Minimal uterine serous carcinoma and endometrial polyp: a close clinicopathological relationship.

Frequently involving an endometrial polyp, minimal uterine serous carcinoma (MUSC) represents the earliest recognizable forms of endometrial serous carcinoma. The aim of this study was to provide a comprehensive morphological and clinical outcome assessment of MUSC involving endometrial polyp. A total of 77 fully staged MUSCs involving endometrial polyp were identified, including 53 MUSCs confined to polyp and 24 nonpolyp confined tumors. Extrauterine disease was found in 17% (9/53) of polyp-confined MUSCs compared to 41.7% (10/24) of nonpolyp confined tumors (p = 0.02). Lymphovascular invasion was observed in 3.8% (2/53) of polyp-confined cases compared to 25% (6/24) of nonpolyp confined cases (p = 0.047). Lymph node metastasis was observed in 11.3% (6/53) of polyp-confined cases, compared to 29.2% (7/24) of nonpolyp confined cases (p = 0.058). Positive pelvic washing cytology was seen in 18.9% (10/53) of polyp-confined versus 37.5% (9/24) of nonpolyp confined tumors (p = 0.078). Overall, 58 of 77 (75.3%) patients had low tumor stage (57 stage I cases and 1 stage II case) and only two patients (3.5%) had a recurrence. In contrast, 19 of 77 (24.7%) patients had advanced stage (stage III or IV) disease and 17 (89.5%) patients had recurrence (p < 0.0001). Only one of 57 low-stage patient (1.7%) versus 11 of 19 high-stage patients (57.8%) died of the tumor (p < 0.0001). Five of 53 (9.4%) patients with polyp-confined MUSC and 7 of 24 (29.2%) patients with nonpolyp confined MUSC died of the disease (p = 0.03). In conclusion, while a small percentage of MUSCs exist without the involvement of an endometrial polyp, a close topographic relationship between MUSC and the endometrial polyp is confirmed in this largest series, supporting the theory that most if not all MUSCs arise in an EMP. Patients with MUSC without extrauterine spread have an excellent prognosis. Compared to patients with MUSC confined to an endometrial polyp, patients with MUSC extending to the background endometrium have a significantly higher risk for high-stage disease at presentation.

Cytoplasmic vacuolization: an under-recognized cytomorphologic feature in endocrine tumors of the pancreas.

The diagnosis of pancreatic endocrine neoplasm (PEN) is often straightforward; however, cytomorphologic variants may impose a diagnostic challenge, particularly in small biopsies such as fine-needle aspiration (FNA). Here we describe prominent fine cytoplasmic vacuoles in three cases of PENs which were initially evaluated by endoscopic ultrasound-guided FNA. The clinicopathologic features and diagnostic pitfalls of this cytomorphologic variant were discussed. Awareness of this rare cytomorphologic feature with application of immunocytochemical studies is crucial for rendering an accurate diagnosis and avoiding diagnostic pitfalls.

BRAFV600E mutation in papillary thyroid microcarcinoma: a genotype-phenotype correlation.

BRAF(V600E) mutation has emerged as a marker of aggressive behavior in papillary thyroid carcinoma but its significance in microcarcinoma is not entirely clear. One-hundred and twenty-nine papillary thyroid microcarcinomas were tested for BRAF(V600E) mutation by single-strand conformation polymorphism, and their clinicopathologic features (age, sex, tumor size, multifocality, nodal metastases, histologic subtype, tumor cell morphology, architecture, tumor-associated stromal reaction, tumor interface to non-neoplastic thyroid (well circumscribed vs infiltrative), extrathyroidal extension, lymphovascular invasion, intratumoral multinucleated giant cells, and adjacent non-neoplastic thyroid pathology) were examined. Compared with tumors without the mutation (39/129, 30%), the mutated microcarcinomas (90/129, 70%) showed significantly higher prevalence of infiltrative tumor borders (78/90 vs 23/39, P=0.001), tumor-associated stromal desmoplasia/fibrosis and/or sclerosis (80/90 vs 25/39, P=0.002), classic nuclear features of papillary thyroid carcinoma (90/90 vs 35/39, P=0.008) and cystic change (43/90 vs 11/39, P=0.05). BRAF(V600E) mutation was more frequent in classic (75%), tall cell (91%), and other variants (>70%) than in follicular variant (21%) of papillary thyroid microcarcinoma. Tumors without the mutation were significantly more likely to be solid, well circumscribed, and lacked desmoplasia/fibrosis or sclerosis. However, on multivariate analysis, only the follicular variant of papillary microcarcinoma was significantly associated with the absence of mutation (odds ratio (95% confidence interval): 0.09 (0.01-0.54)). Lymph node metastases (n=24) were more frequent in microcarcinomas with mutation than without (21/24 vs 3/24, P=0.02). All patients with lateral cervical node metastasis (n=9), and all but one tumor with extrathyroidal extension (n=17/18) showed BRAF(V600E) mutation. No significant differences were noted in age, sex, tumor size, multifocality, lymphovascular invasion, psammoma bodies, stromal calcification, intratumoral multinucleated osteoclastic-type giant cells, and lymphocytic infiltration between the two groups of tumors. BRAF(V600E) mutation is an early event in thyroid carcinogenesis, and is associated with distinctive morphology and aggressive features even in papillary thyroid microcarcinomas.

The utility of 'low-grade intraepithelial lesion, cannot exclude high grade' diagnosis: a single institution's experience.

OBJECTIVE: Squamous intraepithelial lesions (SILs) are classified as low-grade SIL (LGSIL) and high-grade SIL (HGSIL). 'LGSIL cannot exclude high grade' (LGSIL-H) interpretive category has been used in cases where findings exceed criteria for LGSIL, but do not fulfill the criteria for HGSIL. This study analyzed follow-up histology of LGSIL-H cases and compared the follow-up results of LGSIL-H with LGSIL to determine the utility of LGSIL-H category using a single institution's experience. STUDY DESIGN: Pap smears with LGSIL-H interpretation from 2005 to 2008 were retrieved. Histological follow-up results for LGSIL-H cases were analyzed and compared to the follow-up results of LGSIL cases. RESULTS: Cases with LGSIL-H interpretation (311) comprised 0.18% of all cases (170,307). Follow-up was available for 144 patients and 13.2% had benign findings, 51.4% had cervical intraepithelial neoplasia (CIN) 1, and 35.4% had CIN 2 or higher. In comparison, of 425 patients with LGSIL, 22.6% had benign findings, 71% had CIN 1 and 6.4% had CIN 2 or higher. CONCLUSION: A significantly greater number of patients with LGSIL-H interpretation had a CIN 2 or higher lesion on follow-up compared to patients with LGSIL. This suggests LGSIL-H may be a useful diagnostic category.

Addenda in pathology reports: trends and their implications.

Addenda are typically used to report results of additional studies that are delayed relative to histopathologic studies. However, the frequency and pattern of use of addenda have not been previously reported. We studied the dynamics of addenda creation within the same month at 5-year intervals during a 15-year period at our institution. The number of addenda and type and impact of information communicated in addenda were assessed in the month of July in 1993, 1998, 2003, and 2008, and the possible role of addenda in quality improvement was evaluated. Cases with addenda increased from 0.9% in 1993 to 8.6% in 2008. In 5.6% of addenda, there was information that might have been better reported in an amendment, suggesting that criteria for amendments need to be universally implemented. Charting trends and types of addenda offered opportunities for quality improvement by identifying weaknesses in the workflow organization of the laboratory.

Papillary thyroid carcinomas with and without BRAF V600E mutations are morphologically distinct.

AIMS: The BRAF V600E mutation resulting in the production of an abnormal BRAF protein has emerged as the most frequent genetic alteration in papillary thyroid carcinomas (PTCs). This study was aimed at identifying distinctive features in tumours with and without the mutation. METHODS AND RESULTS: Thirty-four mutation-positive and 22 mutation-negative tumours were identified by single-strand conformation polymorphism of the amplified BRAF V600E region in the tumour DNA. Mutation-positive tumours were more common in patients older than 45 years (24/33, P = 0.05), in classic (23/30, P = 0.01), tall cell (4/5) and oncocytic/Warthin-like (2/2) variants of PTC, and in subcapsular sclerosing microcarcinomas (4/4). In contrast, all 12 follicular variants (P < 0.0001) and two diffuse sclerosing variants were negative for the mutation. Mutation-positive tumours displayed infiltrative growth (32/34, P = 0.02), stromal fibrosis (33/34, P < 0.001), psammoma bodies (17/34, P = 0.05), plump eosinophilic tumour cells (22/34, P = 0.01), and classic fully developed nuclear features of PTC (33/34, P = 0.0001). Encapsulation was significantly associated with mutation-negative tumours (15/22, P = 0.02). CONCLUSIONS: BRAF V600E mutation-positive and negative PTCs are morphologically different. Recognition of their morphology may help in the selection of appropriate tumours for genetic testing.

Immunohistochemical techniques to compare primary vs. metastatic mucinous carcinoma of the skin.

BACKGROUND: Primary and metastatic mucinous carcinomas in skin are histologically indistinguishable. Immunohistochemical panels help differentiate primary and metastatic adenocarcinoma of skin, but data regarding mucinous carcinoma is scant. METHODS: We stained five primary mucinous carcinomas, two mucinous carcinomas metastatic to skin and five primary breast and colon mucinous carcinomas with p63, CD15, CK5/6, CK7, CK20, calponin and D2-40 to identify patterns that might differentiate primary from metastatic disease. We also searched for myoepithelial cells in all cases. RESULTS: All cases of primary mucinous carcinoma of the skin were positive for CK7, 40% showed rare cells labeled for p63 and 20% of cases labeled focally for CK5/6. The breast mucinous carcinomas metastatic to the skin were negative for all markers except CK7, although 60% of primary breast carcinomas labeled for p63. Colon mucinous carcinoma labeled only for CK20. CONCLUSIONS: In a small subset of mucinous carcinomas (20% in this series), positive labeling for CK5/6 indicated primary cutaneous tumor. Staining with p63 also favored primary over metastatic disease. Myoepithelial cell layers were not consistently identified to enable the identification of primary disease.