Simultaneous p53 and KRAS mutation in a high-grade serous carcinoma with deceptive appearance of a low-grade carcinoma. A case report.

Low-grade and high-grade serous carcinomas have unique clinical, morphological, underlying molecular alterations, and vastly different biologic behavior (Prat et al., 2018, Vang et al., 2009). The differentiation into high and low-grade serous carcinoma is important for clinical management and prognosis and is easily recognized by practicing pathologists. High-grade serous carcinoma is characterized by marked nuclear atypia and pleomorphism, frequent, often atypical mitosis with papillary or three-dimensional clusters, p53 mutation, and block-like p16 staining. In contrast, low-grade serous carcinomas have a different morphologic appearance with micropapillary formation, small nests of tumor cells having low to intermediate grade nuclei, and absence of significant mitosis. Low-grade serous carcinoma is often associated with micropapillary variant of ovarian serous borderline tumor. The low-grade serous carcinoma shows wild type p53 expression, patchy p16 staining, and often K-RAS, N-RAS, and/or B-RAF mutation. Here we report a case of mullerian high grade serous with a deceptive morphology resembling low-grade serous carcinoma with micropapillary features and moderate nuclear atypia. However, the tumor is simultaneously p53 and K-RAS mutated. This case illustrates three critical issues; a) potential to be mistaken as a low-grade serous carcinoma because of morphologic appearance and relative uniform cytologic feature. b). raise the question of true progression of low-grade to high-grade serous carcinoma, a rare phenomenon as described in the literature, and c). whether the biologic behavior and/or response to therapy would differ from the classic forms.

Ciliated/tubal-type in-situ and invasive endocervical adenocarcinoma: Report of three cases with limited follow-up and review of the literature.

In situ (AIS) and invasive endocervical adenocarcinoma have two broad categories, HPV-associated (HPV) and HPV-independent groups. (1) These entities show various types of cell morphology. Tubal and tubo-endometrioid type metaplasia of the cervix is a benign finding (Suh and Silverberg, 1990). Tubal metaplasia is also encountered in benign and malignant endometrial lesions. During cervical biopsy interpretations, differentiating the site of origin of the tissue is often tricky. We intend to document three cases of the sparsely reported hrHPV-associated ciliated/tubal-type endocervical AIS and invasive adenocarcinoma and bring it to the attention of readers how to avoid any misinterpretation during routine sign-out. Only three of fifty-three cases of hrHPV-associated AIS and invasive adenocarcinoma were of ciliated/tubal type in our department over a 5-year time. The presence of tubal-type epithelium should not automatically trigger the assumption of endometrial origin of the lesion. These cases are red herrings as tubal/ciliated type dysplasia, and carcinoma is rare and have potential to escape accurate diagnosis.

IgG4 Aortitis: A Case Report.

IgG4 aortitis is one of the entities seen in the spectrum of IgG4-related disease (IgG4-RD). It is characterized by serologic (elevated serum IgG4) and histologic features including a lymphoplasmacytic infiltrate with increased numbers of IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. Some studies have described a correlation between infections and IgG4 aortitis. We describe a patient with an aneurysm of the infrarenal descending abdominal aorta with features of IgG4-RD, as well as culture evidence of Streptococcus sanguis. [Full article available at http://rimed.org/rimedicaljournal-2017-04.asp].

TGR5 expression in benign, preneoplastic and neoplastic lesions of Barrett's esophagus: Case series and findings.

AIM: To examined the bile acid receptor TGR5 expression in squamous mucosa, Barrett's mucosa, dysplasia and esophageal adenocarcinoma (EA). METHODS: Slides were stained with TGR5 antibody. The staining intensity was scored as 1+, 2+ and 3+. The extent of staining (percentage of cells staining) was scored as follows: 1+, 1%-10%, 2+, 11%-50%, 3+, 51%-100%. A combined score of intensity and extent was calculated and categorized as negative, weak, moderate and strong staining. TGR5 mRNA was measured by real time PCR. RESULTS: We found that levels of TGR5 mRNA were significantly increased in Barrett's dysplastic cell line CP-D and EA cell line SK-GT-4, when compared with Barrett's cell line CP-A. Moderate to strong TGR5 staining was significantly higher in high-grade dysplasia and EA cases than in Barrett's esophagus (BE) or in low-grade dysplasia. Moderate to strong staining was slightly higher in low-grade dysplasia than in BE mucosa, but there is no statistical significance. TGR5 staining had no significant difference between high-grade dysplasia and EA. In addition, TGR5 staining intensity was not associated with the clinical stage, the pathological stage and the status of lymph node metastasis. CONCLUSION: We conclude that TGR5 immunostaining was much stronger in high-grade dysplasia and EA than in BE mucosa or low-grade dysplasia and that its staining intensity was not associated with the clinical stage, the pathological stage and the status of lymph node metastasis. TGR5 might be a potential marker for the progression from BE to high-grade dysplasia and EA.

Comparison of estrogen receptor, progesterone receptor and HER2 results in concurrent ipsilateral samples with invasive breast carcinoma: a retrospective study of 246 biopsies from 119 patients.

There is no consensus regarding biomarker testing on the ipsilateral breast carcinomas present in separate biopsies, irrespective of whether the biopsies are performed concurrently or consecutively. We aimed to investigate estrogen receptor (ER), progesterone receptor (PR) and HER2 concordance in ipsilateral concurrent biopsies with invasive breast tumors. Consecutive ipsilateral concurrent biopsies with invasive breast tumors were identified retrospectively. Biomarker results, histologic grade and histologic subtype among the tumors in concurrent samples were compared. ER, PR, and HER2 expression was different in 3 (2.5%), 11 (9.2%) and 7 (5.9%) cases, respectively. All ER-discordant cases were sets of ER-negative (ER-) and weak-low ER-positive (ER+), ductal subtype and histologic grade 2 or 3 tumors. All PR-discordant cases were ER+, and comprised of histologic grades 1 to 3 ductal as well as lobular tumors. All HER2 discordant cases were histologic grade 2 to 3 ductal tumors. Biomarker discordance was independent of grade and subtype discordance. We found very low biomarker discordance among tumors in concurrent samples from ipsilateral breast. Our results suggest that ER and HER2 discordance in concurrent samples is predictable. ER discordance is present only in a setting of low ER+ tumors. Low-grade ductal and/or lobular tumors are ER and HER2 concordant. HER2 discordance is noted in grade 2 to 3 ductal tumors only. Histologic subtype and grade may guide extent of biomarker testing in concurrent ipsilateral breast biopsies.