Distinct Histomorphologic Features Research Articles

Histopathologic Characterization of Bladder Perivascular Epithelioid Cell Neoplasms (PEComa): A Series of 11 Cases With a Subset Having TFE3 Rearrangements.

Perivascular epithelioid cell neoplasms (PEComas) of the bladder are extremely rare, with ~30 case reports. A subset of PEComas contain TFE3 gene rearrangement, however, the distinct histomorphologic features of these translocation tumors has not been fully explored in bladder PEComas. In our series, 11 cases of bladder PEComas were collected, including 1 internal and 10 consults, with 1 case previously reported. There was a female predominance (9 female, 2 male) with a mean age of 44.2 years (24 to 61 y). In only 1 of the 10 consult cases was PEComa considered in the differential diagnosis. In 10 of 11 cases, prominent epithelioid features were noted, with the final case having focal epithelioid morphology. Mitotic rate was increased in 2 of 11 cases, and 2 of 11 cases had cytological atypia. Two cases were malignant, with invasion into perivesicle tissue in 1 case, and metastases to lungs and brain followed by death in the other case. Immunohistochemically, there was strong, and diffuse staining for cathepsin K in 10/11 cases with the 1 negative case restained on a previously stained slide. HMB-45 was diffusely positive in 8/11 cases, while melan-A was present in only 1/10 cases. Muscle markers were variably expressed with positivity for both smooth muscle actin in 6/10 cases and desmin in 3/10 cases. Keratin AE1/3 was uniformly negative (0/11). In 5/8 cases where TFE3 was rearranged by fluorescence in situ hybridization, the morphology had a predominantly epithelioid, nested architecture. Overall, bladder PEComas are particularly difficult to diagnose given their rarity, are predominantly epithelioid and do not always express melanocytic markers. Diagnosis in the bladder requires a combination of morphologic characterization, exclusion of other diagnostic possibilities, positive Cathepsin K staining, variable melanocytic marker expression, with some cases showing a TFE3 gene rearrangement.

Revisiting the distinct histomorphologic features of inflammatory bowel disease–associated neoplastic precursor lesions in the SCENIC and post–DALM Era

Distinct histomorphologic features of colitis-associated dysplasia (CAD) or neoplastic precursors in inflammatory bowel disease (IBD) have never been clearly identified. In this study, we tried to further explore the differentiating morphologic features of CAD by retrospectively reviewing the lesions that were clearly associated with carcinomas (carcinoma-related lesions) and by comparing between endoscopically nonpolypoid (non-adenoma-like) lesions and polypoid (adenoma-like) lesions and sporadic conventional adenomas found in the noncolitic mucosa and in patients without IBD. Our study results have revealed that (1) precursor lesions related to IBD-associated colorectal carcinomas were almost always nonpolypoid in macroscopic/endoscopic appearance; (2) nearly half of the carcinoma-related lesions and nonpolypoid lesions were similarly nonadenomatous (nonconventional) lesions, largely serrated type, with no or only mild/focal adenomatous dysplasia, and commonly had mixed adenomatous and nonadenomatous features; (3) carcinoma-related and nonpolypoid adenomatous dysplastic lesions frequently showed some peculiar histocytologic features that we observed and described for the first time, including mixed features of inflammatory pseudopolyps or granulation tissue, pleomorphic and disarrayed nuclei, micropapillary or hobnailing surface epithelial cells, and microvesicular or bubbling cytoplasm of dysplastic cells; and (4) polypoid lesions in the colitic mucosa were identical to sporadic adenomas in the noninflamed mucosa and in patients without IBD, and they lacked the aforementioned features. The seemingly distinctive morphologic characteristics that we proposed here, although still not absolutely specific or unique, can be used as the features of inclusion for identifying CAD on endoscopic biopsies when the endoscopy images are not readily available to pathologistsand thus to alert clinicians for a closer follow-up.

Exploration of BRAFV600E as a diagnostic adjuvant in the non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)

The non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) are distinguished from classical papillary thyroid carcinoma with predominantly follicular architecture (CPTCPFA) by distinct histomorphologic and molecular features. CPTCPFA frequently harbor the oncogenic variant BRAFV600E while NIFTP and EFVPTC are largely RAS driven. CPTCPFA have rare papillae and intranuclear pseudoinclusions that may distinguish them from NIFTP or EFVPTC. We evaluated for BRAFV600E mutation using mutation-specific BRAF (VE1) antibody immunohistochemistry (BRAFVE) as part of an immunomorphologic tumor panel, often including HBME1, for follicular-patterned lesions with nuclear atypia. An archival search identified cases of NIFTP, CPTCPFA, or EFVPTC between 2015-2017, and demographic data, tumor characteristics, molecular data, and metastases were documented. Our search yielded 275 tumors across categories, and 208 were tested with BRAFVE. Sixty-one NIFTP and 31 sub-centimeter NIFTP were tested, and none (0/92) were positive for BRAFVE. Nineteen CPTCPFA and 14 sub-centimeter CPTCPFA were tested with 18 of 33 (54.5%) BRAFVE positive. Sixty-one EFVPTC and 21 sub-centimeter EFVPTC were tested, with 12 of 81 (14.8%) positive. Mean follow-up time was 1.5 years. Six (4.6%) patients with concurrent classical papillary thyroid carcinoma had local lymph node metastases at time of NIFTP diagnosis, as did 15 of 111 (13.5%) EFVPTC. Six of 34 (14.7%) CPTCPFA had local nodal metastases with five being considered the primary lesion. One EFVPTC (0.9%), BRAFVE negative, metastasized to femur. The findings indicate that BRAFVE used in conjunction with routine sampling of follicular-patterned tumors is a useful diagnostic adjuvant.

Improving classification of melanocytic nevi: Association of BRAF V600E expression with distinct histomorphologic features

A subset of melanomas carrying a B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E mutation, which is the most common targetable mutation in melanoma, arise in association with a melanocytic nevus that is also harboring a BRAF V600E mutation. The detailed histomorphologic characteristics of nevi positive for BRAF V600E have not been systematically documented. To identify histomorphologic features correlating with BRAF V600E status in nevi. We retrospectively identified melanocytic nevi from our laboratory reporting system. We performed a histomorphologic analysis and analysis of BRAF V600E expression by immunohistochemistry. Thirteen nevi (14.8%) were negative and 76 (86.4%) were positive for BRAF V600E. The nevi positive for BRAF V600E were predominantly dermal (predominantly dermal growth in 55.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P=.01]) and showed a congenital growth pattern (congenital growth pattern in 51.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P=.02]). Compared with nevi negative for BRAF V600E, those that were positive for BRAF V600E often exhibited predominantly nested intraepidermal melanocytes, larger junctional nests, abrupt lateral circumscription, and larger cell size. Architectural disorder and inflammatory infiltrates were seen more often in nevi negative for BRAF V600E. BRAF sequencing of a subset of nevi confirmed the immunohistochemical results. Limitations include the study's retrospective design and the small sample size of nevi negative for BRAF V600E. BRAF V600E is associated with distinct histomorphologic features in nevi. These features may contribute to improving the accuracy of classification and diagnosis of melanocytic neoplasms.

Immunohistochemistry Applied to the Differential Diagnosis Between Ductal and Lobular Carcinoma of the Breast

The distinction between classic lobular and ductal carcinoma, both in situ and invasive, has important therapeutic and management implications. Most ductal and lobular carcinomas are distinguished readily on hematoxylin-eosin-stained sections because of distinct histomorphologic features. In cases with ambiguous morphologic features, however, categorization in one or another type can be a challenge. Several immunohistochemical markers, including epithelial cadherin, p120, β-catenin, and low-molecular-weight and high-molecular-weight cytokeratins among others, have been introduced to help better discriminate between lobular neoplasia and ductal carcinoma. In this critical review of the literature, we comment about the usefulness and the limitations of these markers to improve the accuracy in the differential diagnosis of breast pathology.

Invasive lobular carcinoma with extracellular mucin as a distinct variant of lobular carcinoma: a case report

The differences between invasive lobular and ductal carcinomas affect the diagnostic and therapeutic management for patients with breast cancer. In most cases, this can be accomplished because of distinct histomorphologic features. However, occasionally, this task may become quite difficult, in particular when dealing with the variants of infiltrating lobular carcinoma. Lobular carcinoma has been considered a variant of mucin-secreting carcinoma with only intracytoplasmic mucin. The presence of extracellular mucin is a feature of ductal carcinoma. Herein is presented a case of lobular carcinoma with extracellular and intracellular mucin in a 43-year-old female patient, and confirmed by immunohistochemistry. Up to the present, infiltrating lobular carcinoma displaying extracellular mucin has not been described in the literature except two case.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1839906067716744

Two cutaneous malignant melanomas at the same anatomic site: a case report with molecular evaluation

Patients who have had malignant melanoma are at an increased risk of developing a second primary melanoma compared with the general population risk of developing a first melanoma. Many of these second primary melanomas occur at a similar anatomic site as the first lesion. Determining whether a second lesion is indeed a separate primary vs. a metastasis or locoregional recurrence can be very difficult histologically. We report the case of a patient who developed a second melanoma, 2 years after the initial diagnosis, within 3 cm of the site of the original lesion. Because of distinct histomorphologic features, the second lesion was favored to be a separate primary. However, because of the nearly identical anatomic location, molecular testing for loss of heterozygosity and BRAF mutation was performed to help further make this distinction. The first lesion was found to have loss of heterozygosity and a BRAF mutation that were not present in the second lesion. While these tests cannot elucidate the true molecular origin of these lesions, they provide a useful clinical tool to assess whether a second lesion should be treated as a recurrence or as a separate lesion with unique biologic potential.

Microsatellite instability in sporadic carcinomas of the proximal colon: Association with diploid DNA content, negative protein expression of p53, and distinct histomorphologic features

Background: Microsatellite instability (MIN) seems to characterize a particular subset of sporadic colorectal adenocarcinomas with the studies indicating a better clinical outcome for patients with MIN-positive tumors than for those with MIN-negative ones. The goal of this study was to further clarify whether a genotype-specific histomorphology of the right-sided colonic carcinomas can be identified. Methods: MIN status, DNA content, and p53 protein expression were evaluated in cryoconserved specimens from 20 adenocarcinomas of the proximal colon and correlated to stage, grade, and other histomorphologic features. The study was restricted to tumors of the proximal colon because approximately 90% of all MIN-positive tumors were found in the proximal colon, and differences between right- and left-sided tumors cannot be excluded a priori. Results: By using four microsatellite markers, instability was detected in 35% of the tumors analyzed. The clinicopathologic features in the MIN-positive tumors were found to differ markedly from the MIN-negative tumors in their poorly differentiated histologic pattern, extracellular mucin production, and favorable lymph node and distant metastatic behavior. A marked association was found between MIN positivity and DNA diploid status, as well as negative p53 immunostaining. Conclusions: The MIN-positive colonic carcinomas were characterized by distinct histomorphologic features that are recognizable at routine diagnostic evaluation. Poorly differentiated adenocarcinomas of the proximal colon, with only a few lymph nodes and no distant metastases at presentation, and lack of p53 accumulation are highly suggestive of being MIN positive. These tumors should be discriminated from the other poorly differentiated carcinomas, because they seem to be associated with an improved prognosis compared with the tumors without microsatellite instability. (Surgery 1998;123:13-8.)

Microsatellite instability in sporadic carcinomas of the proximal colon: Association with diploid DNA content, negative protein expression of p53, and distinct histomorphologic features

Microsatellite instability in sporadic carcinomas of the proximal colon: Association with diploid DNA content, negative protein expression of p53, and distinct histomorphologic features