Westerhoff, Maria

Kaposi sarcoma (KS) can pose diagnostic challenges in biopsy specimens. Multiple histologic variants of cutaneous KS have been described; however, the histomorphologic spectrum of gastrointestinal (GI) KS has not been systematically studied. This large series comprehensively evaluated 46 cases of KS involving the GI tract and identified 7 histomorphologic variants, some that have not been previously described. Five of them are inconspicuous but have unique morphologic patterns, including lymphangioma/lymphangiectatic–like (n=17), mucosal hemorrhage/telangiectatic–like (n=17), mucosal inflammation–like (n=15), granulation tissue–like (n=13), and mucosal prolapse–like (n=4) variants. These variants can be easily misdiagnosed or misinterpreted on routine examination if KS is not considered, and if the immunohistochemical stain for human herpesvirus-8 is not performed. The other 2 morphologic variants present as spindle cell proliferations and are the GI stromal tumor–like (n=8) and inflammatory myofibroblastic tumor–like (n=2). These variants raise a broad differential diagnosis of spindle cell tumors of the GI tract and could pose diagnostic challenges. In summary, GI KS lesions exhibit variable, often unconventional histomorphologic patterns. KS should be included in the differential diagnosis even if features of conventional KS are not seen, particularly in limited biopsies in immunocompromised patients, such as those with human immunodeficiency virus infection. Although the clinical significance of these morphologic variants is yet to be determined, they are nonetheless important from a diagnostic standpoint. Misdiagnosis and delay in appropriate management can be avoided by recognizing the morphologic diversity of GI KS and appropriately utilizing the human herpesvirus-8 immunohistochemical stain.

Abstract Background and Aims Several different types of non-conventional dysplasia have been recently described in inflammatory bowel disease [IBD]. Hypermucinous, goblet cell-deficient and crypt cell dysplasias have received most attention, but there is limited information regarding their clinicopathological features and clinical outcomes. Methods A total of 126 cases of hypermucinous [n = 55], goblet cell-deficient [n = 26] and crypt cell [n = 45] dysplasias from 97 IBD patients were collected from seven different institutions and analysed. Results The cohort included 62 [64%] men and 35 [36%] women with a mean age of 49 years [range: 20–78]. The majority of affected patients had longstanding IBD [mean duration: 18 years]. Nineteen [20%] patients had a concurrent history of primary sclerosing cholangitis. As a group, non-conventional dysplasia was predominantly found in patients with ulcerative colitis [UC] [n = 68; 70%] and occurred in the left colon [n = 80; 63%]; however, hypermucinous dysplasia [57%] was the least frequently associated with UC compared with goblet cell-deficient [74%] and crypt cell [89%] dysplasias [p = 0.016]. Fifty [52%] patients had a history of conventional dysplasia, detected in the same colonic segment as non-conventional dysplasia at a rate of 33%. Goblet cell-deficient dysplasia [74%] was more frequently associated with conventional dysplasia than hypermucinous [43%] and crypt cell [48%] dysplasias [p = 0.044]. While hypermucinous dysplasia often had a polypoid appearance [58%], crypt cell [96%] and goblet cell-deficient [65%] dysplasias were more likely to present as flat/invisible lesions [p < 0.001]. Most lesions were low-grade [87%] at diagnosis, but goblet cell-deficient dysplasia [31%] more often showed high-grade dysplasia [HGD] compared with hypermucinous [15%] and crypt cell [0%] dysplasias [p = 0.003]. Hypermucinous dysplasia usually demonstrated a tubulovillous/villous architecture [76%], whereas goblet cell-deficient dysplasia was predominantly tubular [92%]. A flat architecture was exclusively associated with crypt cell dysplasia [100%] [p < 0.001]. Immunohistochemical stain results for p53 were available for 33 lesions; 14 [42%] showed strong [3+] and patchy [10–50%] to diffuse [>50%] nuclear overexpression or null staining pattern, including four [33%] of 12 hypermucinous, two [29%] of seven goblet cell-deficient and eight [57%] of 14 crypt cell dysplastic lesions [p = 0.726]. Follow-up biopsies or resections were available for 92 low-grade lesions from 71 patients; 55 [60%] lesions, including 19 [49%] of 39 hypermucinous, 10 [59%] of 17 goblet cell-deficient and 26 [72%] of 36 crypt cell dysplastic lesions [p = 0.116], were associated with subsequent detection of HGD [n = 34; 37%] or adenocarcinoma [n = 21; 23%] at the site of previous biopsy or in the same colonic segment within a mean follow-up time of 12 months [range: <1–73]. Conclusions Hypermucinous, goblet cell-deficient and crypt cell dysplasias have distinct clinicopathological features but appear to have a similar high risk of association with advanced neoplasia [HGD or adenocarcinoma]. More than half of the lesions [66%] presented as flat/invisible dysplasia, suggesting that IBD patients may benefit from random biopsy sampling in addition to targeted biopsies. Although not uncommonly associated with conventional dysplasia, non-conventional dysplasia may be the only dysplastic subtype identified in IBD patients. Therefore, it is important to recognize these non-conventional subtypes and recommend complete removal and/or careful examination and follow-up.

AimsThe diagnosis of focal nodular hyperplasia (FNH) and the interpretation of glutamine synthetase (GS) staining can be challenging on biopsies. We aimed to evaluate the reproducibility of needle biopsy diagnosis of FNH, the effect of GS immunohistochemistry on FNH diagnosis, and which histological features are most useful for the diagnosis of FNH.Methods and resultsThe study included virtual needle biopsies generated from 75 resection specimens (30 FNHs, 15 hepatocellular adenomas, 15 hepatocellular carcinomas, and 15 non‐lesional liver specimens). Pathologists were reasonably accurate (83.1%) in the diagnosis of FNH with haematoxylin and eosin alone. Ductular reaction and nodularity had the highest sensitivity for a diagnosis of FNH (88.1% and 82.2%, respectively), whereas central scar was the most specific feature (90.6%). The presence of two or more of the classic histological features had 89.6% sensitivity and 86.2% specificity for a diagnosis of FNH. Diagnostic accuracy was significantly higher with the addition of a GS stain. A map‐like GS staining pattern was highly specific (99.3%) for FNH. However, GS staining was interpreted as non‐map‐like in 14.4% of reviews of true FNH cases, and overall interobserver agreement for interpretation of the GS staining pattern was only moderate (kappa = 0.42).ConclusionsPathologists are reasonably accurate in the diagnosis of FNH on virtual biopsies, and GS staining improves accuracy. However, a subset of FNH cases remain challenging. Steatosis and a pseudo‐map‐like GS staining pattern were associated with increased difficulty. Therefore, although a map‐like GS staining pattern is useful for confirmation of a diagnosis, the lack of a map‐like GS staining pattern on needle biopsy does not necessarily exclude a diagnosis of FNH.

Abstract Objectives Mucinous cystic neoplasm of the liver is characterized by neoplastic mucinous and/or biliary epithelium surrounded by ovarian-type stroma. Immunohistochemical studies have shown that the ovarian-type stroma expresses estrogen receptor, suggesting potential hormonal responsiveness. The molecular biology of mucinous cystic neoplasm of the liver remains poorly studied. Methods Transcriptome sequencing and immunohistochemistry were performed on a series of mucinous cystic neoplasms. Results Mucinous cystic neoplasm of the liver exhibited significantly increased RNA expression of ovarian stromal markers WT1, PR, and ER2 and sex cord stromal markers SF-1, inhibin-α, and calretinin compared with nonneoplastic liver. Immunohistochemistry confirmed the RNA-level data. Evidence for sex hormone biosynthesis was identified by significant overexpression of multiple estrogen biosynthetic enzymes. Expression of 17β-hydroxysteroid dehydrogenase 1 was confirmed immunohistochemically. Pathway analysis also identified significant upregulation of the hedgehog and Wnt pathways and significant downregulation of T-helper 1 and T-helper 2 pathways. Conclusions Mucinous cystic neoplasm of the liver recapitulates ovarian stroma at the morphologic, DNA, RNA, and protein levels. These data support the concept that this tumor likely arises from ectopic primitive gonadal tissue and/or stromal cells with capacity to transdifferentiate to ovarian cortical cells.