RESUMEN
A distinctive histological variant of poorly differentiated, sarcomatoid, non-small cell lung carcinoma characterized by a discohesive population of giant tumor cells associated with prominent interstitial inflammatory cell infiltrates is described. The tumors occurred in 7 women and 7 men, 42 to 72 years of age (mean: 56 y). They predominantly affected the upper lobes and measured 1.3 to 9 cm in greatest diameter (mean: 4.6 cm). The tumor cells were characterized by large pleomorphic nuclei with prominent nucleoli, ample cytoplasm, and frequent abnormal mitoses, and were surrounded by a dense inflammatory cell infiltrate, often associated with emperipolesis. Immunohistochemical stains were positive in the tumor cells for cytokeratin AE1/AE3 and CK8/18 and negative for TTF1, napsin A, p40, and CK5/6. Next-generation sequencing was performed in all cases using the Oncomine Precision Assay; the most common abnormalities found included TP53 mutations (9 cases) and AKT1 amplification (8 cases), followed by KRAS mutations (4 cases) and MAP2K1/2 mutations (4 cases). Clinical follow-up was available in 13 patients. Three patients presented with metastases as the initial manifestation of disease; 8 patients died of their tumors from 6 months to 8 years (mean: 2.7 y); 3 patients were alive and well from 4 to 6 years; and 2 patients had metastases when last seen but were lost to follow-up thereafter. The importance of recognizing this distinctive and aggressive variant of non-small cell lung carcinoma lies in avoiding confusion with a sarcoma or other types of malignancy.
RESUMEN
Non-small cell lung carcinoma with predominantly clear cell features is a rare histologic presentation of lung carcinoma. We have examined 31 cases of lung carcinomas showing extensive clear cell features. The patients were 10 women and 21 men aged 47-92 years (mean: 70 years). The tumors showed a predilection for the right upper and lower lobes and measured from 0.8 to 9.5 cm (mean: 4.2 cm). By immunohistochemistry, 9 cases were typed as adenocarcinoma, 19 cases as squamous cell carcinoma, and 3 showed a "null" phenotype with complete loss of markers for adenocarcinoma or squamous cell carcinoma. Most cases that typed as adenocarcinoma showed a solid growth pattern. A subset of the solid adenocarcinoma cases showed a distinctive "pseudosquamous" morphology. Next-generation sequencing was performed in 20 cases and showed a variety of molecular alterations. The most common abnormalities were found in the TP53 gene (9 cases), FGFR gene family (8 cases), KRAS (5 cases), AKT1 (5 cases), and BRAF (3 cases). Clinical follow-up was available in 21 patients; 16/21 patients died of their tumors from 6 months to 12 years after initial diagnosis (mean: 4.2 years, median: 1.5 years). Four patients were alive and well from 4 to 27 years (mean: 11.5 years, median: 7.5 years); all were pathologic stage 1 or 2. NSCLC with clear cell features can display aggressive behavior and needs to be distinguished from various other tumors of the lung that can show clear cell morphology. The identification of targetable molecular alterations in some of these tumors may be of value for therapeutic management.
Asunto(s)
Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas , Inmunohistoquímica , Neoplasias Pulmonares , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Mutación , Secuenciación de Nucleótidos de Alto Rendimiento , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/genéticaRESUMEN
The diagnosis of low-grade fibroblastic/myofibroblastic tumors of acral sites can be challenging. These tumors encompass a diverse group of neoplasms with a spectrum of biologic potential ranges from benign to overtly malignant. They often demonstrate significant clinical, radiologic, and immunophenotypic overlap, in which the molecular phenotype may play an important diagnostic role to arrive at the final diagnosis. Herein, we report a case of soft tissue mass lesion presented on the palm of an adult patient for four months. Histologically, the tumor consisted of primarily low-grade spindle cells expressing smooth muscle actin. Molecular testing revealed a novel SREBF1::USP6 fusion gene, confirming the final diagnosis of nodular fasciitis and ultimately expanding its molecular profile. This case highlights the diagnostic value of single, cost-effective, targeted molecular panel to arrive at an accurate diagnosis and provide helpful therapeutic information.
Asunto(s)
Proteína 2 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Ubiquitina Tiolesterasa , Humanos , Ubiquitina Tiolesterasa/genética , Proteínas Similares a la Angiopoyetina/genética , Proteínas Similares a la Angiopoyetina/metabolismo , Fibromatosis Agresiva/patología , Fibromatosis Agresiva/genética , Femenino , Masculino , Angiopoyetinas/genéticaRESUMEN
Seven cases of primary lung tumors characterized histologically by clear cell morphology and a distinctive FGFR3::TACC3 gene rearrangement are described. The tumors arose in 4 women and 3 men, aged 47 to 81 years (mean=68). They occurred in peripheral locations, predominantly subpleural, and ranged in size from 1.4 to 6.5 cm (mean=4.1 cm). All tumors showed a solid growth pattern with abundant central areas of necrosis and marked nuclear pleomorphism. The tumors demonstrated clear cell histology, with large cohesive tumor cells displaying atypical nuclei and abundant clear cytoplasm. Immunohistochemical stains identified a squamous phenotype in 5 cases and an adenocarcinoma phenotype in 2 cases. One case was a squamous cell carcinoma with focal glandular component, and one of the squamous cell carcinomas showed focal sarcomatoid changes. Next generation sequencing identified FGFR3::TACC3 gene rearrangements in all 7 cases. One case demonstrated a concurrent activating FGFR3 mutation and a second case demonstrated concurrent FGFR3 amplification. Two cases harbored a concurrent KRAS G12D mutation. One case harbored both KRAS and EGFR mutations, and 1 case had a concurrent TP53 mutation. Non-small cell lung carcinoma harboring FGFR3::TACC3 gene rearrangements is extremely rare, and this rearrangement may potentially be enriched in tumors that demonstrate clear cell histology. Identification of FGFR3::TACC3 in patients with lung carcinomas with clear cell features may be of importance as they could potentially be candidates for therapy with tyrosine kinase inhibitors.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Masculino , Humanos , Femenino , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas de Fusión Oncogénica/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Carcinoma de Células Escamosas/patología , Mutación , Aberraciones Cromosómicas , Proteínas de Ciclo Celular/genética , Reordenamiento Génico , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/metabolismo , Proteínas Asociadas a Microtúbulos/genéticaRESUMEN
Periosteal fasciitis is a subtype of nodular fasciitis originating from the periosteum. The diagnosis can be challenging and requires radiologic-pathologic correlation. Advances in molecular analysis confirmed that nodular fasciitis and its related lesions harbor a USP6 gene rearrangement with one of the several potential partners. Herein, we report a case of periosteal fasciitis with metaplastic bone formation detected incidentally during a radiologic survey for breast carcinoma. Radiologic examination revealed a 2.4 cm, heterogeneous, avidly enhancing lesion of the right femoral distal metaphysis concerning for low-grade periosteal chondrosarcoma. Histological examination of a core needle biopsy revealed a tumor composed of bland spindle cells with myofibroblastic and osteoblastic phenotypes admixed with immature bone and cartilaginous elements. Molecular analysis revealed a novel STAG1::USP6 fusion that helped arrive at the right diagnosis and further expands the molecular profile of USP6-associated neoplasms.
Asunto(s)
Neoplasias Óseas , Fascitis , Fibroma , Humanos , Proteínas Proto-Oncogénicas/genética , Reordenamiento Génico , Ubiquitina Tiolesterasa/genética , Fascitis/diagnóstico por imagen , Fascitis/genética , Fibroma/genética , Neoplasias Óseas/genética , Proteínas Nucleares/genéticaRESUMEN
MEIS1::NCOA1/2 sarcomas are a newly recognized group of exceedingly rare low-grade spindle cell sarcomas that often involve the genitourinary and gynecologic tracts. Due to its deceptively low-grade morphology and the non-specific immunoprofile, these neoplasms may pose a diagnostic challenge by histologically mimicking other entities such as endometrial stromal sarcoma, smooth muscle tumor, or uterine perivascular epithelioid cell tumor (PEComa). Histologically, MEIS1::NCOA1/2 sarcomas typically show spindle cell proliferation with hyperchromatic nuclei and a generalized cytologic uniformity, arranged in short fascicles and exhibiting alternating zones of hypo- and hypercellularity. Among the previously reported cases, molecular analysis revealed the MEIS1::NCOA2 fusion as the most commonly detected fusion gene, whereas the MEIS1::NCOA1 fusion gene has been reported in only a single case that involved kidney. Herein we report the first case of uterine sarcoma harboring the MEIS1::NCOA1 fusion gene that was initially misclassified as low-grade endometrial stromal sarcoma, demonstrating its clinicopathologic features, and highlighting the essential role of molecular pathology to arrive at the accurate diagnosis that may alter disease classification and inform therapy.
Asunto(s)
Neoplasias Endometriales , Sarcoma Estromático Endometrial , Neoplasias Uterinas , Humanos , Femenino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Sarcoma Estromático Endometrial/diagnóstico , Sarcoma Estromático Endometrial/genética , Sarcoma Estromático Endometrial/patología , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Útero/patología , Coactivador 1 de Receptor Nuclear/genéticaRESUMEN
Solitary fibrous tumors (SFTs) are ubiquitous soft tissue neoplasms known for their protean histology and potentially aggressive behavior. Although most cases are composed of a monotonous proliferation of spindle cells, some tumors show unusual cytologic features. We have studied 13 SFTs that were characterized by a predominant population of round epithelioid cells with abundant eosinophilic cytoplasm and clear cell changes. The tumors occurred in 8 women and 5 men, aged 36 to 80 years (mean=63 y), and were located within the orbit (3), lower extremity (3), retroperitoneum (2), abdominal cavity (2), and superficial soft tissues of the neck, pelvis, and pubis (1 each). The tumors measured from 3.5 to 24.5 cm. Using a risk assessment system, 6 cases were stratified as low-risk tumors; 3 of these showed no evidence of recurrence or metastases from 6 to 18 years, and 1 tumor in the orbit recurred and led to the patient's demise. Five cases were of intermediate risk; clinical follow-up showed no evidence of recurrence or metastases from 3 to 4 years in 3 patients, and 1 patient suffered a recurrence 4 years after diagnosis. Two cases were high risk; 1 patient died after 1 year and the second patient experienced local recurrence at 4 years. Immunohistochemical studies showed nuclear positivity for STAT6 in 10 cases. CD34 immunohistochemistry was positive in 11 cases. A NAB2::STAT6 rearrangement was present in all cases. Epithelioid and clear cell SFT should be considered in the differential diagnosis of soft tissue neoplasms with epithelioid and clear cell morphology.
Asunto(s)
Neoplasias de los Tejidos Blandos , Tumores Fibrosos Solitarios , Femenino , Humanos , Masculino , Biomarcadores de Tumor/genética , Biología Molecular , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Tumores Fibrosos Solitarios/genética , Tumores Fibrosos Solitarios/patología , Factor de Transcripción STAT6/genética , Antígenos CD34/genéticaRESUMEN
Acral lentiginous melanoma (ALM) is a rare type of cutaneous melanoma with a poor prognosis. It is unclear whether the poor outcome of ALM is due to its inherent disease characteristics or advanced stage at initial diagnosis. To address this question, we retrospectively analyzed the clinicopathologic factors of 828 thin (T1; Breslow thickness ≤1.0 mm) melanomas [129 (15.6%) ALMs and 699 (84.4%) non-ALMs] and their nodal and distance metastases and local recurrence rates and determined their relationship with the disease-specific (DSS), overall (OS), and recurrence-free survivals (RFS) at the pathologic stages T1, T1a, and T1b with a median follow-up time of 84.5 months. With the exception of OS at T1b stage, ALM patients showed significantly lower 5- and 10-year DSS, OS, and RFS rates at every pathologic stage when compared with non-ALM. In multivariable analysis, ALM histologic type, SLN positivity, age, and the use of systemic therapy were detected as independent poor prognostic factors associated with significantly lower survival rates. ALM histologic type was associated with lower DSS and OS rates at T1 and T1a stages and lower RFS rates at T1b stage. SLN positivity was associated with lower DSS, OS, and RFS rates at T1, T1a, and T1b stages. Age was associated with lower OS rates at T1 and T1b stages. Whereas the use of systemic therapy was associated with lower DSS rates at T1a stage and RFS rates at T1b stage. In addition, the ALM group showed significantly older median age patients and higher rates of female sex, Hispanic ethnicity, nevoid cytology, non-brisk tumor-infiltrating lymphocytes, nodal metastasis, and local recurrence at every pathologic stage of thin melanoma. Our findings suggest that ALM is inherently more aggressive than other types of cutaneous melanoma. This information may be useful for prognostic stratification of patients with thin melanomas, especially to help guide the clinical decision-making for SLN biopsy and patients entering clinical trials.
Asunto(s)
Melanocitos/patología , Melanoma/secundario , Neoplasias Cutáneas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proliferación Celular , Niño , Preescolar , Toma de Decisiones Clínicas , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Metástasis Linfática , Masculino , Melanoma/mortalidad , Melanoma/terapia , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Factores de Tiempo , Adulto JovenRESUMEN
CONTEXT.: Acral lentiginous melanoma is a rare and aggressive type of cutaneous melanoma that arises on the acral skin and the nail unit. The prognostic significance of subungual anatomic site in acral lentiginous melanoma is not established. OBJECTIVE.: To assess the impact of subungual anatomic site on overall survival and disease-specific survival in acral lentiginous melanoma. DESIGN.: Retrospective cohort analysis. Clinicopathologic characteristics of 627 primary acral lentiginous melanomas (45 [7%] subungual and 582 [93%] nonsubungual) were summarized, and the impact of these characteristics on overall survival and disease-specific survival was determined using univariate and multivariable analyses. RESULTS.: No significant differences in clinicopathologic features were identified between the subungual and nonsubungual acral lentiginous melanomas. The 1-, 5-, and 10-year overall survival rates were 81%, 40%, and 28%, respectively, for subungual acral lentiginous melanoma and 94%, 59%, and 38%, respectively, for nonsubungual acral lentiginous melanoma (P = .04); risk of death was significantly higher for subungual tumors (hazard ratio [95% confidence interval] = 1.59 [1.02-2.50]; P = .04). The 1-, 5-, and 10-year disease-specific survival rates were 94%, 56%, and 48%, respectively, for subungual acral lentiginous melanoma versus 96%, 69%, and 55%, respectively, for nonsubungual acral lentiginous melanoma (P = .18). By multivariable analysis, independent poor prognostic factors included older age and ulceration for overall survival and greater Breslow thickness and sentinel lymph node positivity for overall survival and disease-specific survival. Subungual anatomic site was not an independent prognostic factor for overall or disease-specific survival. CONCLUSIONS.: Subungual anatomic site is not an independent prognostic factor for acral lentiginous melanoma.
Asunto(s)
Melanocitos/patología , Melanoma/patología , Uñas/patología , Neoplasias Cutáneas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Niño , Bases de Datos Factuales , Femenino , Humanos , Masculino , Melanoma/mortalidad , Melanoma/terapia , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Tasa de Supervivencia , Factores de Tiempo , Adulto JovenRESUMEN
We report a rare case of Wells syndrome in which a 61-year-old Caucasian male presented with three distinct skin lesions including a cutaneous bulla, an erythematous plaque, and a linear streak located on the patient's left anterior thigh, left dorsal wrist, and left anterior forearm, respectively. Histologic examination revealed diffuse and interstitial eosinophilic infiltrate admixed with lymphocytes and macrophages that predominantly involve the dermis. Nodular aggregates of eosinophils surrounding dermal collagen fibers suggestive of 'flame figures' were identified. Luna histochemical stain was used and highlighted the deposition of eosinophilic granules over the collagen bundles confirming the presence of flame figures. Laboratory workup revealed peripheral eosinophilia, but a comprehensive clinical evaluation failed to reveal a systemic disease and ultimately the diagnosis of eosinophilic cellulitis 'Wells Syndrome' was rendered. After a short course of immunosuppressive therapy, the patient experienced a complete resolution of the skin lesions on his last follow-up visit several weeks from the initial diagnosis. This case highlights the various clinical forms that Wells syndrome may present with and may serve as a good example for the use of Luna stain as a simple and cost-effective diagnostic tool that can help to arrive at the accurate diagnosis and inform therapy.
Asunto(s)
Celulitis (Flemón)/diagnóstico , Análisis Costo-Beneficio/economía , Eosinofilia/diagnóstico , Eosinófilos/patología , Piel/patología , Humanos , Persona de Mediana Edad , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/patología , SíndromeRESUMEN
We report two cases of combined cutaneous tumors composed of melanoma and carcinoma. The first tumor presented as a 5-mm pink-blue macule over the right zygomatic arch in an 85-year-old man. Shave biopsy and immunohistochemical studies revealed that the tumor was composed of melanoma (highlighted by SOX10 and MART-1, with high Ki-67 proliferative index) intermixed with nodular basal cell carcinoma (highlighted by pan-cytokeratin and Ber-EP4). The neoplastic melanocytes were confined to the basal cell carcinoma nodules, and a diagnosis of combined melanoma in situ and basal cell carcinoma was rendered. After therapeutic excision, the patient was disease-free at 9 months after the initial diagnosis. The second tumor presented as a 6-mm pink-brown crusted papule on the right forehead in an 89-year-old man. Shave biopsy and immunohistochemical studies revealed that the tumor was composed of malignant melanoma (MM) (highlighted by S100 and MART-1) intermixed with squamous cell carcinoma (SCC) (highlighted by cytokeratin and p63), and a diagnosis of combined MM-SCC was rendered. These two cases highlight the importance of recognizing these rare types of melanocytic-epithelial cutaneous neoplasms to arrive at an accurate diagnosis that may inform appropriate disease stage and therapy.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Basocelular , Melanoma , Proteínas de Neoplasias/metabolismo , Neoplasias Primarias Secundarias , Neoplasias Cutáneas , Anciano de 80 o más Años , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patología , Diagnóstico Diferencial , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/metabolismo , Melanoma/patología , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/metabolismo , Neoplasias Primarias Secundarias/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Melanoma Cutáneo MalignoRESUMEN
Melanoma is a heterogeneous neoplasm at the histomorphologic, immunophenotypic, and molecular levels. Melanoma with extreme histomorphologic heterogeneity can pose a diagnostic challenge in which the diagnosis may predominantly rely on its immunophenotypic profile. However, tumor survival and response to therapy are linked to tumor genetic heterogeneity rather than tumor morphology. Therefore, understating the molecular characteristics of such melanomas become indispensable. In this study, DNA was extracted from 11 morphologically distinct regions in eight formalin-fixed, paraffin-embedded melanomas. In each region, mutations in 50 cancer-related genes were tested using next-generation sequencing (NGS). A tumor was considered genetically heterogeneous if at least one non-overlapping mutation was identified either between the histologically distinct regions of the same tumor (intratumor heterogeneity) or among the histologically distinct regions of the paired primary and metastatic tumors within the same patient (intertumor heterogeneity). Our results revealed that genetic heterogeneity existed in all tumors as non-overlapping mutations were detected in every tested tumor (n = 5, 100%; intratumor: n = 2, 40%; intertumor: n = 3, 60%). Conversely, overlapping mutations were also detected in all the tested regions (n = 11, 100%). Melanomas exhibiting histomorphologic heterogeneity are often associated with genetic heterogeneity, which might contribute to tumor survival and poor response to therapy.