RESUMO
This case series describes a constellation of novel adverse reactions in 3 of 9 patients with uveal melanoma receiving treatment targeting activity of the Brahma-associated factor chromatin remodeling complex.
Assuntos
Melanoma , Neoplasias Uveais , Humanos , Melanoma/patologia , Neoplasias Uveais/patologia , Neoplasias Uveais/genética , Doença de Darier/diagnóstico , Doença de Darier/patologia , Sobrancelhas/anormalidades , Montagem e Desmontagem da Cromatina , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Transcrição/genética , Anormalidades MúltiplasRESUMO
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.
Assuntos
Apoptose , Proteína 11 Semelhante a Bcl-2 , Biomarcadores Tumorais , Melanoma , Proteína de Sequência 1 de Leucemia de Células Mieloides , Proteínas Proto-Oncogênicas c-bcl-2 , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Masculino , Melanoma/patologia , Melanoma/genética , Melanoma/metabolismo , Feminino , Pessoa de Meia-Idade , Idoso , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína 11 Semelhante a Bcl-2/metabolismo , Proteína 11 Semelhante a Bcl-2/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Imuno-Histoquímica , Idoso de 80 Anos ou maisRESUMO
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.
Assuntos
Quinase do Linfoma Anaplásico , Melanoma , Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Adulto , Feminino , Humanos , Proteínas Adaptadoras de Transdução de Sinal , Quinase do Linfoma Anaplásico/genética , Melanoma/genética , Melanoma/patologia , Nevo de Células Epitelioides e Fusiformes/genética , Nevo de Células Epitelioides e Fusiformes/patologia , Proteínas de Fusão Oncogênica/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
Granulomatous Mycosis Fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by a granulomatous infiltrate associated with the neoplastic lymphoid population and is considered to have a worse prognosis compared with regular MF. The upregulation of the T helper (Th) axis, especially Th17, plays an important role in the pathogenesis of several inflammatory/infectious granulomatous cutaneous diseases, but its role in GMF is still not elucidated to date. In this study, we evaluated the immunohistochemical expression of Th1 (Tbet), Th2 (GATA-3), Th17 (RORγT), T regulatory (Foxp3), and immune checkpoint (IC) (PD-1 and PD-L1) markers in a cohort of patients with GMF and MF with large cell transformation (MFLCT). Skin biopsies from 49 patients (28 GMF and 21 MFLCT) were studied. Patients with GMF were associated with early clinical stage (p = 0.036) and lower levels of lactate dehydrogenase (p = 0.042). An increased percentage of cells positive for Tbet (p = 0.017), RORγT (p = 0.001), and PD-L1 (p = 0.011) was also observed among the GMF specimens, while a stronger PD-1 intensity was detected in cases of MFLCT. In this cohort, LCT, RORγT < 10%, Foxp3 < 10%, age, and advanced stage were associated with worse overall survival (OS) in univariate analysis. GMF demonstrated Th1 (cellular response) and Th17 (autoimmunity) phenotype, seen in early MF and granulomatous processes, respectively, which may be related to the histopathological appearance and biological behavior of GMF. Further studies involving larger series of cases and more sensitive techniques are warranted.
Assuntos
Micose Fungoide , Neoplasias Cutâneas , Humanos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Neoplasias Cutâneas/patologia , Antígeno B7-H1/metabolismo , Regulação para Cima , Receptor de Morte Celular Programada 1/metabolismo , Fator de Maturação da Glia/metabolismo , Micose Fungoide/patologia , Fatores de Transcrição Forkhead/metabolismoRESUMO
BACKGROUND: Although trichorhinophalangeal syndrome type 1 (TRPS1) was initially thought to be highly sensitive and specific for carcinomas and mesenchymal tumors of mammary origin, more recent data suggest its expression is not limited to breast neoplasms but also can be seen in other cutaneous neoplasms, such as extramammary Paget disease and squamous cell carcinoma (SCC) in situ. METHODS: Two-hundred cases of non-melanocytic cutaneous neoplasm, including basal cell carcinomas (BCCs) (n = 41), SCCs (n = 35), Merkel cell carcinomas (MCCs) (n = 25), and adnexal neoplasms (n = 99), were tested for TRPS1 expression using a monoclonal anti- TRPS1 rabbit anti-human antibody. RESULTS: TRPS1 expression was present in almost all cases of SCC (94%), with a median H-score of 200, while it was either absent or only focally present in most BCCs (90%), with a median H-score of 5. The difference between BCCs and SCCs in H-score was significant (p < .001). All MCCs (100%) lacked TRPS1 expression. TRPS1 expression was frequently seen in most adnexal neoplasms, benign and malignant, in variable intensity and proportion but was consistently absent in apocrine carcinomas. All endocrine mucin-producing sweat gland carcinomas (EMPSGCs) (100%, 6/6) showed diffuse and strong TRPS1 immunoreactivity, with a median H-score of 300, which was significantly different (p < .001) than that of BCCs. CONCLUSIONS: Our study shows that TRPS1 may be an effective discriminatory marker for BCCs and SCCs. It also has a role in distinguishing BCCs from EMPSGCs.
RESUMO
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.
Assuntos
Adenocarcinoma Papilar , Anticorpos Monoclonais , Nectinas , Neoplasias de Anexos e de Apêndices Cutâneos , Neoplasias Cutâneas , Humanos , Adenoma , Carcinoma Ductal , Carcinoma de Apêndice Cutâneo , Carcinoma de Células de Transição , Neoplasias de Anexos e de Apêndices Cutâneos/tratamento farmacológico , Neoplasias das Glândulas Sebáceas/patologia , Neoplasias Cutâneas/patologia , Neoplasias das Glândulas Sudoríparas/tratamento farmacológicoRESUMO
Extramammary Paget disease (EMPD) predominantly manifests de novo as primary EMPD, with less than 30 % of cases associated with underlying internal malignancy (secondary EMPD). Differentiating primary from secondary EMPDs based solely on histopathology poses challenges, often necessitating supplementary screening, such as endoscopy or imaging studies, to definitively exclude underlying carcinomas like colonic adenocarcinoma. Recently, TRPS1 immunohistochemistry, initially identified as a sensitive and specific marker for carcinomas and mesenchymal tumors of mammary origin, has been proposed for EMPD. In this study, we conducted a systematic assessment of TRPS1 expression across 93 EMPD cases, comprising 82 primary EMPDs and 11 secondary EMPDs. Our aim was to assess the potential utility of TRPS1 as a marker to differentiate between primary and secondary EMPDs. Our findings revealed that 88 % (72/82) of primary EMPDs displayed TRPS1 expression, while secondary EMPDs consistently lacked TRPS1 expression (100 %; 11/11). Within the primary EMPD group, consistent TRPS1 immunoreactivity was observed in lesions originating outside the perianal region, such as the groin/inguinal area, axilla, and trunk. Interestingly, a majority (91 %; 10/11) of primary EMPDs originating in the perianal region exhibited an absence of TRPS1 expression. Upon excluding cases of perianal primary EMPDs, the sensitivity and specificity of TRPS1 for primary EMPDs reached 100 %. Our findings suggest that TRPS1 expression holds notable sensitivity and specificity for primary EMPDs, particularly when arising from non-perianal cutaneous sites. Hence, in suitable clinical contexts, TRPS1 immunohistochemistry may emerge as a promising and valuable tool for distinguishing primary and secondary EMPDs.
Assuntos
Doença de Paget Extramamária , Neoplasias Cutâneas , Humanos , Doença de Paget Extramamária/diagnóstico , Doença de Paget Extramamária/patologia , Imuno-Histoquímica , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Proteínas RepressorasRESUMO
BACKGROUND: Changes in immunophenotype in mycosis fungoides (MF) are rarely reported, making this phenomenon a diagnostic challenge with unclear significance for the disease's biological behavior. This study examines a large series of MF patients who exhibited a phenotype switch (PS) and analyzes their clinical and histopathologic characteristics. DESIGN: Institutional files were searched for MF cases exhibiting PS between 2010 and 2020. Clinical, follow-up, and histopathological data were collected. RESULTS: Forty-two biopsies from 32 patients (13 women and 19 men, median age 67.5) showed PS. Eight patients (25 %) experienced multiple PS during their disease course. The median time for PS was 22 months from the initial diagnosis. In 5 cases tested, identical TCR clone peaks were detected in the immunophenotypically distinct lesions. Median follow-up was 14.5 months. Among deceased patients, median time from MF diagnosis to PS was 20.6 months, while among the patients who were still alive, median time was 44.1 months. CONCLUSION: MF biopsies can show PS during the course of the disease and may indicate a change in clinical behavior. 28.1 % of patients displayed more than one PS, further indicating high plasticity of MF cells. No obvious association was found between PS and therapy initiation or response. Features that appeared to portend a worse clinical course were earlier PS in the course of the disease and PS from CD4-/CD8-to CD8+, and CD8+ to CD4-/CD8-. Awareness of this phenomenon is crucial to avoid misdiagnosing phenotypically distinct lymphomas as second primaries and to alert clinicians about potential changes in the disease's clinical course.
Assuntos
Micose Fungoide , Neoplasias Cutâneas , Masculino , Humanos , Feminino , Idoso , Neoplasias Cutâneas/patologia , Micose Fungoide/terapia , Micose Fungoide/diagnóstico , Micose Fungoide/patologia , Fenótipo , Biópsia , Progressão da DoençaRESUMO
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.
Assuntos
Melanoma , Nevo Azul , Nevo de Células Epitelioides e Fusiformes , Nevo , Neoplasias Cutâneas , Humanos , Nevo Azul/diagnóstico , Nevo Azul/patologia , beta Catenina/metabolismo , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Fator 1 de Ligação ao Facilitador Linfoide , Melanoma/patologia , Nevo de Células Epitelioides e Fusiformes/diagnóstico , Nevo/diagnóstico , Nevo/patologia , Fatores de Transcrição , Diagnóstico Diferencial , Antígenos de NeoplasiasRESUMO
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.
Assuntos
Melanoma , Neoplasias Cutâneas , Telomerase , Humanos , Amplificação de Genes , Hibridização in Situ Fluorescente , Telomerase/genética , Telomerase/metabolismo , Mutação , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Melanoma/diagnóstico , Melanoma/genética , Melanoma/metabolismo , Melanoma Maligno CutâneoRESUMO
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.
Assuntos
Penfigoide Bolhoso , Humanos , Vesícula/metabolismo , Proteínas do Sistema Complemento , Imunofluorescência , Perfilação da Expressão Gênica , Imunidade Inata , Penfigoide Bolhoso/patologia , RNA Mensageiro , Receptor 4 Toll-Like/metabolismo , Regulação para CimaRESUMO
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.
Assuntos
Papulose Linfomatoide , Micose Fungoide , Neoplasias Cutâneas , Masculino , Humanos , Pessoa de Meia-Idade , Papulose Linfomatoide/genética , Papulose Linfomatoide/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Micose Fungoide/patologia , Linfócitos T/patologia , Antígeno Ki-1 , Fosfatases de Especificidade Dupla/genética , Fosfatases da Proteína Quinase Ativada por Mitógeno/genéticaRESUMO
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.
Assuntos
Doença de Paget Extramamária , Doença de Paget Mamária , Proteínas Repressoras , Feminino , Humanos , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Imuno-Histoquímica , Doença de Paget Extramamária/diagnóstico , Doença de Paget Extramamária/metabolismo , Doença de Paget Extramamária/patologia , Doença de Paget Mamária/diagnóstico , Doença de Paget Mamária/metabolismo , Doença de Paget Mamária/patologia , Proteínas Repressoras/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
CONTEXT.: Distinction between Merkel cell carcinoma (MCC) and pulmonary small cell carcinoma (PSmCC) can be challenging, even with the aid of immunohistochemistry (IHC) analysis of CK20 and TTF1, as these tumors occasionally lack classic immunophenotypes (CK20+/TTF1- in MCC and CK20-/TTF1+ in PSmCC). OBJECTIVE.: To evaluate the diagnostic utility of SOX11 and PAX5 IHC for distinguishing MCCs from PSmCCs and compare it with that of CK20 and TTF1 IHC. DESIGN.: SOX11, PAX5, CK20, and TTF1 expression (pattern, intensity, and proportion of tumor cells expressing protein) was assessed in 31 primary and 16 metastatic MCCs and 20 primary and 9 metastatic PSmCCs. RESULTS.: SOX11 expression was present in all MCCs and was predominantly strong and diffuse. Only 19% of primary and 38% of metastatic MCCs exhibited diffuse PAX5 expression; none exhibited strong immunoreactivity. Strong and diffuse SOX11 expression was seen in less than 25% of primary and metastatic PSmCCs. PAX5 expression was rare in PSmCCs and was mostly weak and focal/patchy. SOX11 expression in at least 26% of tumor cells, with at least moderate intensity, favored the diagnosis of MCC over PSmCC (P < .001). Furthermore, SOX11 expression was more likely than CK20 expression to be strong or diffuse in sentinel lymph node (SLN) metastases of MCC, indicating that SOX11 is superior to CK20 for detecting tumor deposits in SLNs in MCC. CONCLUSIONS.: Our findings indicate that SOX11 not only is a powerful marker for distinguishing MCCs from PSmCCs, especially when used in conjunction with CK20 and TTF1, but also has utility for screening SLNs in MCC.
Assuntos
Carcinoma de Célula de Merkel , Carcinoma de Células Pequenas , Neoplasias Pulmonares , Neoplasias Cutâneas , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Célula de Merkel/diagnóstico , Carcinoma de Célula de Merkel/metabolismo , Carcinoma de Célula de Merkel/patologia , Neoplasias Cutâneas/patologia , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Biomarcadores Tumorais/análise , Fatores de Transcrição SOXC , Fator de Transcrição PAX5 , Proteínas de Ligação a DNA , Fatores de TranscriçãoRESUMO
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.
Assuntos
Carcinoma de Célula de Merkel , Neoplasias Cutâneas , Masculino , Humanos , Idoso de 80 Anos ou mais , Idoso , Carcinoma de Célula de Merkel/diagnóstico , Carcinoma de Célula de Merkel/patologia , Neoplasias Cutâneas/patologia , Diagnóstico Diferencial , Diferenciação CelularRESUMO
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.
Assuntos
Acantoma , Condiloma Acuminado , Epidermodisplasia Verruciforme , Infecções por Papillomavirus , Neoplasias Cutâneas , Humanos , Feminino , Acantoma/complicações , Papillomavirus Humano , Epidermodisplasia Verruciforme/complicações , Epidermodisplasia Verruciforme/patologia , Infecções por Papillomavirus/patologia , Condiloma Acuminado/complicações , Papillomaviridae , Neoplasias Cutâneas/complicaçõesRESUMO
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.
Assuntos
Antineoplásicos Imunológicos , Toxidermias , Neoplasias , Humanos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos Retrospectivos , Estudos Prospectivos , Antineoplásicos Imunológicos/uso terapêutico , Toxidermias/patologia , Neoplasias/tratamento farmacológicoRESUMO
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.