Genomic landscapes of ovarian clear cell carcinoma from latin countries reveal aberrations linked to survival and progression.

BACKGROUND: Ovarian clear cell carcinomas (OCCCs) are rare, aggressive and chemoresistant tumors. Geographical and ethnic differences in the incidence of OCCC have been reported with a higher incidence in Asiatic countries. There is a paucity of information regarding OCCC in Latin America (LA) and other countries. METHODS: Here, we characterized two cohorts of 33 patients with OCCC from LA (24 from Brazil and 9 from Costa Rica) and a cohort of 27 patients from Spain. Genomic analysis was performed for 26 OCCC using the OncoScan platform. Tumors were classified according to their genomic landscapes into subgroups. Clinical parameters were related to the frequency of genomic aberrations. RESULTS: The median overall survival (OS) was not significantly different between the cohorts. Genomic landscapes were characterized by different homologous recombination deficiency (HRD) levels. No difference in the distribution of genomic landscapes profiles was detected between patients from the different cohorts. OCCCs with MYC-amplified tumors harboring a concomitant loss of a region in chromosome 13q12-q13 that includes the BRCA2 gene had the longest OS. In contrast, patients carrying a high number (> 30) of total copy number (CN) aberrations with no concomitant alterations in MYC and BRCA2 genes presented the shortest OS. Furthermore, amplification of the ASH1L gene was also associated with a shorter OS. Initial-stage OCCCs with early progression were characterized by gains in the JNK1 and MKL1 genes. CONCLUSIONS: Our results provide new data from understudied OCCC populations and reveal new potential markers for OCCCs.

Value of Immunohistochemistry to Differentiate Digital Papillary Adenocarcinoma From Acral Hidradenoma With Papillary Structures.

ABSTRACT: Digital papillary adenocarcinoma is a malignant adnexal tumor with a predilection for acral sites. Hidradenoma is a benign solid and cystic sweat gland neoplasm with focal ductal and glandular differentiation and good outcomes. Hidradenomas can occur at acral sites and show papillary structures; for this reason, they are included in the differential diagnosis of digital papillary adenocarcinoma, and immunohistochemistry is a valuable tool in this scenario. We described a case of a 43-year-old man with an epithelial tumor showing papillary structures in the intermediate phalanx of the fourth finger. There was diffuse positivity for p63 and negativity for S100 protein, suggesting that this tumor was an acral hidradenoma with papillary structures.

Clear cell carcinoma arising from abdominal wall endometriosis-a report on two cases and literature review.

BACKGROUND: Malignant transformation of abdominal wall endometriosis is extremely rare. Clear cell carcinoma and endometrioid carcinoma are the two most prevalent histological subtypes of malignant endometriosis. To date, approximately, thirty cases of clear cell carcinoma arising from abdominal wall endometriosis have been described worldwide. CASE PRESENTATION: We report two cases of clear cell carcinoma developing postoperatively in the anterior abdominal wall in women with a history of extensive endometriosis. Histopathology of the resected abdominal wall tumor demonstrated benign endometriosis contiguous with features of clear cell carcinoma. These histological features satisfied Sampson's criteria which are required for diagnosing malignant endometriosis. Both patients were successfully managed with platinum-based adjuvant chemotherapy following cytoreductive surgery. CONCLUSION: Clear cell carcinoma arising from the abdominal wall endometriosis is a rare, highly aggressive cancer with a propensity to recur or metastasize. Due to the limited publications on this clinical entity, there are no clearly established protocols regarding adjuvant treatment, and an evaluation of prognostic factors is lacking. Clinicians must have a high index of suspicion for malignant endometriosis of the abdominal wall, particularly in patients with an abdominal wall mass, prior abdominal surgery, and long-standing endometriosis. By presenting our case, we expect to raise awareness and study of this rare endometriosis-related neoplasm.

Hyalinizing clear cell carcinoma of minor salivary glands: A case report with uncommon presentation.

Hyalinizing clear cell carcinoma (HCCC) is a rare malignant neoplasm that commonly arises in the palate, whose occurrence in other intraoral sites is extremely uncommon. We present a case of a 74 years old afro-descendant female presenting an asymptomatic swelling in the lingual region of teeth 32, 33 and 34, with four months of Evolution, promoting an area of bone resorption with imprecise margins. Incisional biopsy revealed proliferative nests of clear cells within a hyalinized fibrous connective tissue. Tumor cells showed immunohistochemical positivity for AE1/AE3, CK7, p63 and ki67 (30%), but negativity for CK14, CK19 and α-SMA. The final diagnosis was HCCC. The tumor was subjected to surgical resection and no recurrence was observed after 16 months. CCCH is a low-grade malignant tumor that must be differentiated from other malignant clear cell tumors, including epithelial-myoepithelial carcinoma, myoepithelial carcinoma, mucin-depleted mucoepidermoid carcinoma and metastatic renal clear cell carcinoma. Immunohistochemistry is a useful tool to achieve the correct diagnosis and provide the proper therapy for the tumor.

Malignant lesion of clear cells: A diagnostic challenge of an unusual presentation mimicking a benign lesion.

In the oral cavity, a broad spectrum of differential diagnostics includes lesions composed of clear cells. Under this umbrella, Clear Cell Odontogenic Carcinoma (CCOC) and Hyalinizing Clear Cell Carcinoma (HCCC) are rare malignancies that arise from different histological origins. However, the histology is similar; therefore, differentiation of CCOC and HCCC lesions is difficult and, in some cases, impossible to distinguish morphologically and immunohistochemically. Herein, we report an unusual presentation of a well-defined nodular lesion affecting the maxillary gingiva in a 19-year-old female, which presented clinically as a benign or reaction etiology lesion. Microscopic evaluation showed a tumor composed of cell sheets with clear cytoplasm, separated by septa of fibrous tissue and invading the connective tissue. Tumor cells were positive for p63 and AE1/AE3 and negative for PAX8, smooth muscle actin (AML) and estrogen receptor. The diagnosis was carcinoma with a clear cell pattern, and it was not possible to distinguish between HCCC and CCOC. In this study, clinicopathologic, histologic, and immunohistochemistry features of CCOC and HCCC were discussed due to the challenging histological diagnosis. Radical surgical treatment and rehabilitation of the patient through graft and dental implants were performed. The patient is under follow-up with no signs of recurrence.

Bilateral diffuse uveal melanocytic proliferation with multifocal diffuse integumentary melanocytic proliferation paraneoplastic syndrome: A case report.

Bilateral diffuse uveal melanocytic proliferation (B-DUMP) is a rare paraneoplastic syndrome typically presenting with bilateral visual loss. B-DUMP is associated with extraocular systemic malignancies with the most common being lung cancer in males and uro-gynaecological cancer in females (mainly ovarian cancer). Cutaneous and/or mucosal involvement in patients with B-DUMP has been reported but it is not well characterised. Herein, we present a female in her 70s with diagnosis of stage IV vaginal clear-cell carcinoma and metastatic melanoma of unknown primary that developed progressive bilateral loss of visual acuity compatible with 'B-DUMP'. Simultaneously, she developed multifocal bilateral bluish-greyish patches on the skin that were shown to have a proliferation of dermal melanocytes. We propose that the clinical and histopathologic cutaneous findings seen in patients with B-DUMP be termed 'diffuse integumentary melanocytic proliferation (DIMP)'.

Bevacizumab in recurrent ovarian cancer: could it be particularly effective in patients with clear cell carcinoma?

PURPOSE: Treatment of recurrent ovarian carcinoma is a challenge, particularly for the clear cell (CCC) subtype. However, there is a preclinical rationale that these patients could achieve a benefit from antiangiogenic therapy. To assess this hypothesis, we used the growth modulation index (GMI), which represents an intrapatient comparison of two successive progression-free survival (PFS). METHODS: We conducted a retrospective real-world study performed on 34 patients with recurrent ovarian cancer, treated with bevacizumab-containing regimens from January 2009 to December 2017. The primary endpoint was GMI. An established cut-off > 1.33 was defined as a sign of drug activity. RESULTS: 73.5% of patients had high-grade serous ovarian carcinoma (HGSOC), and 17.7% had CCC; 70.6% of patients received carboplatin/gemcitabine/bevacizumab, and 29.4% received weekly paclitaxel/bevacizumab. According to histological subtype, the overall response rate and median PFS were 52% and 14 months for HGSOC and 83.3% and 20 months for CCC, respectively. The overall population median GMI was 0.99; it was 0.95 and 2.36 for HGSOC and CCC, respectively. CCC subtype was significantly correlated with GMI > 1.33 (odds ratio 41.67; 95% confidence interval 3.6-486.94; p = .03). CONCLUSION: Adding bevacizumab to chemotherapy in recurrent CCC is associated with a remarkable benefit in this cohort. The efficacy of antiangiogenic drugs in CCC warrants further prospective evaluation.

Clear-cell carcinoma with sarcomatoid pattern, associated with gingival metastasis. Case report and review of the literature.

ANTECEDENTES: El carcinoma renal con diferenciación sarcomatoide confiere un pronóstico sombrío por su evolución metastásica; a mucosa oral corresponde menos del 1%. CASO CLÍNICO: Mujer de 66 años, tumor dependiente de riñón izquierdo con reporte de patología de carcinoma renal de células claras patrón sarcomatoide, tumor gingival en maxilar izquierdo, biopsia con metástasis de células claras sarcomatoide. Recibió radioterapia local. Progresó con metástasis a sistema nervioso central, pulmonar, mediastinal y suprarrenal. CONCLUSIONES: La presentación clínica de tumores renales en la mucosa oral es rara. La presencia de diferenciación sarcomatoide implica un reto terapéutico por la respuesta a las terapias sistémicas existentes. Los avances en fármacos con actividad inmunitaria podrían mejorar las tasas de respuesta. BACKGROUND: The renal carcinoma with sarcomatoid differentiation confers a poor prognosis due to its metastatic evolution, less than 1% corresponds to oral mucosa. CASE REPORT: 66 year old female, left kidney tumor, with pathology report clear cell renal carcinoma, with sarcomatoid pattern, gingival tumor in the left maxilla, biopsy with sarcomatoid metastases, received local radiotherapy. It progressed with metastases to the central nervous system, pulmonary, mediastinal and adrenal. ­. CONCLUSIONS: The clinical presentation of kidney tumors in oral mucosa is rare, the presence of sarcomatoid differentiation implies a therapeutic challenge due to the response to existing systemic therapies, advances in drugs with immunological activity could improve response rates.

Analysis of the relationship between hospital characteristics and survival in ovarian cancer: A historical cohort.

BACKGROUND AND OBJECTIVES: The management of ovarian cancer requires complex surgical and medical interventions. Specialized care is associated with superior outcomes in early and advanced stages. This study aimed to estimate the effect of hospital characteristics on the overall survival of women with epithelial ovarian cancer. METHODS: We established a cohort with data recorded by the Fundação Oncocentro de São Paulo cancer registry. We included 6111 women treated for ovarian cancer in the state of Sao Paulo from January 2000 to December 2018. From 76 hospitals analyzed, 7 were high volume (20 or more cases a year) and 69 low volume. Twenty-nine were teaching and 47 community hospitals. A 10-year survival was analyzed using the Kaplan-Meyer estimator and the Cox model. RESULTS: Fifty-two percent of the epithelial ovarian cancer patients were treated in high-volume hospitals. High-volume - (HR, 0.86; 95% CI, 0.8-0.92; P < .001) and teaching - (HR, 0.91; 95% CI, 0.85-0.99; P = .019) were hospital characteristics associated with low risk of death in 10 years. CONCLUSIONS: High-volume and teaching hospitals are associated with better overall survival in ovarian cancer. Our data suggest that both hospital characteristics are important indicators of good quality of care in ovarian cancer treatment.

Estudo clínico-patológico do carcinoma de células claras de glândula salivar / Clinical pathological study of clear cell carcinoma of the salivary gland

Na classificação da Organização Mundial de Saúde (OMS) de 2017 foram relatados 11 tipos de neoplasias benignas e 20 tipos de neoplasias malignas das glândulas salivares. Dentre estes últimos está o carcinoma de células claras de glândula salivar, uma neoplasia rara que corresponde a menos de 1% dos carcinomas de glândulas salivares. Tem no seu aspecto histológico semelhança com outras neoplasias que também apresentam células claras, tendo a imuno-histoquímica e os testes moleculares importante papel para seu diagnóstico. O objetivo do presente trabalho foi avaliar os aspectos histopatológicos, imuno-histoquímicos e biomoleculares, correlacionando com aspectos clínicos, dos casos carcinomas de células claras de glândula salivar, diagnosticados no serviço de Patologia Oral e Maxilofacial da Faculdade de Odontologia da Universidade de São Paulo (USP) diagnosticados no período entre 1997 e 2018. Em todos os casos foram avaliados os cortes histológicos, reações de imuno-histoquímica para citoqueratinas 7 e 14 (CK7 e CK14), proteína p63, proteína S-100 e actina de musculo liso (SMA), além de teste molecular da reação em cadeia da polimerase (PCR) em tempo real para pesquisa da expressão do gene de fusão EWSR1-ATF1. No levantamento dos casos do serviço de Patologia Oral e Maxilofacial da Faculdade de odontologia da USP no período de 1997 até 2018 observamos 11 lesões com as características histológicas e imuno-histoquímicas para se caracterizar como carcinoma de células claras de glândulas salivares, sendo 81,81% em mulheres, 77,77% de cor da pele branca, média de idade 56,42 anos e as regiões mais acometidas foram o palato e a mucosa jugal com 36,36% dos casos cada. Histologicamente nove casos apresentavam hialinização; e invasão neural e necrose estavam presentes em 6 e 2 dos casos respectivamente. Todos os casos foram positivos para ácido periódico-Schiff (PAS), e na imuno-histoquímica CK7 e CK14 estavam presentes em todos os casos, assim como p63. Já S-100 e SMA foram negativos em todos. No teste molecular de PCR apenas duas lesões mostraram o gene de fusão EWSR1-ATF1. Concluímos que o carcinoma de células claras é mais prevalente em mulheres com idade entre 50 e 60 anos, com predileção pelo palato. A histologia associada à imuno-histoquímica muitas vezes é suficiente para se fechar esse diagnóstico, por se tratar de uma lesão com um só tipo celular. A hialinização nem sempre está presente na lesão e a invasão neural é muito comum. Os testes moleculares devem ser utilizados como auxilio no diagnóstico, e o resultado da reação em cadeia da polimerase (PCR) para o gene EWSR1-ATF1 é fiel apenas em lesões recentes.

Adenocarcinoma de células claras de colo uterino em paciente gestante / Adenocarcinoma of clear uterine cervical cells in pregnant patient

O adenocarcinoma de células claras (CCA) primário de colo uterino em pacientes jovens é uma doença rara, de etiologia desconhecida e que no passado estava associada ao uso do dietilestilbestrol durante a gestação, quando sua comercialização era permitida. A queixa mais frequente do CCA é o sangramento vaginal irregular. Relatamos o caso de CCA de endocérvice em paciente jovem que engravidou naturalmente após o diagnóstico da neoplasia.(AU)

Primary cervical clear cell adenocarcinoma (CCA) in young patients is a rare disease of unknown etiology in the past associated with the use of diethylstilbestrol during pregnancy when its use was permitted. The most frequent complaint is irregular vaginal bleeding. We report the case of endocervous clear cell adenocarcinoma in a young patient who became naturally pregnant, even after the diagnosis of the neoplasia.(AU)

Padrão histopatológico e incidência de carcinomatose peritoneal ao diagnóstico em mulheres com câncer de ovário / Histopathological pattern and incidence of peritoneal carcinomatosis at diagnosis in women with ovarian cancer

Objetivo: Descrever o padrão histopatológico e identificar a incidência de carcinomatose peritoneal no momento do diagnóstico de mulheres diagnosticadas com neoplasia de ovário. Métodos: Trata-se de um estudo transversal e descritivo, baseado na análise secundária de dados correspondentes aos prontuários de mulheres adultas com diagnóstico de neoplasia de ovário de um serviço de referência em oncologia clínica. Foram analisados 40 prontuários entre janeiro de 2007 e janeiro de 2017. Resultados: Ao estadiamento segundo o sistema da International Federation of Gynecology and Obstetrics, três mulheres (7,5%) apresentavam estadiamento clínico (EC) II, três (77,5%) estágio ECIII com carcinomatose peritoneal/invasão da pelve e seis (15%) estágio ECIV com metástases à distância, especialmente para pulmão e fígado. Em relação ao padrão histopatológico, 20 mulheres apresentaram adenocarcinoma seroso papilífero de alto grau (50%), 4 (10%) adenocarcinoma seroso papilífero de baixo grau, 3 (7,5%) adenocarcinoma endometrioide, 3 (7,5%) tumor de teca/granulosa, 3 (7,5%) carcinoma de células claras, 3 (7,5%) tumores não classificados, 2 (5%) disgerminoma e 2 (5%) com cistoadenocarcinoma mucinosos. Conclusão: É nítida a necessidade de mais estudos envolvendo essa patologia, de modo a favorecer o diagnóstico e a intervenção em estágios mais precoces e reduzir desfechos desfavoráveis. (AU)

Objective: To describe the histopathological pattern, and to identify the incidence of peritoneal carcinomatosis at the time of the diagnosis of women diagnosed with ovarian neoplasm. Methods: This is a cross-sectional and descriptive study, based on the secondary analysis of data corresponding to the medical records of adult women diagnosed with ovarian neoplasm in a reference service of clinical oncology. A total of 40 medical records were analyzed between January 2007 and January 2017. Results: At the staging (FIGO system) of the International Federation of Gynecology and Obstetrics, three women (7.5%) had clinical staging (EC) II staging, 31 (77.5%) were in the ECIII stage, with peritoneal carcinomatosis/pelvic invasion, six (15%) were in the ECIV stage, with metastases at a distance, especially to lung and liver. Regarding the histopathological pattern, twenty women had high-grade papillary serous adenocarcinoma (50%), 4 (10%) with low-grade papillary serous adenocarcinoma, 3 (7.5%) with endometrioid adenocarcinoma, 3 (7.5%) with granulosa-theca tumor, 3 (7.5%) with clear cell carcinoma, 3 (7.5%) with unclassified tumors, 2 (5%) with dysgerminoma, two (5%) with mucinous cystadenocarcinoma. Conclusions: There is a clear need for further studies involving this pathology, in order to favor diagnosis and intervention at earlier stages and to reduce unfavorable outcomes. (AU)

Expressão de FOXP3 e resposta inflamatória em carcinomas de células renais de células claras / FOXP3 expression and inflammatory response in clear cell renal cell carcinomas

Introdução: Nas últimas décadas, progressos significativos foram feitos no manejo do carcinoma de células renais no cenário de doença avançada ou metastática. O uso de imunoterápicos estão aumentando tendo em vista que as células inatas e adaptativas do sistema imune desempenham um papel importante na regulação do crescimento do câncer. Objetivos: Os autores avaliaram as expressões imuno-histoquímicas de FOXP3, CD4 e CD8 e seus impactos prognósticos na sobrevida global e as compararam com fatores clínicos e patológicos. Metodologia: As expressões imuno-histoquímicas de FOXP3, CD4 e CD8 foram analisadas em 103 casos de carcinomas renais de células claras dispostos em tissue microarray. Para análise de seu impacto na sobrevida e associação com variáveis clínicas, dados epidemiológicos e clínicos foram coletados. Resultados: Em uma análise univariada, a razão de linfócitos CD4+/CD8+ apresentou impacto na sobrevida câncer específica (SCE) (p=0,045). Conclusão: A relação de linfócitos CD4+/CD8+ esteve associada a piores taxas de SCE. Nenhuma das variáveis clínicas e anatomopatológicas estudadas mostrou relação significativa com linfócitos positivos para FOXP3, CD4 e CD8 (AU)

Introduction: Significant progress has been made in the management of renal cell carcinoma during the last decades in the advanced or metastatic scenario. The use of immunotherapy is increasing as innate and adaptive cells of the immune system play an important role in regulating cancer growth. Objectives: The authors evaluated the immunohistochemical expressions of FOXP3, CD4 and CD8 and their prognostic impacts on overall survival and compared them with clinical and pathological factors. Methodology: Epidemiological and clinical data were collected. Immunohistochemical expressions were analyzed in 103 cases arranged in tissue microarray. Results: In a univariate analysis, the CD4+/CD8+ lymphocyte ratio impacted cancer-specific survival (ECS) (p = 0.045). Conclusion: The ratio of CD4+/CD8+ lymphocytes was associated with worse ECS rates. None of the clinical and anatomopathological variables studied showed a significant relationship with FOXP3, CD4 and CD8 positive lymphocytes (AU)

Malignant transformation of abdominal wall endometriosis to clear cell carcinoma: case report

ABSTRACT BACKGROUND: Malignant transformation of endometriosis in the abdominal wall is a rare and still poorly understood event. Less than 30 cases have been reported in the worldwide literature. Most cases of solid tumors are report in a previous abdominal scar with malignant transformation of a focus of endometriosis. Presence of lymph node metastases in nearby chains is frequent and is associated with poor prognosis. CASE REPORT: We report a case of a 42-year-old woman with a history of abdominal surgery (Pfannenstiel) to resect abdominal wall endometriosis. Physical examination revealed a solid mass of approximately 10 cm x 6 cm in the anterior wall of the abdomen. Computed tomography (CT) of the abdomen and pelvis showed a heterogeneous, predominantly hypoattenuating expansive formation measuring 10.6 cm x 4.7 cm x 8.3 cm. The patient underwent exploratory incisional laparotomy, block resection of the abdominal mass and lymphadenectomy of the external and inguinal iliac chains. The abdominal wall was reconstructed using a semi-absorbable tissue-separating screen to reconstitute the defect caused by resection of the tumor. Histological evaluation revealed infiltration by malignant epithelioid neoplasia, thus confirming the immunohistochemical profile of adenocarcinoma with clear cell components. Lymphadenectomy showed metastatic involvement of an external iliac chain lymph node. CONCLUSION: Resection of the mass along with the abdominal wall, with wall margins, is the most effective treatment. Reconstruction is a challenge for surgeons. The patient has been followed up postoperatively for eight months, without any evidence of disease to date.

Endometriosis y carcinoma de celulas claras. Reporte de caso / Endometriosis and clear cell carcinoma. Case report

RESUMEN La endometriosis corresponde a la presencia de glándulas endometriales o estroma en sitios distintos a la cavidad uterina. Afecta del 5 al 15% de las mujeres en edad reproductiva y se asocia a importante sintomatología. La teoría de la menstruación retrógrada propuesta por Sampson es la más aceptada para explicar su etiología. Varios estudios han asociado esta enfermedad a un riesgo aumentado de neoplasia, ésta entidad, denominada endometriosis asociada a malignidad, se localiza en sitios extra gonadales en un 20% de los casos, donde la pared abdominal no alcanza más de 30 casos reportados. Si bien no existe un tratamiento estándar, la mayoría de los autores han adaptado el protocolo de tratamiento para el cáncer de ovario asociado a endometriosis.

ABSTRACT Endometriosis corresponds to the presence of endometrial glands or stroma at sites other than the uterine cavity. It affects 5 to 15% of women of reproductive age and is associated with a significant symptomatology. The theory of retrograde menstruation proposed by Sampson is the most accepted to explain its etiology. Several studies have associated this disease with an increase in neoplasia, the entity, called endometriosis associated with malignancy, is located in extra gonadal sites in 20% of cases, where the abdominal wall does not reach more than 30 reported cases. Although there is no standard treatment, most authors have adapted the treatment for ovarian cancer associated with endometriosis.