Cistoadenocarcinoma mucinoso retroperitoneal primário em mulher que apresentou recidiva: um raro relato de caso no interior de São Paulo

Objetivo: Colaborar com o número de casos publicados, visto a escassez na literatura mundial e raridade da doença estudada, contribuindo para a propedêutica e futuras metanálises. Detalhamento do caso: Paciente do sexo feminino, 46 anos, apenas hipertensa prévia, deu entrada em hospital terciário pela equipe da cirurgia geral com suspeita de cisto retroperitoneal. Foi submetida a laparotomia e excisão de massa que pesou aproximadamente 2,5 kg na análise realizada pela equipe de patologia. O diagnóstico foi de Cistoadenocarcinoma Mucinoso Retroperitoneal Grau II com imunohistoquímica “Cytokeratin 7” positivo difuso, “Cytokeratin 20” positivo focal, “MUC5AC” positivo, “CDX2” positivo em raras células. Foi submetida a 6 sessões de quimioterapia com Carboplatina e Paclitaxel com queda do marcador CA-125 e boa resposta ao tratamento. No seguimento, após 11 meses, apresentou recidiva com metástase hepática e marcador CA125 elevado, sendo novamente reiniciada a quimioterapia, porém, paciente evoluiu com quadro de insuficiência respiratória evoluindo a óbito no final do ano de 2017. Considerações finais: O PRMCa é um tumor raro e ainda com escassa literatura que nos auxilie acerca dos fatores de risco, estadiamento do tumor e tratamento adequado que diminua a chance de recidivas. Este caso auxiliará diagnósticos e tratamentos futuros.

Cytokeratin 7 and Copper Stains Facilitate Diagnosis of Small Duct Primary Sclerosing Cholangitis

Introduction/Objective Classic primary sclerosing cholangitis (PSC) involves extrahepatic and/or intrahepatic biliary ducts with segmental biliary strictures and dilatations that often allow the diagnosis to be made via cholangiogram. Small duct PSC (sdPSC) is a rare subtype that presents similarly with a cholestatic pattern of injury, yet due to the small size of involved ducts, a cholangiogram is non-diagnostic and diagnosis is dependent on clinical suspicion and liver biopsy. The histopathological features of sdPSC are often subtle and may easily be overlooked. Diagnosis of this entity- though difficult- is important, as early recognition can facilitate the identification of associated disease processes and life-threatening complications. Methods/Case Report We encountered a 33-year-old female presenting with intermittent pruritis, episodes of jaundice, and persistently elevated alkaline phosphatase who was misdiagnosed with only fatty liver at an outside institution. Evaluation with MRCP showed no abnormalities within the biliary tract and a liver biopsy was performed to aid in the diagnosis. The H&E and trichrome findings of atrophic bile ducts and some peribiliary sclerosis were extremely subtle and may have been overlooked without clinical suspicion. Cytokeratin 7 (CK7) highlighted cholangiolar metaplasia in hepatocytes and the bile ductular reaction that occurs in cholestatic disease states. A Rhodamine copper stain showed periportal deposition suggestive of chronic biliary obstruction. Use of CK7 and copper stains supported the presence of chronic biliary injury and suboptimal bile flow, confirming the diagnosis of sdPSC. Results (if a Case Study enter NA) NA Conclusion Diagnosis of sdPSC has historically relied on H&E and trichrome stains. In this case, the findings on H&E and trichrome stains were non-diagnostic, while the use of CK7 and copper stains confirmed the diagnosis of sdPSC. We recommend using CK7 and copper stains to evaluate for sdPSC.

Cytokeratin 7 expression as a predictor of an unfavorable prognosis in colorectal carcinoma

Colorectal carcinoma (CRC) is associated with significant morbidity and mortality worldwide. Cytokeratins (CKs) are widely expressed in various types of carcinomas, whereas in CRC it is usually CK7 − and CK20 + . A subset of CRCs is CK7 + . This study aims to determine the prevalence of CK7 expression in CRC and its impact on overall survival. We analyzed 300 randomly selected surgically treated CRC cases using paraffin embedded tumor tissue samples and evaluated CK7 and CK20 expression using the tissue microarray method. Tumors with positivity > 10% and > 25% of tumor cells were considered CK7 and CK20 positive, respectively. Expression of both CKs and several clinical-pathological variables (stage, grade, laterality, mismatch-repair/MMR status) were evaluated using patient follow up data (Kaplan–Meier analysis of cancer-specific survival (CSS)). Significant results include shorter CSS (restricted mean 4.98 vs. 7.74 years, P = 0.007) and 5-year survival (29.4% vs. 64.6%, P = 0.0221) in CK7 + tumors compared to CK7 − tumors, respectively; without significant association with grade, stage or right-sided location. These results were significant in a multivariate analysis. CK20 + tumors are more frequently MMR-proficient and left-sided. MMR-deficient tumors are more frequently right-sided and had longer survival. CK7 expression, right-sided location (rmean CSS 6.83 vs. 8.0 years, P = 0.043), MMR-proficiency (rmean CSS 7.41 vs. 9.32 years, P = 0.012), and UICC stages III + IV (rmean CSS 6.03 vs. 8.92 years, P < 0.001) of the tumor correlated with negative prognostic outcomes, whereas the most significant results concern stage and CK7 positivity. The result concerning negative prognostic role of CK7 differs from those obtained by several previous studies focused on this topic.

Evaluation of Relationship Between Cytokeratin 7 Expression with Some Prognostic Factors in Gastric and Colorectal Adenocarcinomas

Background: Gastric and colorectal adenocarcinomas are the second and fifth most common cancers in Iran, respectively. Prognostic factors help with the better management of patients. Objectives: The current study aimed to evaluate Cytokeratin 7 (CK7) expression in gastric and colorectal adenocarcinomas and its correlation with other prognostic factors. Methods: This cross-sectional study was performed on 75 tissue blocks from patients with gastric or colorectal adenocarcinomas. Tumor grade, tumor size, depth of invasion, and metastasis to lymph nodes were determined. Then, CK7 expression was studied using immunohistochemistry staining. The presence of CK7 was scored under high power (400x) in 1000 tumor cells, and the percentage of positive immunostaining (5%) was determined. Results: The mean age values of the patients were 62.11 ± 14.13 and 55.23 ± 14.14 years in gastric cancer and colorectal cancer groups. There was no statistically significant difference in the mean tumor size between the two groups (P = 0.678). The findings of the present study showed that in 19 cases (67.9%) of gastric cancer samples, 6 cases (42.9%) of rectal samples, and 14 cases (42.4%) of colon samples were positive for CK7. The expression of positive cytokeratin was higher than that of the rectum and colon, which was statistically significant (P = 0.034). Furthermore, there was no statistically significant relationship between the type of differentiation and lymph node involvement with cytokeratin expression in both gastric and colorectal cancers (P > 0.05). In terms of perineural involvement, there was no statistically significant relationship with both gastric and colorectal cancers (P > 0.05). Conclusions: The present study showed no association between CK7 expression and prognostic factors in colon and gastric adenocarcinomas. Given these findings and several studies in this field, it is required to perform further studies with a larger sample size to determine the exact prognostic role of this factor.

Colon Cancer With Metastatic Involvement of the Thyroid Incidentally Found at Excision of Parathyroid Adenoma

Metastatic disease from primary colon cancer in the thyroid is rare. The authors have submitted such a case. What makes this case particularly unusual is that it was in a man. 80% of such cases are in women. It has been speculated that there may be a humoral component. What is even more unique in this case is that it was found during the workup of a symptomatic parathyroid adenoma. The diagnosis was confirmed with immunochemistry using markers Cytokeratin 20 (CK20), Cytokeratin 7 (CK7), and Thyroid Transcription Factor 1 (TTF-1) .

A submandibular nodule revealing a relapsed bladder urothelial carcinoma

A 69-year-old patient treated for infiltrating bladder transitional carcinoma many years ago presented with a submandibular nodule. The last was fortuitously discovered by the patient a month before he presented to consultation. Physical examination showed a firm subcutaneous nodule of 0.5 cm in diameter in the right submandibular region. At this level skin was inflamed/red and swollen. Otherwise physical examination was within normal. The described nodule above was biopsied. Microscopic examination showed infiltration of the dermis by a carcinomatous proliferation (Fig. 1). Tumor cells were arranged in small nests and clusters surrounded by a fibrous stroma. Tumor cells showed moderate nuclear atypia. Immunohistochemical staining showed positivity of tumor cells for Cytokeratin 7 and P63 (Fig. 2). Therefore, taking into consideration patient’s medical history, microscopic and immunohistochemical findings the diagnosis of CM from urothelial carcinoma was retained. The first case of CM from bladder carcinoma was reported in 1909 [3]. Since then many case have been reported [1,2]. According to cases reported in literature so far, the mean interval of time between the setting of bladder cancer and the appearance of CM is of 18 months approximately. Large tumor size and deep infiltration of the bladder wall are predictive factors of CM. However, cases of CM associated with superficial bladder carcinomas were reported [3]. The certain diagnosis is based on microscopic examination [1,3]. Pathologists should be aware of patient’s medical history to facilitate the diagnosis and choosing appropriate immunostains if necessary especially in front of a poorly differentiated carcinoma[3]. Urothelial carcinomas express Cytokeratin 7 and Cytokeratin 20 antibodies [3]. The occurring of CM in case of bladder cancer darken the prognosis [1,2]. Median survival rates are less than 12 months in published cases so far [1,3]. Treatment consists of chemotherapy if the patient could bare it [1]. Total recovery was detected in 70% of cases of CM treated with chemotherapy. Yet, it does not improve global survival rates [3].

Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn’s disease-associated small bowel carcinoma

Most Crohn’s disease-associated small bowel carcinomas (CrD-SBCs) are diagnosed in advanced stage and have poor prognosis. To improve diagnosis and therapy, a better knowledge of tumour precancerous lesions, histotypes and prognostic factors is needed. We investigated histologically and immunohistochemically 52 CrD-SBCs and 51 small bowel carcinomas unrelated to inflammatory disease, together with their tumour-associated mucosa, looking for Crohn-selective changes. Histologic patterns and phenotypic markers potentially predictive of CrD-SBC histogenesis and prognosis were analysed. Cytokeratin 7 or MUC5AC-positive metaplastic changes were found in about half of investigated CrD-SBCs, significantly more frequently than in CrD-unrelated SBCs. They correlated with metaplastic changes of their associated mucosa, while being absent in normal ileal mucosa. Histologic patterns suggestive for progression of some cytokeratin 7 and/or MUC5AC-positive metaplastic lesions into cancer of the same phenotype were also observed. Patient survival analyses showed that tumour cytokeratin 7 or MUC5AC expression and non-cohesive histotype were adverse prognostic factors at univariable analysis, while cytokeratin 7 and non-cohesive histotype were also found to predict worse survival in stage- and age-inclusive multivariable analyses. Besides conventional dysplasia, hyperplasia-like non-conventional lesions were observed in CrD-SBC-associated mucosa, with patterns suggestive for a histogenetic link with adjacent cancer. In conclusion the cytokeratin 7 and/or MUC5AC-positive metaplastic foci and the non-conventional growths may have a role in cancer histogenesis, while tumour cytokeratin 7 and non-cohesive histotype may also predict poor patient survival. Present findings are worth being considered in future prospective histogenetic and clinical studies.

Thyroid-Like Cholangiocarcinoma: Histopathological, Immunohistochemical, In-Situ Hybridization and Molecular Studies on an Uncommon Emerging Entity

Thyroid-like cholangiocarcinoma is a very uncommon variant of peripheral-type cholangiocarcinoma. To date, only 4 prior cases have been reported. The molecular features of this tumor have not been described. We report a case of a 60-year-old woman with a tumor that evolved over a period of 10 years. A left hepatectomy specimen showed an 11 cm tumor that on histology exhibited areas reminiscent of a thyroid tumor with follicular and insular features which were positive on immunohistochemistry for cytokeratin 7 and in-situ hybridization for albumin. A detailed molecular analysis failed to show mutations common to cholangiocarcinomas but revealed frameshift mutations in 2 chromatin-remodeling genes, CREBBP and KMNT2A. This case confirms that thyroid-like cholangiocarcinoma is a histologic variant of this tumor that is associated with relatively low growth. As most cholangiocarcinomas, it is diffusely positive for cytokeratin 7 and albumin by in-situ hybridization. Given its rarity, the molecular alterations in this specific histologic subtype remain to be fully elucidated.