Apath (United States)

Endometriumun müsinöz proliferasyonu, serviksin müsinöz adenokarsinomu ve mikroglandüler proliferasyonu ile karışabilen bir endometrial mikroglandüler adenokarsinom vakası sunduk. 54 yaşında postmenopozal kadın hasta vajinal kanama ile başvurdu. Histolojik olarak endometrial küretaj, küboidal ve kolumnar hücrelerle döşeli, sıkı paketlenmiş mikroglandüler ve müsinöz glandüler alanlarla karakterizeydi. Mikroglandüler lümenlerde ve stromada çok sayıda nötrofil mevcuttu. İmmünohistokimyasal olarak, Vimentin, CEA, Östrojen ve Progesteron reseptörleri ile fokal pozitivite izlendi. Histolojisi serviksin mikroglandüler hiperplazisine benzeyen endometrial mikroglandüler adenokarsinoma benzerliği yönüyle malignensi açısından şüpheliydi. Ardından gelen histerektomi spesmeninde, miyometrial invazyon göstermeyen yüzeyel bir mikroglandüler adenokarsinom belirlendi. Çok sayıda tubal, eozinofilik sinsityal ve skuamöz metaplazi alanları izlendi. Böyle şüpheli neoplazmların doğru patolojik tanısı için patologların klinik bilgi, morfolojik inceleme ve immünohistokimyasal destek konusunda dikkatli olmaları gerekmektedir. We report a case of endometrial microglandular adenocarcinoma which can be confused with microglandular hyperplasia and mucinous adenocarcinoma of the cervix and mucinous proliferation of the endometrium. A 54-year-old postmenopausal woman presented with vaginal bleeding. Histologically, endometrial biopsy was characterized by closely packed microglandular and mucinous glandular areas, which is lined by cuboidal and columnar cells. There was a multitude of neutrophils in microglandular lumens and stroma. Immunohistochemically, focal positivity for vimentin, CEA, estrogen and progesterone receptors were seen. The histology was suspicious for malignancy that might be compatible with microglandular adenocarcinoma of the endometrium resembling microglandular hyperplasia of the cervix. In the final workout of the hysterectomy specimen, we determined a superficial microglandular adenocarcinoma with no myometrial invasion. Several tubal, eosinophilic syncytial and squamous metaplasia areas were present. Pathologists require sufficient clinical information, morphologic experience and immunohistochemical assistance to make the correct pathological diagnosis in such confounding neoplasms.

Insulinomas are pancreatic islet tumors that inappropriately secrete insulin, producing hypoglycemia. Exome and targeted sequencing revealed that 14 of 43 insulinomas harbored the identical somatic mutation in the DNA-binding zinc finger of the transcription factor Yin Yang 1 (YY1). Chromatin immunoprecipitation sequencing (ChIP-Seq) showed that this T372R substitution changes the DNA motif bound by YY1. Global analysis of gene expression demonstrated distinct clustering of tumors with and without YY1(T372R) mutations. Genes showing large increases in expression in YY1(T372R) tumors included ADCY1 (an adenylyl cyclase) and CACNA2D2 (a Ca(2+) channel); both are expressed at very low levels in normal β-cells and show mutation-specific YY1 binding sites. Both gene products are involved in key pathways regulating insulin secretion. Expression of these genes in rat INS-1 cells demonstrated markedly increased insulin secretion. These findings indicate that YY1(T372R) mutations are neomorphic, resulting in constitutive activation of cAMP and Ca(2+) signaling pathways involved in insulin secretion.

Objective: Nowadays, sentinel lymph node (SLN) biopsy is a standard approach giving information about status of the axillary lymph nodes. Several factors affect metastasis to SLN. In our case, we aimed to indicate histopathological parameters that affect SLN and non-sentinel lymph node (n-SLN) metastasis, the importance of frozen section to determine metastasis and immunohistochemistry method for histopathological examinations. Material and Methods: In Uludag University Faculty of Medicine, 265 cases who had SLN biopsies were retrospectively examined. Frozen sections, permanent sections and sections with immunohistochemistry were found out from the archieve. Then, preparations were re-examined by expert pathologists on breast pathology. Results: The mean age of the cases was 53 years. The most frequently observed tumor type was invasive ductal carcinoma. Most of the cases had nuclear grade 2. One hundred cases are diagnosed as malignant. As a result of implementation of serial sections and immunohistochemistry to 12 cases without metastasis, macro-metastasis in four cases, micro-metastasis in six cases and finally isolated tumour cells in two cases were determined. In primary breast tumor, the presence of venous/vascular invasion (p= 0.021), lymphatic invasion (p< 0.001), increased primary tumor diameter (p= 0.001) and increased age (p= 0.026) increased SLN metastasis. In primary breast tumor, the presence of perineural invasion (p= 0.033) and lymphatic invasion (p= 0.045), increased tumor diameter (p= 0.001), and increased number of positive SLNs (p= 0.015) caused an increase in n-SLN metastasis. Conclusion: SLN biopsy is a simple and reliable method. In our study, we found statistically significant results between SLN metastasis and age, primary tumor diameter, lymphatic invasion and venous/vascular invasion. Besides, statistically significant relationships were found between n-SLN metastasis and primary tumor diameter, perineural invasion and lymphatic invasion as well. Intraoperative analysis of SLN is very important for staging of breast carcinoma and prognosis. Moreover, accuracy of diagnosis increases with the applications of serial section and immunohistochemical method.

Tumor to tumor metastasis is a well-known but a rare event. Lung carcinoma, being as a donor and renal cell carcinoma (RCC) serving as a recipient tumor are the most commonly observed tumor to tumor metastatis. Renal cell carcinoma serving as recipient of metastatic breast carcinoma is very rare, and to our knowledge only four cases including three autopsy cases have been reported to date. Herein, we report a case of a 69-year-old woman with invasive lobular carcinoma of the breast that metastased to RCC and internal genital organs including right ovary, uterus and as well as to a benign tumor, lipoleiomyoma.

The nonclassical MHC class I-related (MHC-I) molecule HFE controls cellular iron homeostasis by a mechanism that has not been fully elucidated. We examined the regulation of HFE by K5, the E3 ubiquitin ligase encoded by Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8), that is known to down-regulate classical MHC-I. K5 down-regulated HFE efficiently, using polyubiquitination of the membrane proximal lysine in the HFE cytoplasmic tail (K331), to target the molecule for degradation via ESCRT1/TSG101-dependent sorting from endosomes to multivesicular bodies (MVBs)/lysosomes. In the primary effusion lymphoma cell line BC-3, which carries latent KSHV, HFE was degraded rapidly upon virus reactivation. HFE was ubiquitinated on lysine-331 in unactivated BC-3 cells, conditions where K5 was not detectable, consistent with an endogenous E3 ubiquitin ligase controlling HFE expression. The results show regulated expression of HFE by ubiquitination, consistent with a role in cellular iron homeostasis, a molecular mechanism targeted by KSHV to achieve a positive iron balance.