Prevalência do rearranjo do gene ROS1 em carcinoma de pulmão de células não pequenas não escamoso, EGFR e ALK negativo: análise de uma coorte brasileira / Prevalence of ROS1 gene rearrangements in EGFR-Negative and ALK-negative nonsquamous NSCLC: analysis of a Brazilian cohort

Introdução: A prevalência do câncer de pulmão tem aumentado cerca de 2% ao ano e é considerado um problema de saúde pública mundial, sendo a principal causa de morte por câncer entre homens e mulheres. O Câncer de Pulmão de Células Não Pequenas (CPCNP) representa 85-90% dos cânceres de pulmão. A detecção do rearranjo do gene ROS1, considerada um importante fator preditivo para direcionamento terapêutico, constitui uma etapa crítica no tratamento de CPCNP. Objetivo: Avaliar a prevalência do rearranjo do gene ROS1 em pacientes portadores de CPCNP não escamoso, sem mutação de EGFR ou rearranjo de ALK, diagnosticados na Região da Foz do Rio Itajaí, Estado de Santa Catarina, Brasil, no período de 02/01/2019 a 27/07/2020. Materiais e Métodos: Estudo observacional, retrospectivo e prospectivo, descrito e analítico com 95 pacientes que possuíam material de biópsia suficiente para a realização de novas análises e que não apresentavam mutação de EGFR ou rearranjo de ALK. Os pacientes com imuno-histoquímica positiva para a proteína ROS1 foram testados pelo método de FISH, utilizando-se uma sonda de DNA do tipo break-apart para o gene ROS1. Foi realizada uma análise descritiva da amostra, e os resultados foram apresentados em números absolutos e porcentagens, representados por tabelas. O teste de qui-quadrado (χ2) foi empregado para comparação das frequências entre os grupos analisados. Resultados: 52,6% foram pacientes do sexo masculino; a idade mediana foi de 64 anos; 54,7% declararam-se tabagistas; 40,0% apresentavam doença estágio IV; 29,5% apresentaram tumores com alta expressão de PD-L1. Quanto a expressão de ROS1 por imuno-histoquímica: 89,5% foram identificados como ROS1+ em 0% das células tumorais, 4,2% como ROS1+ em <70% das células, e 6,3% como ROS1+ em ≥70% das células do tumor; portanto, 10,5% apresentaram resultados positivos para expressão de ROS1. Estes pacientes foram submetidos à análise de rearranjo de ROS1 pelo método de FISH e 7 (7,4%) apresentaram resultados positivos. Conclusão: Na população estudada, a análise pelo método de FISH mostrou uma prevalência de 7,4% para rearranjos do gene ROS1

Introduction: Lung cancer prevalence has been increasing at rate of 2% per year and is considered a major public health concern worldwide, being the main cause of cancer death among women and men. Non-small cell lung cancer (NSCLC) represents 85-90% of total lung cancer. Detecting the rearrangement of the ROS1 gene is critical to the treatment of NSCLC. Objective: To assess the prevalence of the ROS1 gene rearrangement in patients diagnosed with non-squamous NSCLC patients diagnosed between January 2019 to July 2020 at Foz do Rio Itajaí, in the state of Santa Catarina, Brazil. Materials and Methods: This is a retrospective and prospective observational study Ninety-five NSCLC whose tumors were negative for EGFR mutation and ALK rearrangement and who had enough tumor tissue to carry out additional molecular analysis. Patients whose tumors were positive for ROS1 by immune-histochemistry were tested using by FISH using a break-apart DNA probe (Abbot Molecular) for the ROS1 gene. A descriptive analysis was performed and results were presented as absolute frequencies and percentages and depicted in charts. Frequencies were compared with the chi-squared test (χ2). Results: 52,6% were male, mean and median age were 65,10 and 64 years, respectively. 54,7% self-declared as smokers; 40,0% had stage IV disease; 29,5% had tumours with high expression of PD-L1. Regarding the expression of ROS1 by immunohistochemistry: 89,5% were identified as ROS1+ in 0% of cells, 4,2% as ROS1+ in <70% of cells, and 6,3% as ROS1+ in ≥70% of the cells; therefore, 10,5% displayed positive results for the expression of ROS1+. These tumors were subjected to the analysis of ROS1 rearrangement by FISH and 7 (7,4%) were positive. Conclusion: We observed 7,4% prevalence for ROS1 gene rearrangements in this pre-selected population

Oral Adenosquamous Carcinoma Mimicking a Pyogenic Granuloma: a Challenging Diagnosis

Abstract Adenosquamous carcinoma is an aggressive variant of squamous cell carcinoma. This report describes a case of adenosquamous carcinoma with clinical features of a benign lesion and discusses the differential diagnoses, especially regarding histopathological and immunohistochemical analyses. A 45-year-old male was referred to our outpatient clinic complaining about a rapid-growing enlargement in hard palate. Clinical examination revealed an erythematous and pedunculated nodule with lobulated non-ulcerated surface. Excisional biopsy was performed following clinical diagnosis of pyogenic granuloma. Histologically, the specimen consisted of areas characterizing both well-differentiated squamous cell carcinoma and true adenocarcinoma. After a broad list of immunohistochemical markers was evaluated (AE1/AE3, CEA, CK5, CK7, CK8/18, p53, p63 and Ki67), the diagnosis of adenosquamous carcinoma was rendered and the patient referred to complementary surgery. Adenosquamous carcinoma represents a challenge in diagnostic routine due to its rarity, diverse range of clinical presentations and histological features. Furthermore, classical clinical benign features may be present in malignant lesions; hence the submission of every surgical specimen to histological analysis is mandatory to provide the patient the adequate treatment.

Resumo O carcinoma adenoescamoso é uma variante agressiva do carcinoma de células escamosas. Este relato descreve um caso de carcinoma adenoescamoso que apresenta características clínicas de uma lesão benigna e discute o diagnóstico diferencial, especialmente em relação à análise histopatológica e imuno-histoquímica. Um homem de 45 anos foi encaminhado ao nosso serviço queixando-se um aumento de volume de rápido crescimento no palato duro. O exame clínico revelou um nódulo eritematoso e pedunculado com superfície lobulada não ulcerada. Foi realizada biópsia excisional seguindo a hipótese clínica de granuloma piogênico. Histologicamente o fragmento consistia em áreas de carcinoma de células escamosas bem diferenciado e áreas de adenocarcinoma verdadeiro. Após a avaliação de uma ampla lista de marcadores imuno-histoquímicos (AE1/AE3, CEA, CK5, CK7, CK8/18, p53, p63 e Ki67), o diagnóstico de carcinoma adenoescamoso foi atribuído e o paciente foi encaminhado à cirurgia complementar. O carcinoma adenoescamoso representa um desafio na rotina de diagnóstico, devido à sua raridade, diversificada gama de apresentações clínicas e características histológicas. Além disso, características clínicas benignas podem estar presentes em lesões malignas, por isto a submissão de todas as peças cirúrgicas à análise histológica é obrigatória para fornecer ao paciente o tratamento adequado.

Teratoma quístico maduro con transformación maligna: a propósito de un caso / Mature cystic teratoma with malignant transformation: a purpose of a case

Paciente femenina de 26 años de edad, quien es referida en posoperatorio de ooforectomía derecha, cuya biopsia reporta “teratoma quístico maligno, patrón epitelial tipo adenoescamoso”. Es reintervenida con laparotomía estadificadora donde se evidencia hallazgos de plastrones tumorales en peritoneo pélvico, mesocolon y epiplón, además múltiples adenopatías pre aórticas, ausencia de ovario derecho, y ovario izquierdo con tumor quístico de 6 cm de diámetro, adherido a la trompa ipsilateral y el piso pélvico. La biopsia definitiva reporta “adenocarcinoma moderadamente diferenciado con diferenciación escamosa infiltrando ovario izquierdo, pared de la trompa uterina izquierda, parametrios derecho, izquierdo, piso pélvico, peritoneo y epiplón inframesocólico”. Recibe quimioterapia adyuvante con esquema de paclitaxel y carboplatino por 4 ciclos. Al mes de terminar el tratamiento adyuvante presenta sangrado genital, evidenciándose lesión en cúpula vaginal cuya biopsia reporta “carcinoma epidermoide moderadamente diferenciado”. Se planifica tratamiento con doxorrubicina, ifosfamida y mesna combinado con radioterapia externa pélvica y braquiterapia complementaria.

We report the case of 26 year old female patient who is referred after undergoing right oophorectomy. The pathology of the surgical specimen was reported as “malignant cystic teratoma with adenosquamous epithelial pattern”. Staging laparotomy is performed. The surgical findings were: tumor implants in pelvic peritoneum, mesocolon, omentum. paraortic lymphadenopaties. Left ovary with 6 cm cystic tumor on its surface firmly adhered to the ipsilateral fallopian tube and pelvic wall. Absence of right ovary. Pathology reports “moderately differentiated adenocarcinoma with squamous differentiation infiltrates left ovary, left fallopian tube, right and left parametria, pelvic wall and inframesocolic omentum”. Adjuvant chemotherapy based on paclitaxel carboplatin for 4 cycles. One month after ending adjuvant treatment refers vaginal bleeding. After detailed gynecologic evaluation, an exophytic lesion on the vaginal vault is found. The biopsy reports “moderately differentiated squamous carcinoma”. Combined therapy based on chemotherapeutic agents (doxorubicin, iphosphamide and mesna) and external radiotherapy was scheduled.

Carcinoma adenoescamoso metastásico cerebral de origen ginecológico: a propósito de un caso / Adenosquamous carcinoma metastatic brain gynecologic origin: a purpose of a case

Es infrecuente que tumores malignos del aparato genital femenino afecten al Sistema Nervioso Central (SNC). El carcinoma del cuello uterino raramente metastiza al SNC, siendo escasa la literatura científica relacionada con esta patología. El objetivo es presentar un nuevo caso de adenocarcinoma de cuello uterino el cual fue diagnosticado en el 2005, que metastizó al SNC a los 2 años del diagnóstico inicial. Se presenta femenina de 43 años de edad quien acude al Hospital Central de San cristóbal donde se le realizó histerectomía ampliada en el 2006. En el 2007 se diagnóstica Lesión Ocupante de Espacio Cerebral que es operado resultando ser metastasis cerebral de Adenocarcinoma Escamoso. Actualmente se encuentra en condiciones clínicas estables.

Adenosquamous carcinoma of oral cavity: a case report.

An elderly man presented with a pair of soft tissue swelling, one on upper and another on lower gums, with chest pain and respiratory distress. Histopathological examination of the biopsied material showed features suggestive of adenosquamous carcinoma, but CT-guided fine needle aspiration cytology from lung mass showed evidence of non-keratinising squamous cell carcinoma. This histologic dissimilarity between primary and metastatic tumour is a characteristic feature of the lesion. Palliative radiation was given as the patient was unfit for surgery, but his condition deteriorated rapidly and treatment had to be withdrawn.

Carcinoma adenoescamoso do colo uterino mimetizando carcinoma adenóide basal: relato de um caso e revisão da literatura / Adenosquamous carcinoma of the cervix mimicking adenoid basal carcinoma: case report and review of the literature

O carcinoma adenoescamoso do colo uterino é definido como um tumor que contém uma mistura de células malignas com diferenciação escamosa e glandular. A literatura salienta a importância de se fazer esse diagnóstico, uma vez que, quando os componentes não são bem diferenciados ou não se encontram evidentes na amostra analisada, esse tumor pode ser erroneamente interpretado como carcinoma escamoso ou adenocarcinoma. O presente trabalho descreve a apresentação pouco comum de um carcinoma adenoescamoso. Após sucessivos diagnósticos citológicos não concordantes e complicados por uma história de sangramento uterino anormal ocasionado por endometriose cervical, a paciente de 47 anos foi submetida a histerectomia total, obtendo diagnóstico definitivo. Esse particular tumor aqui relatado foi diagnosticado como carcinoma adenoescamoso, mas em muitos aspectos apresentou-se semelhante ao carcinoma adenóide basal. Elementos característicos do carcinoma adenóide basal, como presença de lesão intra-epitelial escamosa na superfície, diferenciação escamosa e glandular no centro dos blocos neoplásicos e células basalóides na profundidade da lesão, foram observados em nosso caso. Em contrapartida, os seguintes elementos normalmente não observados no carcinoma adenóide basal estavam presentes: atipias e figuras de mitose nas células indiferenciadas da profundidade do tumor e lesão intra-epitelial escamomucinosa (SMILE) na superfície. Fatores epidemiológicos e clínicos, como idade (47), raça (branca) e forma de apresentação clínica (massa visível na inspeção cervical), também colaboraram para afastar esse diagnóstico diferencial. Outros diagnósticos diferenciais do carcinoma adenoescamoso do colo uterino incluem o carcinoma puramente escamoso ou glandular, o tumor de colisão e o adenocarcinoma de endométrio com diferenciação escamosa invadindo o colo uterino.

Adenosquamous carcinoma of the uterine cervix is defined as a tumor that contains a mixture of malignant cells with squamous and glandular differentiation. The literature points to the importance of making this diagnosis when the cellular components are still well differentiated in the sample, otherwise the tumor may be erroneously interpreted as squamous carcinoma or adenocarcinoma. This study describes an unusual presentation of a adenosquamous carcinoma in a 47 year old patient. After conflicting cytological diagnoses and a history of abnormal uterine bleeding caused by cervical endometriosis, the patient was subjected to radical hysterectomy and a final diagnosis was obtained. The tumor was diagnosed as adenosquamous carcinoma. In many aspects, however, it was similar to the adenoid basal carcinoma. Characteristic features of the adenoid basal carcinoma such as the presence of high-grade squamous intraepithelial lesion in the surface epithelium, squamous and glandular differentiation in the center of the neoplastic mass, and basaloid cells in deep areas of the tumor were observed. Therefore, the following elements usually absent from adenoid basal carcinoma were present in this case: atypia and mitotic figures in undifferentiated cells, squamous-mucinous intraepithelial lesion (SMILE) in the superficial areas. Epidemiological and clinical data, such as patient age (47), race (white) and presentation (a cervical mass), concurred to exclude the diagnosis of adenoid basal carcinoma. Other differential diagnoses include pure squamous carcinoma or adenocarcinoma, collision tumor, and endometrial adenocarcinoma with squamous differentiation invading the uterine cervix.

Adenosquamous Carcinoma of Extrahepatic Bile Duct: A Case Report

Most malignant tumors originating from the biliary tract are adenocarcinomas, and adenosqamous carcinoma of Klatskin's tumor is a very rare finding. An 83-yr-old man was admitted to our hospital because of jaundice. The abdominal computed tomography and magnetic resonance cholangiopancreatography revealed wall thickening and luminal stenosis of both the intrahepatic duct confluent portion and the common hepatic duct. These findings were compatible with Klatskin's tumor, Bismuth type III. Considering the patient's old age, palliative combined modality therapy was performed. After percutaneous transhepatic biliary drainage, biopsy was performed via percutaneous transhepatic cholangioscopy. The histopathologic findings showed adenosquamous carcinoma. External radiotherapy and intraluminal brachytherapy through the endobiliary Y-type stent were then done. Nine months after the radiotherapy, the laboratory findings and the abdominal computed tomography revealed biliary obstruction and progressive hepatic metastasis. The combined modality therapy of external radiotherapy, intraluminal brachytherapy and stenting assisted him to live a normal life until he finally experienced biliary obstruction.

A Case of Adenosquamous Carcinoma of the Papilla of Vater / 대한소화기학회지

Adenosquamous carcinoma of the papilla of Vater is a rare tumor and only a few cases have been reported so far. Here, we report a case of adenosquamous carcinoma in a 76-year-old male who presented with jaundice and right upper quadrant abdominal pain. Ultrasonography and enhanced abdominal CT scans showed dilated common bile duct (CBD) and intrahepatic bile duct (IHD) with a suspicious obstructing mass in distal CBD. On endoscopy, obstructing and ulcerated mass was noted on the papilla of Vater. Histopathological inspection of the biopsied specimens from mass showed adenosquamous cell carcinoma of the papilla of Vater. Since the patient refused operation, we inserted a self-expandable metallic stent in distal CBD. This is the first case report on adenosquamous carcinoma of the papilla of Vater in Korea.

Primary Adenosquamous Carcinoma of the Liver: A Case Report / 대한간학회지

Primary adenosquamous cell carcinoma of the liver, a variant of cholangiocarcinoma is very rare disease and its prognosis is known to be very poor. We describe here a case of primary adenosquamous carcinoma of the liver. The patient was a 60-year-old woman who complained of an eight-month history of intermittent upper abdominal pain. Abdominal computed tomography scan revealed a low density mass and intrahepatic duct stones within the dilated left intrahepatic duct in the left lateral segment. Needle biopsy of the mass was done and the histologic diagnosis was cholangiocarcinoma. Left lobectomy was then performed. Upon gross examination, there was a well defined solid mass and intrahepatic duct stone in the dilated bile duct. Microscopically, the tumor was composed of both adenocarcinoma and squamous cell carcinoma.

Adenosquamous carcinoma of the rectum: a case report.

Adenosquamous carcinoma is defined as a tumor with well defined malignant glandular and squamous components and the potential for both components to metastases. This tumor is extremely rare in colon and rectum with an incidence of less than 0.2%. Adenosquamous carcinoma of rectum should be distinguished from collision tumor with exemption of all lesions located distal to a level of 7 cm above the dentate line. Here we present a case of rare type adenosquamous carcinoma in rectum in a 29 year old female.

Significance of mucin secretion in carcinoma of uterine cervix.

Biopsies from 300 cases with clinical diagnosis of carcinoma cervix were subjected to H&E staining, PAS with diastase and alcian blue at pH 2.5. Interpretation of cases on basis of H&E staining alone and on basis of H&E and mucin stains was done and results compared with each other. Categorization into squamous cell carcinoma (well, moderately & poorly differentiated), adenocarcinoma and mixed carcinoma was done. Morphologic assessment of cases of H&E stain revealed 282 (94%) cases of squamous cell carcinoma, 8 (2.66%) cases of adeno carcinoma and 10 (3.38%) cases of mixed carcinoma respectively. While on the basis of H&E and mucin stains, squamous cell carcinoma case turned out to be 266 (88.66%) in number; mixed carcinomas which included adenosquamous carcinoma and squamous cell carcinoma with mucin secretion accounted for 26 (8.66%) of cases, number of adenocarcinoma was unchanged i.e. 8 (2.66%). 16 of 282 cases (5.6%) diagnosed as squamous cell carcinoma on H&E stain alone were reclassified as mixed carcinoma on inclusion of mucin stains. Thus mucin stains are very helpful in deciding the types of carcinoma cervix and should be done in all cases of carcinoma cervix in order to avoid errors in diagnosis and to detect poorly differentiated mixed carcinomas, which may escape detection by H&E staining.

Accuracy of cytological findings in abnormal cervical smears by cytohistologic comparison.

To investigate the accuracy rates of cytology in abnormal cervical smears and the factors contributing to a discrepant diagnosis between cytology and histology repots of cervical intraepithelial and invasive neoplasm. During the four-year period 1993 to 1996, abnormal cervical smear findings, which were followed by cervical biopsy, were available in 709 patients. The cytology and histology slides were reviewed in each case. The accuracy rates of cytology before and after review were investigated. The accuracy rate of cytology was 48%. Following review it became 56%, mainly due to a reduction in the number of cases in which the smear showed a lesser degree of CIN than did the biopsy. The proportion of cases in which the cytological impression of CIN was more severe than the histology was minimally altered. The results suggest that difficulty in the interpretation of cervical smear as well as sampling errors are responsible for reduced accuracy even in smears which are considered representative of the pathological process.

"Glassy cell carcinoma" do colo uterino: relato de dois casos / Glassy cell carcinoma of the uterine cervix: two case reports

Os autores apresentam dois casos de "glassy cell carcinoma" do colo uterino, diagnosticados por biópsias dirigidas deste órgäo. Este tumor é classificado como um carcinoma adenoescamoso pouco diferenciado e de mau prognóstico, especialmente quando comparado com as neoplasias mais frequentes do colo uterino. Apesar de possuir características próprias, como distribuiçäo etária, invasäo nodal precoce, curso agressivo, baixa resposta ao tratamento e associaçäo frequente com gravidez e multiparidade, alguns autores näo o consideram como uma entidade clinicopatológica distina

Carcinoma adenoescamoso de células en vidrio esmerilado / Adenoscamous carcinoma of cells in emery glass

Se presenta un caso clínico de carcinoma de células en vidrio esmerilado de cuello uterino, en una mujer joven, embarazada, de curso agresivo, con rápida progresión a estadio clínico fuera del alcance terapéutico