RESUMO
Apart from the lethal midline carcinoma (NUT carcinoma), NUTM1 translocation has also been reported in mesenchymal tumors, but is exceedingly rare. Here, we describe a series of 8 NUTM1 -rearranged sarcomas to further characterize the clinicopathologic features of this emerging entity. This cohort included 2 males and 6 females with age ranging from 24 to 64 years (mean: 51 y; median: 56 y). Tumors occurred in the colon (2), abdomen (2), jejunum (1), esophagus (1), lung (1) and infraorbital region (1). At diagnosis, 6 patients presented with metastatic disease. Tumor size ranged from 1 to 10.5 cm (mean: 6 cm; median: 5.5 cm). Histologically, 4 tumors were composed of primitive small round cells to epithelioid cells intermixed with variable spindle cells, while 3 tumors consisted exclusively of small round cells to epithelioid cells and 1 tumor consisted predominantly of high-grade spindle cells. The neoplastic cells were arranged in solid sheets, nests, or intersecting fascicles. Mitotic activity ranged from 1 to 15/10 HPF (median: 5/10 HPF). Other features included rhabdoid phenotype (4/8), pronounced nuclear convolutions (2/8), prominent stromal hyalinization (2/8), focally myxoid stroma (1/8), foci of osteoclasts (1/8), and necrosis (1/8). By immunohistochemistry, all tumors showed diffuse and strong nuclear staining of NUT protein, with variable expression of pancytokeratin (AE1/AE3) (2/8), CK18 (1/8), CD99 (3/8), NKX2.2 (2/8), cyclin D1 (2/8), desmin (2/8), BCOR (2/8), S100 (1/8), TLE1 (1/8), and synaptophysin (1/8). Seven of 8 tumors demonstrated NUTM1 rearrangement by fluorescence in situ hybridization analysis. RNA-sequencing analysis identified MXD4::NUTM1 (3/7), MXI1::NUTM1 (3/7), and MGA::NUTM1 (1/7) fusions, respectively. DNA-based methylation profiling performed in 2 cases revealed distinct methylation cluster differing from those of NUT carcinoma and undifferentiated small round cell and spindle cell sarcomas. At follow-up (range: 4 to 24 mo), 1 patient experienced recurrence at 8.5 months, 4 patients were alive with metastatic disease (5, 10, 11, and 24 mo after diagnosis), 3 patients remained well with no signs of recurrence or metastasis (4, 6, and 12 mo after diagnosis). Our study further demonstrated that NUTM1 -rearranged sarcoma had a broad range of clinicopathologic spectrum. NUT immunohistochemistry should be included in the diagnostic approach of monotonous undifferentiated small round, epithelioid to high-grade spindle cell malignancies that difficult to classify by conventional means. DNA-based methylation profiling might provide a promising tool in the epigenetic classification of undifferentiated sarcomas.
Assuntos
Biomarcadores Tumorais , Rearranjo Gênico , Proteínas de Neoplasias , Proteínas Nucleares , Sarcoma , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Sarcoma/genética , Sarcoma/patologia , Sarcoma/química , Proteínas Nucleares/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Adulto Jovem , Proteínas de Neoplasias/genética , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Fenótipo , Predisposição Genética para Doença , Proteína Homeobox Nkx-2.2 , Fatores de Transcrição , Proteínas de HomeodomínioRESUMO
The number of recognized sarcoma types harboring targetable molecular alterations continues to increase. Here we present 25 examples of a distinctive myofibroblastic tumor, provisionally termed "myxoid inflammatory myofibroblastic sarcoma," which might be related to inflammatory myofibroblastic tumor, and which occurred in 13 males (52%) and 12 females at a median age of 37 years (range: 7 to 79 years). Primary tumor sites were peritoneum (18 patients; 72%), paratesticular (2; 8%), chest wall (1), upper extremity (1), esophagus (1), retroperitoneum (1), and uterus (1). Nine peritoneal tumors (50%) were multifocal at presentation; all other tumors were unifocal. Tumors showed bland-to-mildly-atypical neoplastic myofibroblasts in a myxoid stroma, with prominent inflammatory infiltrates in 22 cases (88%). Most tumors showed delicate branching stromal vessels like those of myxoid liposarcoma, and most showed infiltrative growth through non-neoplastic tissue. Immunohistochemistry demonstrated expression of SMA (19/25 tumors; 76%), desmin (13/22; 59%), and CD30 (5/11; 45%), while ALK was expressed in 1 tumor (of 25; 4%) that was negative for ALK rearrangement. Sequencing of 11 tumors showed seven to harbor tyrosine kinase fusions (4 PDGFRB , 2 PML :: JAK1 , 1 SEC31A :: PDGFRA ). Two instead harbored hot spot KRAS mutations (G12V and Q61H), and 2 were negative for known driving alterations. Clinical follow-up was available for 18 patients (72%; median: 2.7 years; range: 4 mo-12.3 years). Nine patients (50%) were alive with no evidence of disease, 5 (28%) died of disease, and 4 (22%) were alive with disease. Seven patients (39%) experienced peritoneal relapse or distant metastasis. Two patients showed disease progression on conventional, nontargeted chemotherapy. The patient whose tumor harbored SEC31A :: PDGFRA was treated after multiple relapses with imatinib and sunitinib therapy, with progression-free periods of 5 and 2 years, respectively. Despite its bland appearance, myxoid inflammatory myofibroblastic sarcoma harbors a significant risk for disseminated disease, particularly when it occurs in the peritoneum. Targeted therapy could be considered for patients with disseminated disease.
Assuntos
Biomarcadores Tumorais , Miofibroblastos , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adolescente , Adulto Jovem , Criança , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Miofibroblastos/patologia , Miofibroblastos/química , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/terapia , Sarcoma/patologia , Sarcoma/genética , Sarcoma/química , Sarcoma/mortalidade , Imuno-HistoquímicaRESUMO
O estudo imunoistoquímico tem sido empregado para a avaliação do diagnóstico diferencial de neoplasia. OBJETIVO: Avaliar o uso do método nos casos de câncer de cabeça e pescoço. MÉTODO: Estudo retrospectivo de casos do Registro Hospitalar de Câncer da instituição. RESULTADOS: De 704 resultados anatomopatológicos, a imunoistoquímica foi realizada em 76 (11%). A maioria correspondeu a carcinomas - 85,80% e, destes, 83,66% eram epidermoides. Todos os exames foram para fins diagnósticos. Houve maior frequência para o uso de 34BE12 (37,18%), AE1/AE3 (35,90%), 35BH11 (28,21%), CD45 (25,64%), CD20 (24,36%), CD30 (24,36%), CK7 (23,08%) e CD3 (23,08%). CONCLUSÃO: A imunoistoquímica foi usada em 10,67% dos casos de câncer de cabeça e pescoço submetidos a exame anatomopatológico, sendo maior para os carcinomas -- 5,26%. Na determinação do carcinoma epidermoide, seu uso foi de 18,42% do total de neoplasias.
Immunohistochemistry (IHC) has been employed in the differential diagnosis of tumors. OBJECTIVE: To assess the use of IHC in cases of head and neck tumor. METHOD: This is a retrospective study of the cases included in the Cancer Registry of the institution. RESULTS: IHC was used in 76 (11%) of 704 pathology tests. Most cases were carcinomas (85.80%), and 83.66% of them were squamous cell carcinomas. All tests were done with diagnostic purposes. The most frequently used antibodies were 34BE12 (37.18%), AE1/AE3 (35.9%), 35BH11 (28.21%), CD45 (25.64%), CD20 (24.36%), CD30 (24.36%), CK7 (23.08%) and CD3 (23.08%). CONCLUSIONS: IHC was used in 10.67% of the head and neck tumor cases submitted to pathology testing, mostly for carcinoma (5.26%). In the determination of squamous cell carcinoma, IHC accounted for 18.42% of all tumors.