma from benign melanocytic lesions. Lymphoid enhancer-binding factor 1 (LEF1) has been proposed to be used in conjunction with ß-catenin for diagnosis of DPN. The immunohistochemical expression of PRAME and LEF1 was evaluated in 10 DPN (including 6 CDPN and 2 DPN-like proliferations with atypical features), 16 BN (including combined and cellular BN), and 2 melanomas with features of DPN or BN. PRAME was negative in most DPN (n = 10/10, n = 9/10, one case with discrepancy between readers) and all BN (n = 16/16), while the 2 melanomas included were positive (n = 2/2). All DPN were positive for LEF1 (n = 9/9) while only a subset of BN were positive (n = 6/16, P = 0.0028; n = 5/16, P = 0.001, per both readers). LEF1 seemed to be easier to interpret than ß-catenin because of its nuclear pattern of expression. The expression of LEF1 in the regular nevus component of combined BN presents a potential pitfall in practice because it may lead to misinterpretation of LEF1 as positive in the BN component of the lesion. However, a subset (approximately one-third) of combined BN seemed to show true LEF1 expression. Taking into account pitfalls in interpretation, the combinatorial panel of PRAME and LEF1, in addition to conventional histopathological features, may be useful to distinguish CDPN from combined BN and other benign and malignant mimics.

T-Cell Lymphomas, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase-negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.

Eosinophilic homogeneous intracytoplasmic inclusion bodies: Unique viral cytopathic changes associated with epidermodysplasia verruciformis and human papillomavirus type 49.

Epidermodysplasia verruciformis (EDV) is a rare genodermatosis that predisposes affected individuals to persistent infection with certain types of human papillomavirus (HPV), particularly those that belong to the genus beta-HPV, including HPV-5 and HPV-8, which carry high oncogenic potential. There are three main HPV-related viral cytopathic changes in cutaneous verrucae in terms of intracytoplasmic inclusion bodies (ICBs), namely, granular, filamentous, and homogeneous type ICBs. To date, only HPV-4, HPV-60, and HPV-65 have been found in association with homogeneous ICBs. We report a unique case of HPV-49-associated EDV in a 41-year-old woman with common variable immunodeficiency, mycosis fungoides, and multiple cutaneous malignancies, including squamous cell carcinoma and Merkel cell carcinoma who presented with multiple pink papules and hyperpigmented macules on the left upper extremity. One of the skin lesions histopathologically revealed keratinocytic nuclear enlargement with abundant blue-gray cytoplasm, accompanied by hypergranulosis, characteristic of EDV, along with peculiar bright eosinophilic and homogeneous ICBs. To the best of our knowledge, this is the first reported case of EDV with detection of HPV-49 by genotyping, which features eosinophilic homogeneous ICBs, like those seen in the setting of HPV-4, HPV-60, or HPV-65 infection.