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Background/Objective: Allergic reactions to insulin have decreased significantly since the introduction of human insulin preparation, but up to 2.4% of insulin-treated patients can still be affected. Rituximab is a monoclonal antibody against the surface antigen CD20 on B lymphocytes, and it is largely used to treat lymphoproliferative and rheumatological conditions. In a very few published case reports, rituximab has been used as an investigational drug to treat severe insulin allergy refractory to conventional therapy. Here, we present an unusual case of a 40-year-old woman with T1DM and severe insulin allergy that was successfully treated with rituximab. Case Report: The patient was diagnosed with T1DM at age 37. Three years later, skin reactions developed at insulin administration sites. These consisted of pruritic and painful erythema and wheals that appeared within 1 to 4 h of insulin administration, followed by induration, subcutaneous nodules, and surrounding lipodystrophy that lasted several days with spontaneous resolution in 1 to 2 weeks. Extensive immunologic evaluation suggested the reaction was related to insulin allergy. Skin biopsy revealed sublobular panniculitis. After failed conventional treatment with antihistamines, glucocorticoid, and various insulins, rituximab infusion as an investigational approach was initiated. This was very successful, leading to prolonged remission of her insulin allergy. Discussion: First-line management of insulin allergy should focus on second-generation antihistamines and switching insulin preparation. In refractory cases, systemic immunotherapy with rituximab can be a viable option. Conclusion: Practitioners should be aware that in patients with insulin allergy who fail conventional treatment, immunotherapy with rituximab can be a viable option.
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¼ Negative margin resection of musculoskeletal sarcomas is associated with reduced risk of local recurrence.¼ There is limited evidence to support an absolute margin width of soft tissue or bone that correlates with reduced risk of local recurrence.¼ Factors intrinsic to the tumor, including histologic subtype, grade, growth pattern and neurovascular involvement impact margin status and local recurrence, and should be considered when evaluating a patient's individual risk after positive margins.¼ Appropriate use of adjuvant therapy, critical analysis of preoperative advanced cross-sectional imaging, and the involvement of a multidisciplinary team are essential to obtain negative margins when resecting sarcomas.
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Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Márgenes de Escisión , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Proliferación Celular , Terapia CombinadaAsunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Trasplante Autólogo , Persona de Mediana Edad , FemeninoRESUMEN
Merkel cell carcinoma (MCC) is a rare neoplasm that arises in the skin of elderly patients on sun-exposed areas such as the head, neck, and extremities. Involvement of the epidermis by tumor cells is a relatively uncommon phenomenon. However, a few cases have been reported of Merkel cell carcinoma in situ (MCCIS) in which tumor cells are confined exclusively to the epidermis without dermal involvement. Herein, we present a peculiar MCCIS lesion in a 66-year-old man composed of tumor cells in a nested and lentiginous growth pattern, exhibiting variable quantities of intracytoplasmic dusty brown pigment consistent with melanin, thus closely mimicking melanoma in situ. In addition, the lesion was associated with invasive squamous cell carcinoma, which has not been previously reported in the literature. An extensive search of the PubMed-indexed, English-language literature yielded only 17 case reports of MCCIS without documented invasion in which clinical data were available. Out of the cases with available clinical information, individuals with strict MCCIS (n = 13) showed no evidence of recurrence or metastases. The median follow-up time in the cases with available data (n = 9) was 12 months (mean 12.8 months, range 6-21). Thus, MCCIS without invasion may have a favorable clinical course in contrast to invasive MCC tumors.
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Carcinoma de Células de Merkel , Carcinoma de Células Escamosas , Melanoma , Neoplasias Cutáneas , Masculino , Humanos , Anciano , Carcinoma de Células de Merkel/diagnóstico , Carcinoma de Células de Merkel/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Melanoma/diagnóstico , Carcinoma de Células Escamosas/patología , Melanoma Cutáneo MalignoRESUMEN
Anastomosing hemangiomas (AH) are rare benign masses. We report an occurrence of AH in the breast during pregnancy, its pathological analysis, and clinical management. Key in the evaluation of these rare vascular lesions is differentiating AH from angiosarcoma. A low proliferative Ki-67 index and small size on imaging and final pathology will confirm AH from angiosarcoma. Clinical management of AH requires surgical resection and standard interval mammography and clinical breast examination.
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Hemangioma , Hemangiosarcoma , Humanos , Embarazo , Femenino , Hemangiosarcoma/diagnóstico , Hemangioma/diagnóstico por imagen , Hemangioma/cirugía , MamografíaRESUMEN
Uterine mesenchymal lesions demonstrate various underlying genomic alterations involving MED12 , JAZF1 , YWHAE , BCOR , and ALK genes, among others. Recent publications describe a subset of high-grade endometrial stromal sarcoma lesions harboring BCORL1 gene aberrations including JAZF1::BCORL1 . Herein, we present an unusual benign endomyometrial spindle cell lesion that defies classificatory efforts by demonstrating mixed histomorphologic and immunohistochemical features of endometrial stromal nodule, leiomyoma, and uterine inflammatory myofibroblastic tumor while harboring a JAZF1::BCORL1 . The lesion was found in a 43-yr-old woman with pelvic pain and heavy menses as a 5.5 cm well-circumscribed ulcerated mass fungating from the cervical os. Microscopic examination revealed a polypoid, well-circumscribed, moderately cellular endomyometrial tumor composed by bland spindle cells haphazardly disposed within a slightly edematous stroma enriched by a delicate network of thin-walled vessels that were occasionally encircled by the tumor cells. Unequivocal evidence of tongue-like growth pattern into the myometrium, tumor-type necrosis or increased mitotic activity was not identified after sampling the entire lesion. The lesion showed patchy immunoreactivity for both smooth muscle actin-alpha and desmin while negative for CD10, HMB45, ALK (D5F3), and BCOR. An Archer FusionPlex panel assay demonstrated a fusion involving both exons 4 from the JAZF1 and BCORL1 genes. The JAZF1::BCORL1 has not, to the best of our knowledge, been previously reported in a benign/low-grade mesenchymal uterine lesion.
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Neoplasias Endometriales , Lesiones Precancerosas , Sarcoma Estromático Endometrial , Neoplasias Uterinas , Femenino , Humanos , Neoplasias Endometriales/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Factores de Transcripción/genética , Sarcoma Estromático Endometrial/patología , Proteínas Tirosina Quinasas Receptoras , Proteínas de Unión al ADN , Proteínas Co-Represoras/genética , Proteínas Represoras/genéticaRESUMEN
A 74-year-old man with a medical history significant for papillary thyroid cancer (PTC) presented with a rapidly enlarging grape-sized mass in his right medial arm with paresthesia in the ulnar nerve distribution. Imaging was suspicious for a peripheral nerve sheath tumor (PNST), but an ultrasound-guided biopsy was equivocal. The mass was excised with final histopathology demonstrating a benign neurofibroma/schwannoma hybrid nerve sheath tumor (N/S HNST) harboring a metastatic PTC deposit, ultimately mimicking the rare glandular schwannoma subtype. Next-generation sequencing (NGS) of the lesion demonstrated somatic variants in BRAF and TERT (common in PTC) and NF2 (common in PNSTs). After excision, the patient's nerve symptoms improved. A postsurgical PET/CT scan also showed progression in the lungs/mediastinum. Due to the metastatic nature of his PTC, he was treated with 14 mg of Lenvima (lenvatinib) daily, and his PET/CT surveillance was performed at more frequent intervals. Tumor-to-tumor metastasis (TTM) is a rare occurrence. To our knowledge, this is the first case reported on PTC metastasizing into a benign (hybrid) PNST, which mimicked glandular schwannoma. Symptomatology, imaging characteristics, NGS, and histopathological characteristics that can decipher between different benign PNST subtypes (schwannoma, neurofibroma, glandular, hybrid, etc.), malignant PNSTs (MPNSTs), and TTM are described.
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Breast implant augmentation is a low-risk procedure with few life-threatening complications. Capsular contracture and rupture/leakage of the implant are the most common complications encountered. Malignant breast implant augmentation-associated lesions are rare, with anaplastic large cell lymphoma being the most common. Squamous cell carcinomas associated with breast implant augmentation are exceedingly rare, with only eight patients reported. Breast implant capsule-associated squamous cell carcinoma occurs in patients with long standing breast implant augmentations (>11 years). We report two additional patients with breast implant capsule-associated squamous cell carcinoma. Review of the literature reveals that invasion beyond the breast implant capsule into the adjacent tissue by the squamous cell carcinoma appears to have negative prognostic implications, and possibly warrants close clinical follow-up.
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Implantación de Mama , Implantes de Mama , Neoplasias de la Mama , Carcinoma de Células Escamosas , Linfoma Anaplásico de Células Grandes , Mamoplastia , Humanos , Femenino , Implantes de Mama/efectos adversos , Implantación de Mama/efectos adversos , Mamoplastia/efectos adversos , Linfoma Anaplásico de Células Grandes/etiología , Neoplasias de la Mama/patología , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/cirugíaRESUMEN
Penile intraepithelial neoplasia (PeIN) is classified as human papillomavirus (HPV)- and non-HPV-related. This classification is associated with distinct morphologic subtypes. The natural history and prognosis of PeIN subtypes are not well known. This study aims to evaluate clinicopathological features, HPV status, and outcome of PeIN subtypes. Eighty-two lesions from 64 patients with isolated PeIN were retrospectively reviewed. Mean age was 59 years. Lesions were multicentric in 34% of patients and affected glans (33%), shaft (26%), and foreskin (20%). Histologically, 22% of patients had coexisting lesions, classified as hybrid and mixed. HPV-related PeIN (97%) included basaloid (59%), warty (8%), warty-basaloid (8%), hybrid (19%) and mixed (3%) types. P16 and HPV positivity occurred in 99% and 82% of lesions, respectively. HPV 16 was more common in basaloid PeIN. Multiple genotypes were detected in 35%, more commonly in hybrid PeIN (P = 0.051). Positive margins occurred in 63% of excisions. PeIN recurred in 48% of excisions and 30% of overall repeated procedures, and progression to invasive carcinoma occurred in 2%. At follow-up, 86% of patients had no evidence of disease and 12% were alive with disease. Lichen sclerosus occurred in non-HPV and HPV-related PeIN (100% and 47%).In conclusion, HPV-related and, more specifically basaloid PeIN were the predominant types and preferentially associated with HPV 16. While PeIN had a high recurrence rate, there was a slow and infrequent progression to invasive or metastatic carcinoma with multimodal treatments. Additional studies are needed to understand biology and natural history of PeIN.
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Alphapapillomavirus , Carcinoma in Situ , Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Neoplasias del Pene , Neoplasias Cutáneas , Lesiones Intraepiteliales Escamosas , Carcinoma in Situ/patología , Carcinoma in Situ/terapia , Carcinoma de Células Escamosas/patología , Humanos , Masculino , Persona de Mediana Edad , América del Norte , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/patología , Neoplasias del Pene/patología , Neoplasias del Pene/terapia , Estudios RetrospectivosRESUMEN
BACKGROUND: Human epidermal growth factor 2 (HER2) amplification and/or overexpression occurs in 12% to 25% of breast cancers. Accurate detection of HER2 is critical in predicting response to HER2-targeted therapy. Both immunohistochemistry (IHC) and in situ hybridization (ISH) are FDA-approved methods for detecting HER2 status because its protein overexpression is largely attributable to gene amplification. However, variable discordant results between IHC and ISH have been reported. METHODS: We determined the frequency of HER2 IHC/ISH discordance in these patients and also performed a pooled literature review analysis. RESULTS: Of the 1125 consecutive primary or metastatic breast cancers with HER2 IHC and ISH performed simultaneously between 2015 and 2020, 84.6% had an unequivocal HER2 status. Discordance was found in 30 cases from 26 patients, including 13 IHC-/ISH+ and 17 IHC+/ISH-, representing 1.6% and 11.9% of IHC- and IHC+ cases, respectively. Review of the literature between 2001 and 2020 identified 46 relevant studies, with a total of 43,468 cases with IHC and ISH performed. The IHC-/ISH+ and IHC+/ISH- discordances were seen in all antibody clones and ISH methods used. The IHC+/ISH- discordance was significantly higher than IHC-/ISH+ (13.8% vs. 3%, P < .0001). The overall discordance constituted 4% of all cases and 5.4% of those with an unequivocal IHC status. Significantly lower incongruities for both IHC-/ISH+ and IHC+/ISH- were found in those published after 2018. The discordances probably reflect altered biology of HER2 oncogene/oncoprotein. Routinely performing both IHC and ISH may uncover such cases to prevent denial of potentially beneficial targeted therapy.
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Neoplasias de la Mama/metabolismo , Inmunohistoquímica/normas , Hibridación in Situ/normas , Receptor ErbB-2/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Errores Diagnósticos , Femenino , Amplificación de Genes , Humanos , Hibridación Fluorescente in Situ/métodos , Variaciones Dependientes del ObservadorRESUMEN
Myoepithelial tumors arising in soft tissue are uncommon and mostly manifest a benign clinical course, although a malignant form does exist. An EWSR1 gene rearrangement is a common event in these tumors. Ossifying fibromyxoid tumor, a rare soft tissue neoplasm of uncertain differentiation, may have overlapping histologic and immunophenotypic features with myoepithelial tumors, but frequently harbors a PHF1 gene rearrangement. Interestingly, a PHF1-TFE3 fusion has been recently reported in both entities. Here we report a case of a malignant soft tissue tumor demonstrating myoepithelial differentiation and harboring a PHF1-TFE3 fusion. Despite being slow-growing and lacking significant cytologic atypia at initial presentation, the patient deteriorated rapidly with local recurrence and distant metastases. A discussion of the potential clinicopathologic implications of a PHF1-TFE3 fusion in these entities is also developed.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Proteínas de Unión al ADN/genética , Fibroma Osificante/genética , Mioepitelioma/genética , Fusión de Oncogenes , Proteínas del Grupo Polycomb/genética , Neoplasias de los Tejidos Blandos/genética , Femenino , Fibroma Osificante/patología , Reordenamiento Génico , Humanos , Persona de Mediana Edad , Mioepitelioma/patología , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
Spindle cell squamous cell carcinoma (SpC-SCC) is rare, accounting for 0.4-4% of head and neck (HN) SCCs. Better understanding of HN SpC-SCC clinicopathologic characteristics, especially features that predict outcome, is needed. We present a clinicopathologic review of 71 HN mucosal SpC-SCC from three tertiary centers. The patient population showed a median age of 63 years (range 20-91), slight male predominance (M:F = 1.6:1), and a preponderance of smokers/ex-smokers (45/71, 64%). Most lesions involved oral cavity (42/71, 59%), especially oral tongue (n = 18), and larynx (n = 20, 28%). Polypoid/exophytic growth and surface ulceration were seen in 60% and 86% of cases, respectively. Histologically, most tumors showed sarcoma-like pattern (65/70, 93%), the remaining exhibiting granulation tissue-like or fibromatosis-like patterns, and 5 lesions showed osteosarcomatous/chondrosarcomatous elements. Most tumors (53/71, 74%) showed a conventional SCC (C-SCC) component, keratinizing (86%) or non-keratinizing/basaloid (14%). Nodal metastases, seen in 22 (31%) of resection specimens, showed SpC-SCC and/or C-SCC histomorphology. By immunohistochemistry, 76% of lesions showed immunoreactivity for keratin and 62/60% of lesions were p40/p63 positive. Ki-67 proliferation index ranged from 5 to 70%. Follow-up was available on 69 patients, median of 1.1 years from the time of SpC-SCC diagnosis. The 3-, 5-, and 10-year disease-specific survival (DSS) was 62, 37, and 12%, respectively. AJCC pN stage was an independent prognostic factor for DSS and distant metastasis-free survival (DMFS), whereas the presence of C-SCC was independently associated with improved DMFS. HN SpC-SCC is rare and might be diagnostically challenging. AJCC pN stage and co-existing C-SCC component appear to be prognostically relevant.
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Sarcoma/diagnóstico , Sarcoma/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Diagnóstico Diferencial , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Adnexal skin tumors are diagnostically challenging with few known molecular signatures. Recently, however, YAP1-MAML2 and YAP1-NUTM1 fusions were identified in poroid adnexal skin tumors. METHODS: Herein, we subjected eight poroid adnexal skin tumors (three poromas and five porocarcinomas) to fusion gene analysis by whole transcriptome sequencing and next-generation DNA sequencing analysis. RESULTS: YAP1 fusions were identified in six cases. YAP1-NUTM1 fusions were identified in two poromas and three porocarcinomas. A single case of porocarcinoma harbored a YAP1-MAML2 fusion. Two cases were negative for gene fusion. All cases that harbored YAP1-NUTM1 fusions showed nuclear protein in testis (NUT) expression by immunohistochemistry, with NUT being negative in the YAP1-MAML2-positive case. In this case series, we provide a detailed histopathologic description of six YAP1-fused poroid skin tumors, which we show harbor reproducible histopathologic features, to include broad, bulbous tumor tongues with admixtures of basaloid, poroid cells punctuated by squamatized cuticles and ductules, with uniform tumor nuclei featuring frequent grooves and pseudonuclear inclusions. CONCLUSIONS: Awareness of the characteristic histopathologic features of YAP1-fused poroid adnexal skin tumor is a step toward a more reproducible classification of adnexal skin tumors as well as a step toward targeted therapy for metastatic and/or unresectable examples of this poroid group of neoplasms.
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Porocarcinoma Ecrino/genética , Fusión Génica/genética , Reordenamiento Génico/genética , Poroma/genética , Anciano , Anciano de 80 o más Años , Concienciación , Porocarcinoma Ecrino/diagnóstico , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias , Proteínas Nucleares , Patología Molecular/métodos , Poroma/diagnóstico , Neoplasias Cutáneas/patología , Neoplasias de las Glándulas Sudoríparas/patología , Transactivadores , Secuenciación del Exoma/métodos , Proteínas Señalizadoras YAPRESUMEN
Clear cell hidradenoma (CCH) is an uncommon adnexal tumor usually arising from eccrine glands and commonly seen on the face and the upper extremities. CCH occurring in the breast is extremely rare. Herein we report a case of MAML2-rearranged CCH of breast with a papillary architecture closely mimicking intraductal papilloma, adenomyoepithelioma and low-grade mucoepidermoid carcinoma, thus representing a source of diagnostic confusion. An overview of salient histologic features and immunophenotypes to distinguish CCH and low-grade mucoepidermoid carcinoma is also integrated into the report.
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Neoplasias de la Mama/patología , Carcinoma Mucoepidermoide/patología , Predisposición Genética a la Enfermedad/genética , Transactivadores/metabolismo , Translocación Genética/genética , Acrospiroma/diagnóstico , Acrospiroma/genética , Acrospiroma/patología , Biomarcadores de Tumor/genética , Mama/patología , Neoplasias de la Mama/genética , Carcinoma Mucoepidermoide/diagnóstico , Femenino , Reordenamiento Génico/genética , Humanos , Transactivadores/genética , Factores de Transcripción/genética , Adulto JovenRESUMEN
Angiomyolipomas (AMLs) are triphasic tumors (smooth muscle, vascular and adipocytic components) with myomelanocytic differentiation, arising most commonly in the kidneys, which can show predominant epithelioid morphology and fat-predominant or fat-poor variants. Fat-predominant AMLs can show areas of hypercellularity and lipoblast-like cells, and these features can mimic well-differentiated liposarcoma (WDLS). To date, only one documented metastatic epithelioid AML showed unequivocal MDM2 amplification by fluorescence in situ hybridization. We describe our findings in a series of 35 AMLs including epithelioid, fat-poor, and fat-predominant variants, following interrogation of the MDM2 locus by FISH and CISH assays. MDM2 amplification was detected in 1 fat-predominant AML. Our findings demonstrate that rare MDM2 amplifications can occur in AMLs. We favor that this finding likely represents a "molecular bystander" event since these tumors are mainly driven by aberrations in the TSC1/TSC2 genes. Nevertheless, the presence of MDM2 amplification in a fat-predominant AML could present a potential diagnostic pitfall, particularly when confronted with the differential diagnosis of fat-predominant AML and WDLS in limited material from the retroperitoneum.
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Tejido Adiposo/patología , Angiomiolipoma/genética , Biomarcadores de Tumor/genética , Amplificación de Genes , Neoplasias Renales/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Adulto , Anciano , Anciano de 80 o más Años , Angiomiolipoma/patología , Diagnóstico Diferencial , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hibridación Fluorescente in Situ , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las PruebasRESUMEN
Cutaneous adnexal malignancies are biologically and pathologically diverse, and associated with a range of clinical outcomes. Given their rarity, the prognosis and optimal treatment of these neoplasms remains unclear. A single institution database from a tertiary care cancer center of patients treated for malignant cutaneous adnexal tumors was retrospectively analyzed. Clinicopathologic variables and outcome measures were analyzed in patients undergoing wide excision with or without sentinel node biopsy. 103 patients were analyzed; the majority of tumors were of eccrine sweat gland derivation (n = 69, 70%), and these exhibited a higher rate of nodal involvement and overall worse outcome. Sixteen patients (16%) demonstrated nodal metastasis, which included 10 (10%) with nodal disease at presentation and 6 who developed nodal metastasis during followup. 20 patients underwent sentinel node biopsy, and 2 (10%) had a positive sentinel node. 62% of nodal metastases occurred in patients with porocarcinoma. Seven patients died of disease (7%) with a median time from diagnosis to death of 48 months (range, 10-174). After a median follow up of 44.7 months, age > 70 years and larger tumor size were significantly associated with worse overall survival. Adnexal malignancies are rare tumors, and there is a paucity of information to guide the clinician in determining optimum surgical and medical treatment. Tumors of eccrine derivation, especially porocarcinomas, have a high risk of nodal involvement and may be considered for sentinel node biopsy.
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Neoplasias de Anexos y Apéndices de Piel/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Anexos y Apéndices de Piel/mortalidad , Neoplasias de Anexos y Apéndices de Piel/terapia , Estudios Retrospectivos , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Adulto JovenRESUMEN
Prostate cancer is well known to metastasize to the testis and is not an uncommon finding on castration performed for advanced disease. Although germ cell tumors make up the majority of testis neoplasms, there are more rare tumors, such as rete testis adenocarcinoma, that can mimic metastatic disease. NKX3.1 and prostein (P501S) are antibodies highly specific for prostate origin. Relatively little is known of the expression of these markers in testicular tissue. We investigated the expression of NKX3.1 and P501S in testicular tissues, sex cord-stromal tumors, germ cell tumors, and rete testis adenocarcinoma. We found strong diffuse nuclear staining for NKX3.1 in Sertoli cells of the testis. Expression of NKX3.1 was seen in 0/3 ovarian Sertoli cell tumors, 1/4 testicular Sertoli cell tumors, and in the Sertoli cell component of 1/12 ovarian Sertoli-Leydig cell tumors. We found moderate, diffuse cytoplasmic positivity for P501S in rete testis epithelium and in testicular Leydig cells. P501S also highlighted Leydig cells in 9/12 Sertoli-Leydig cell tumors of the ovary. Two of 3 Leydig cell tumors of the testis showed weak to moderate, diffuse cytoplasmic staining for P501S. All cases of embryonal carcinoma and pure seminoma were negative for both NKX3.1 and P501S. One case of rete testis adenocarcinoma showed patchy positivity for both NKX3.1 and P501S. In conclusion, NKX3.1 shows routine expression in Sertoli cells and P501S shows routine expression in Leydig cells and rete testis epithelium. In addition, these markers can be positive in sex cord-stromal tumors and rete testis adenocarcinoma.
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Adenocarcinoma/metabolismo , Biomarcadores de Tumor/biosíntesis , Proteínas de Homeodominio/biosíntesis , Proteínas de la Membrana/biosíntesis , Neoplasias Ováricas/metabolismo , Tumores de los Cordones Sexuales y Estroma de las Gónadas/metabolismo , Neoplasias Testiculares/metabolismo , Factores de Transcripción/biosíntesis , Anciano de 80 o más Años , Femenino , Humanos , MasculinoRESUMEN
GLI1 fusions involving ACTB, MALAT1, and PTCH1 genes have been recently reported in a subset of malignant soft tissue tumors with characteristic monomorphic nested epithelioid morphology and frequent S100 positivity. However, we encountered a group of morphologically similar soft tissue tumors lacking the canonical GLI1 gene fusions and sought to investigate their genetic abnormalities. A combined approach including RNA sequencing, targeted exome sequencing and FISH methodologies were used to identify potential novel genetic abnormalities. Ten patients (five females, five males) with an age range of 4-65 years (median 32.5) were identified. Tumors were located in the soft tissues of the limbs, trunk and head and neck, with one each in the tongue and lung. Histologically, tumors revealed ovoid to epithelioid cells arranged in a distinctive nested-trabecular pattern, separated by thin septa and a delicate vascular network. Two cases showed areas of increased nuclear pleomorphism and focal fascicular spindle cell growth. Four tumors showed a high mitotic count (≥15/10 HPFs), with necrosis seen in three of them. Lymphovascular invasion was noted in two cases. No consistent immunoprofile was detected, with positivity for CD56 (six cases), S100 (four cases), SMA (two cases), and pan-CK (one case). FISH showed GLI1 (12q13.3) gene amplification in all 10 cases, with co-amplification of CDK4 (12q14.1) in nine (90%) and MDM2 (12q15) in eight (80%) cases. Targeted exome sequencing performed in three cases confirmed the GLI1, CDK4, and MDM2 co-amplification. Only one case showed the presence of both GLI1 break-apart and amplification, although no gene partner was detected. Our findings suggest that GLI1 amplification, often associated with co-amplifications of CDK4 and MDM2 genes, may represent an alternative genetic mechanism of GLI1 oncogenic activation akin to GLI1 fusions, defining the pathogenesis of an emerging group of malignant soft tissue tumors with a distinctive nested growth pattern and variable immunoprofile.