RESUMEN
Crystal-storing histiocytosis (CSH) is a rare condition in which crystals accumulate in the cytoplasm of histiocytes and is usually associated with a lymphoplasmacytic neoplasm. Cutaneous CSH is extraordinarily rare and limited to case reports in the literature. We report two cases of this disease with cutaneous involvement. Case 1 was a 65-year-old male with a 4-month history of a pruritic eruption that started as a solitary pink to skin-colored indurated plaque on the anterior neck before progressing to involve the whole neck, chest wall, and face. Case 2 was a 54-year-old woman with a history of unspecified "lymphoma" who presented with a soft nodule on the forearm. Biopsies from both cases had similar findings and showed a proliferation of epithelioid cells with pink cytoplasm and intracellular crystalline structures infiltrating the dermis and subcutaneous fat. In the first case, the cells were positive for CD43, CD45, CD68, and IgG kappa, and in the second case, the crystals were positive for IgG lambda. Based on these findings, the patients were diagnosed with cutaneous CSH. We highlight this rare diagnosis and the importance of investigating an underlying lymphoplasmacytic neoplasm.
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Histiocitosis , Humanos , Anciano , Masculino , Femenino , Histiocitosis/patología , Histiocitosis/metabolismo , Persona de Mediana Edad , Histiocitos/patología , Histiocitos/metabolismo , Cristalización , Enfermedades de la Piel/patología , Enfermedades de la Piel/metabolismoRESUMEN
OBJECTIVES: Cutaneous diseases that disproportionately affect patients with darker pigmentation and their histologic features are historically understudied and undertreated. This review article aims to highlight the key clinical features, histopathology, and diagnostic pearls of several cutaneous diseases that commonly present in patients with darker pigmentation. METHODS: A literature search was conducted, and a list of cutaneous diseases that frequently affect patients with darker pigmentation was compiled. A group of experts expounded upon those that were most common or misdiagnosed according to scientific evidence and clinical practice. RESULTS: The diseases were divided into hypopigmented disorders, hyperpigmented disorders, scarring disorders, and alopecic disorders. Within each category, the etiology, clinical features, histopathology, and key histologic differential diagnoses are described and discussed. CONCLUSIONS: As many clinicians are taught that there are no effective treatment options or that these diseases are considered "cosmetic" in nature, patients often do not get a thorough medical workup or skin biopsy. This article aims to decrease the knowledge gap and serve as a resource for anyone involved in the care of patients with these cutaneous conditions.
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Enfermedades de la Piel , Pigmentación de la Piel , Humanos , Enfermedades de la Piel/patología , Enfermedades de la Piel/diagnóstico , Trastornos de la Pigmentación/patología , Trastornos de la Pigmentación/diagnóstico , Diagnóstico Diferencial , Hiperpigmentación/patología , Hiperpigmentación/diagnósticoRESUMEN
Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis that preferentially involves long bones but can affect a variety of other organs. Initial presentation with extraskeletal involvement is not unusual and is most commonly observed in the central nervous system, heart, retroperitoneum, lungs, and skin. Initial presentation of the disease as a subcutaneous soft tissue mass is exceedingly rare and may pose difficulties for diagnosis. We describe a case of Erdheim-Chester disease that initially presented as a cutaneous and subcutaneous soft tissue mass in the right posterior shoulder of a 52-year-old man.
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Enfermedad de Erdheim-Chester , Enfermedad de Erdheim-Chester/patología , Humanos , Masculino , Persona de Mediana Edad , Piel/patología , Enfermedades de la Piel/patologíaRESUMEN
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.
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Micosis Fungoide , Neoplasias Cutáneas , Masculino , Humanos , Femenino , Anciano , Neoplasias Cutáneas/patología , Micosis Fungoide/terapia , Micosis Fungoide/diagnóstico , Micosis Fungoide/patología , Fenotipo , Biopsia , Progresión de la EnfermedadRESUMEN
MC1R, a G-protein coupled receptor, triggers ultraviolet light-induced melanin synthesis and DNA repair in melanocytes and is implicated in the pathogenesis of melanoma. Although widely expressed in different tissue types, its function in non-cutaneous tissue is relatively unknown. Herein, we demonstrate that disruptive MC1R variants associated with melanomagenesis are less frequently found in patients with several cancers. Further exploration revealed that breast cancer tissue shows a significantly higher MC1R expression than normal breast tissue, and knocking down MC1R significantly reduced cell proliferation in vitro and in vivo. Mechanistically, MC1R signaling through the MC1R-cAMP-CREB/ATF-1 and MC1R-ERK-NFκB axes accelerated the G1-S transition in breast cancer cells. Our results revealed a new association between MC1R and breast cancer, which could be potentially targeted therapeutically. Moreover, our results suggest that MC1R-enhancing/activating therapies should be used cautiously, as they might be pro-tumorigenic in certain contexts.
RESUMEN
Subcutaneous leiomyosarcoma (LMS) is a rare, poorly understood variant. The current literature on the subject is sparse, consisting of isolated case reports and small clinicopathologic studies compromised by the inclusion of both its more common and indolent counterpart, cutaneous LMS (atypical intradermal smooth muscle neoplasm), as well as highly aggressive deep-seated tumors. Thus, precise clinicopathologic characterization is limited. Cases of subcutaneous LMS reviewed at the University of Michigan and Cleveland Clinic from 1994 to 2022 were included in this retrospective study. A total of 39 cases were identified. The mean age was 61 years, and the cohort was predominantly male (23/39; 59%). Tumors averaged 4.2 cm and most commonly arose on the extremities (32/39; 82%). The majority (38/39; 97%) were diagnosed at an early pathologic stage (pT1 or pT2). Histopathologically, most tumors were well-circumscribed and were assigned a Fédération Nationale des Centers de Lutte Contre le Cancer grade of either 1 or 2 (24/39; 62%). The majority (22/39; 56%) appeared to arise in association with a blood vessel. Of the 36 cases with accessible clinical data and follow-up (mean 34 mo, range 0 to 94 mo), 12 (33%) were noted to have metastasized, with the lung representing the most common anatomic location. One case recurred locally. Six of 36 patients (17%) died from the disease at an average of 47 months after diagnosis (range 16 to 94 mo). Metastasis or death from disease was significantly associated with the Fédération Nationale des Centers de Lutte Contre le Cancer grade ( P =0.0015), the presence of necrosis ( P =0.032), tumor size ( P =0.049), and AJCC tumor stage ( P =0.036). These data demonstrate that subcutaneous LMS are more aggressive than dermal-based tumors and have a prognosis akin to that of deep-seated LMS.
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Leiomiosarcoma , Neoplasias Cutáneas , Humanos , Masculino , Persona de Mediana Edad , Femenino , Leiomiosarcoma/terapia , Leiomiosarcoma/patología , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Pronóstico , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/patologíaRESUMEN
Nipple adenoma (NA) is a rare, benign proliferation of the nipple ducts. It may be clinically mistaken for Paget disease or squamous cell carcinoma; thus, microscopic evaluation is paramount. A large case series of NA has not been undertaken since the 1980s. Therefore, we undertook this study to evaluate the clinicopathologic characteristics of NA, emphasizing differential diagnoses and follow-up data. We retrieved 50 cases from our in-house archives or consultation files between 2003 and 2022. Available slides were reviewed, and clinical data and follow-up information were obtained. Cases must have exhibited a dense ductal proliferation in the breast tissue with proximity to the nipple epidermis. All patients were women; median age was 56 years. In all, 68% of patients were symptomatic; 53% demonstrated a skin growth. Overall, 67% were excised completely, either primarily (33%) or via re-excision after biopsy (33%). Four histologic patterns were noted: adenosis (dense proliferation of small-to-medium ducts); large duct (medium-to-large caliber ducts); papillary-like (frond-like architecture with branching, slit-like lumens); and pseudoinfiltrative (ducts squished and distorted by dense stromal fibrosis). Follow-up in 44 patients (88%) with a median time of 66 months showed no evidence of recurrence. NA demonstrates a wide spectrum of histopathologic variation. Subtyping of this entity is unlikely to be clinically relevant. Differentiation from invasive carcinoma or other histologic mimics (syringocystadenoma papilliferum, syringomatous adenoma) may be difficult. Simple excision is curative, and recurrence is rare. A definitive link to invasive carcinoma has not been established.
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Adenocarcinoma , Adenoma , Neoplasias de la Mama , Humanos , Femenino , Persona de Mediana Edad , Masculino , Neoplasias de la Mama/patología , Adenoma/patología , Pezones/patología , Pezones/cirugía , Adenocarcinoma/patologíaRESUMEN
Pseudoxanthoma elasticum (PXE) is an autosomal recessive genetic disorder characterized by aberrant fragmentation and calcification of elastic fibers, leading to characteristic cutaneous, ophthalmic, and cardiovascular manifestations. PXE demonstrates significant phenotypic variability; involvement of the oral mucosa may be the only clue to the diagnosis. Reports on mucous membrane involvement in PXE are scarce. Here, we present a case of PXE-like changes in the oral cavity. A 70-year-old male patient presented with a painless leukoplakic lesion on the soft palate. Biopsy revealed numerous degenerated fibers in the lamina propria. Verhoeff-van Gieson and von Kossa staining confirmed their identity as calcified elastic fibers. A histopathological diagnosis of PXE-like changes was made; the patient was referred to ophthalmology where angioid streaks were visualized fundoscopically. PXE-like changes in the absence of the characteristic genetic mutation have also been reported with or without systemic manifestations. Furthermore, PXE-like changes have been reported in up to 10% of oral biopsy specimens undertaken without clinical suspicion for PXE. Therefore, the significance of such changes in isolation is unclear. Clinicians and pathologists should be aware of the potential oral manifestations of PXE to facilitate prompt diagnosis and subspecialist referral.
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Seudoxantoma Elástico , Masculino , Humanos , Anciano , Seudoxantoma Elástico/diagnóstico , Seudoxantoma Elástico/patología , Piel/patología , Tejido Elástico/patología , Paladar Blando/patología , MutaciónRESUMEN
BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) typically involves deep soft tissue (beneath the fascia) of the proximal extremities and trunk. Long-term follow-up has shown a high rate of local recurrence, metastasis, and death. To the best of our knowledge, there is only one previous large series focusing on superficial LGFMS suggesting superficial tumors are disproportionately more common in children and may have a better prognosis. Our study's primary goals are to confirm these findings and increase general awareness that LGFMS may arise in superficial soft tissue. METHODS: We retrieved our cases of superficial LGFMS diagnosed between 2008 and 2020. Available slides were reviewed, and clinical data and follow-up information were obtained. RESULTS: The patients included nine males and 14 females with a median age of 29 years; eight (35%) were children (<18 years) and five (22%) were young adults (18-30 years). The majority involved the lower extremities (65%). The tumors were primarily centered in the subcutis (91%) and dermis (9%). Microscopically, they had typical features of LGFMS with alternating fibrous and myxoid zones composed of bland, slightly hyperchromatic spindled cells. All were positive for MUC4 by immunohistochemistry and/or FUS rearrangement by FISH. Follow-up on 14 cases ranged from 11 to 148 months (median 61 months) with no evidence of recurrences or distant metastases. CONCLUSIONS: Compared to conventional deep-seated counterparts, superficial LGFMS is more likely to occur in the extremities of children and young adults and may have a better clinical outcome. Further studies with longer follow-up will likely help support these findings.
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Fibrosarcoma , Neoplasias de los Tejidos Blandos , Masculino , Femenino , Humanos , Neoplasias de los Tejidos Blandos/patología , Fibrosarcoma/patología , InmunohistoquímicaRESUMEN
BACKGROUND: Spitzoid melanocytic neoplasms are diagnostically challenging; criteria for malignancy continue to evolve. The ability to predict chromosomal abnormalities with immunohistochemistry (IHC) could help select cases requiring chromosomal evaluation. METHODS: Fluorescence in situ hybridization (FISH)-tested spitzoid neoplasms at our institution (2013-2021) were reviewed. p16, BRAF V600E, and preferentially expressed antigen in melanoma (PRAME) IHC results were correlated with FISH. RESULTS: A total of 174 cases (1.9F:1M, median age 28 years; range, 5 months-74 years) were included; final diagnoses: Spitz nevus (11%), atypical Spitz tumor (47%), spitzoid dysplastic nevus (9%), and spitzoid melanoma (32%). Sixty (34%) were FISH positive, most commonly with absolute 6p25 gain (RREB1 > 2). Dermal mitotic count was the only clinicopathologic predictor of FISH. Among IHC-stained cases, p16 was lost in 55 of 134 cases (41%); loss correlated with FISH positive (p < 0.001, Fisher exact test). BRAF V600E (14/88, 16%) and PRAME (15/56, 27%) expression did not correlate with FISH alone (p = 0.242 and p = 0.359, respectively, Fisher exact test). When examined together, however, p16-retained/BRAF V600E-negative lesions had low FISH-positive rates (5/37, 14%; 4/37, 11% not counting isolated MYB loss); all other marker combinations had high rates (56%-75% of cases; p < 0.001). CONCLUSIONS: p16/BRAF V600E IHC predicts FISH results. "Low-risk" lesions (p16+ /BRAF V600E- ) uncommonly have meaningful FISH abnormalities (11%). PRAME may have limited utility in this setting.
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Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Hibridación Fluorescente in Situ , Melanoma/diagnóstico , Melanoma/genética , Melanoma/metabolismo , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Aberraciones Cromosómicas , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Diagnóstico Diferencial , Antígenos de NeoplasiasRESUMEN
ABSTRACT: An unusual benign skin lesion is reported in a 19-year-old man with no significant medical history. The lesion had been present since he was an infant and had been slowly enlarging over the past 15 years. The lesion caused pain and discomfort, and the patient underwent an excisional biopsy. Histologic examination showed a subcutaneous lesion with ill-defined borders and peripheral areas of infiltration between adnexal structures. The lesion was composed of small round to ovoid cells embedded in a collagenous stroma with prominent cystic pseudovascular appearing channels causing a pseudopapillary or lymphangitic appearance that mimicked a vascular neoplasm. Immunohistochemistry performed showed positive staining for EMA, progesterone receptor, D2-40, and vimentin within the lesional cells. The tumor cells were negative for cytokeratin AE1/AE3, CD34, CD31, HHV-8, STAT6, SMA, Desmin, S-100, Melan A, and HMB45. A next-generation sequencing study using a hybrid capture-based panel examining 50 commonly mutated genes in human neoplasia was performed and showed no molecular alterations suggesting a nonneoplastic nature. Based on the clinical presentation, histologic features, and results of ancillary studies, the case was diagnosed as a hamartoma of the scalp with meningothelial-like elements. Reported cases of this lesion have behaved in a benign manner; however, as the histologic differential includes low-grade malignant vascular neoplasms such as angiosarcoma, it is important to recognize the salient features of this lesion.
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Hamartoma , Hemangiosarcoma , Neoplasias Vasculares , Adulto , Diagnóstico Diferencial , Hamartoma/patología , Hemangiosarcoma/patología , Humanos , Inmunohistoquímica , Masculino , Cuero Cabelludo/patología , Neoplasias Vasculares/patología , Adulto JovenRESUMEN
ABSTRACT: An unusual benign skin tumor is reported occurring in a 68-year-old woman with no significant medical history. The lesion presented as a small skin nodule in the neck. Histologic examination showed a well-circumscribed superficial dermal nodule composed of a solid proliferation of large, round cells with abundant eosinophilic cytoplasm and small centrally placed nuclei displaying a vaguely chondroid appearance. Immunohistochemical studies showed strong positivity of the tumor cells for S100 protein and vimentin and negative staining for SOX10, melanoma cocktail, HMB45, Melan-A, cytokeratin AE1/AE3, inhibin, desmin, smooth muscle actin, CD68, CD164, and neuron specific enolase. Next-generation sequencing using a panel of 50 actionable genes commonly encountered in human neoplasia did not reveal the presence of any mutations. Owing to the remarkable similarity of the lesion to immature cartilage, we consider this to be a benign tumor, most likely resulting from an embryologic defect. We propose the term immature chondroid choristoma to designate this lesion.
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Coristoma/patología , Neoplasias Cutáneas/patología , Anciano , Femenino , Humanos , CuelloRESUMEN
Acral melanocytic neoplasms often pose diagnostic difficulty. Preferentially expressed antigen in melanoma (PRAME) expression and loss of p16 expression have diagnostic utility in melanocytic tumors. We examined PRAME and p16 expression in 30 acral melanocytic neoplasms (n = 11 nevi; n = 2 dysplastic nevi; n = 7 Spitz nevi; n = 10 acral melanomas). PRAME was scored as % positive nuclei: negative = 0%; 1% to 25% = 1+; 25% to 50% = 2+; 50% to 75% = 3+, or positive: 75% to 100% = 4+. p16 expression was defined as retained (homogeneous or checkerboard) or lost (complete or partial/regionally). PRAME expression was negative in all benign, dysplastic, and Spitz nevi. Conversely, all acral melanomas were diffusely (4+) positive for PRAME expression. p16 expression was retained in all benign acral nevi (8/11 homogeneous, 3/11 checkerboard), completely lost in one dysplastic nevus, and retained in all acral Spitz nevi (3/7 homogeneous, 4/7 checkerboard). p16 was retained in five of 10 acral melanomas (3/10 homogeneous; 2/10 checkerboard), and negative in five of 10 acral melanomas (absent in 3/10, partially lost in 2/10). Our data suggest that 4+ PRAME expression is highly sensitive and specific in the setting of acral melanomas and is a more predictive diagnostic tool compared with p16 immunohistochemistry.
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Antígenos de Neoplasias/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Melanoma/metabolismo , Nevo/metabolismo , Neoplasias Cutáneas/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Niño , Preescolar , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Nevo/patología , Neoplasias Cutáneas/patología , Adulto JovenRESUMEN
Nontuberculous mycobacteria are pathogens with diverse manifestations in immunocompromised hosts. The lesser-known Mycobacterium haemophilum usually causes cutaneous infection. Diagnosis is challenging but is aided by molecular testing and multidisciplinary communication. We present an immunocompromised patient with disseminated cutaneous mycobacterial infection with digital tenosynovitis.
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Trasplante de Células Madre Hematopoyéticas , Infecciones por Mycobacterium no Tuberculosas/patología , Complicaciones Posoperatorias/patología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
ABSTRACT: Cutaneous metastasis may be the initial sign of internal malignancy but more often represents a late manifestation of widely disseminated disease. Breast carcinoma is the most common malignancy to metastasize to the skin. Although several studies have detailed the histopathologic patterns of cutaneous metastasis from internal malignancies, very little has been published regarding metastases of breast carcinoma to the skin. Furthermore, the histopathologic and clinical features observed in the cases of breast carcinoma with local skin involvement as opposed to cases exhibiting distant cutaneous metastases have not been adequately investigated. We have reviewed 232 cases of breast carcinoma with cutaneous metastases from 2 large institutions. All cases of carcinoma of the breast with involvement of the skin of the anterior chest wall were compared with those with distant cutaneous metastases. Two hundred thirty-two cases in 199 patients were included, of which 126 had skin involvement exclusively involving the ipsilateral anterior chest, and 106 had biopsy-proven distant cutaneous metastases. Twelve patients had both local and distal spread. Distant cutaneous metastases showed a predilection for the contralateral anterior chest wall area, followed by the head and neck, back, and abdomen. Histologically, most of the tumors presented in this series showed features of infiltrating ductal carcinoma. In both ipsilateral and distant metastases, the tumors demonstrated little change in histologic features from the primary lesion; however, the distant metastases showed a tendency to display more poorly differentiated features. The mean patient survival when cutaneous involvement was localized to the skin of the anterior chest wall was 23 months as compared with 20.6 months when distant sites were affected. A comparison of the clinicopathologic features of the patients presented in this series suggests that alternate biological mechanisms may apply for local and distant skin metastases from breast carcinoma.
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Neoplasias de la Mama/patología , Carcinoma/secundario , Neoplasias Cutáneas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
CONTEXT.: Accurate diagnosis of melanocytic lesions is fundamental for appropriate clinical management. OBJECTIVE.: To evaluate the degree of discordance, if any, between histopathologic diagnoses of melanocytic lesions at referring institutions and at a tertiary referral cancer center and the potential impact of such discordance on clinical management. DESIGN.: We retrospectively identified all patients referred to our comprehensive cancer center for evaluation of a melanocytic lesion from January 2010 to January 2011. For each patient, the histopathologic diagnosis from the referring institution was compared with the histopathologic diagnosis from a dermatopathologist at our center. Discordances were classified as major if they resulted in a change in clinical management and minor if they did not. RESULTS.: A total of 1521 cases were included. The concordance rates were 72.2% (52 of 72) for dysplastic nevus, 75.0% (15 of 20) for all other types of nevi, 91.1% (143 of 157) for melanoma in situ, 96.1% (758 of 789) for invasive melanoma, and 99.6% (478 of 480) for metastatic melanoma. Major discordances were found in 20.2% of cases (307 of 1521), and minor discordances were found in 48.8% of cases (742 of 1521). Compared with the guideline-based treatment recommendation based on the referring-institution diagnosis, the guideline-based treatment recommendation based on the cancer center diagnosis was more extensive in 5.9% (89 of 1521) of patients and less extensive in 5.0% (76 of 1521) of patients. CONCLUSIONS.: Our findings underscore the importance of secondary histopathologic review of melanocytic lesions by expert dermatopathologists because significant changes in the diagnosis, tumor classification, and/or staging may be identified, thus, resulting in critical changes in recommendations for clinical management.
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Melanoma , Nevo , Neoplasias Cutáneas , Diagnóstico Diferencial , Humanos , Melanocitos , Melanoma/diagnóstico , Melanoma/terapia , Estudios Retrospectivos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapiaRESUMEN
Langerhans cell sarcoma (LCS) is rare and aggressive; patients have an overall survival rate of less than 50%. We present a 62-year-old man with a history of superficial spreading melanoma of the upper back with sentinel lymph node metastasis, Langerhans cell histiocytosis, and LCS. The patient presented with erythematous papules and scaly areas on his face, neck, arms, chest, abdomen, and legs. A skin biopsy revealed a proliferation of large neoplastic cells involving the dermis and with epidermotropism. These cells had atypical bean-shaped nuclei, with ample cytoplasm and abundant mitotic figures including atypical forms. Immunohistochemical studies showed the tumor to be diffusely positive for CD1a, S100 protein, and langerin (CD207) and negative for melanocytic markers. Some tumor cells were positive for cyclin D1. A diagnosis of LCS involving the skin was established. The present study is a very unusual case of LCS showing epidermotropism. The patient's history of metastatic melanoma posed additional challenges for diagnosis, underlying the need of immunophenotyping in these cases. Consensus for optimal standard therapy has not been established in LCS, and thus, early recognition is important since these neoplasms tend to recur and metastasize. LCS in skin is discussed and published cases are comprehensively reviewed.
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Sarcoma de Células de Langerhans/diagnóstico , Sarcoma de Células de Langerhans/metabolismo , Melanoma/diagnóstico , Piel/patología , Adolescente , Adulto , Cuidados Posteriores , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica/métodos , Lactante , Sarcoma de Células de Langerhans/tratamiento farmacológico , Masculino , Melanoma/patología , Persona de Mediana Edad , Recurrencia , Proteínas S100/metabolismo , Resultado del Tratamiento , Adulto JovenRESUMEN
Cutaneous carcinosarcomas are rare biphenotypic tumors that simultaneously show epithelial and mesenchymal differentiation. The most common carcinomatous components in skin carcinosarcomas are basal cell carcinoma and squamous cell carcinoma; adnexal carcinomas are rarely encountered. We report a case of an adnexal carcinoma with ductal and squamous differentiation and spindle cell component, which is interpreted as carcinosarcoma. Loss of immunohistochemical expression of E-cadherin and ß-catenin detected in the sarcomatous component suggested epithelial mesenchymal transition (EMT). RNA sequencing analysis identified several gene mutations and alterations such as translocations and upregulations/downregulations, either shared by the two components of the tumor or differentially present in the carcinoma or the sarcoma parts. Thus, mutations in genes, such as TP53, were found in both components of the tumor while mutations in PDGFRA and RB1 (a pathogenic missense mutation) were exclusively present in the sarcomatous areas, further supporting EMT. EMT is a dynamic process by which tumors acquire mesenchymal phenotype while simultaneously losing epithelial properties. Although the pathways involved in EMT have been extensively studied, this phenomenon still needs to be investigated in cutaneous tumors of adnexal origin for a better understanding of their pathogenesis. These molecular changes may represent promising targets for personalized therapies.
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Carcinosarcoma/diagnóstico , Transición Epitelial-Mesenquimal/genética , Neoplasias de Anexos y Apéndices de Piel/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Cadherinas/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/ultraestructura , Carcinosarcoma/genética , Carcinosarcoma/radioterapia , Carcinosarcoma/cirugía , Femenino , Genes p53/genética , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia/secundario , Análisis de Secuencia de ARN/métodos , Vimentina/metabolismoRESUMEN
Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade soft tissue neoplasm preferentially arising in the extremities of young to middle-aged adults characterized histologically by a variegated appearance and absence of a distinctive immunophenotype. Herein we have evaluated a series of 73 cases of MIFS to define potential features and markers that may facilitate diagnosis. An immunohistochemical study with a large panel of antibodies showed strong positivity of the tumor cells for bcl-1 (94.5%), FXIIIa (89%), CD10 (80%), and D2-40 (56%). FISH and array comparative genomic hybridization (aCGH) were performed in a large subset of cases to investigate the utility for detecting the TGFBR3 and OGA t(1;10) rearrangement and BRAF abnormalities. Using a combination of FISH and/or aCGH, t(1;10) was detected in only 3 of 54 cases (5.5%). The aCGH study also demonstrated amplification of VGLL3 on chromosome 3 that was detected in 8 of 20 cases (40%). BRAF alterations were observed by FISH in 4 of 70 cases (5.7%) and correlated with gain of chromosome 3p12 (VGLL3). A novel fusion transcript involving exon 6 of ZNF335 and exon 10 of BRAF was identified in one case. Demonstration of amplification of VGLL3 on chromosome 3 in combination with expression of bcl-1 and FXIIIa may help support the diagnosis, however, due to their low specificity these markers are not sufficient for a definitive diagnosis in the absence of the appropriate clinical-pathological context. Until a more robust genetic or immunohistochemical signature is identified, the diagnosis of MIFS rests on its characteristic clinicopathological features.