Synovial Sarcoma of the Gastrointestinal Tract.

We report the clinicopathologic and immunohistochemical features of 18 cases of confirmed primary synovial sarcoma of the gastrointestinal tract. The neoplasms arose in 10 women and 8 men ranging in age from 23 to 81 years (mean: 50; median: 57.5 years). The tumors for which size was known ranged from 1.8 to 15.0 cm (mean: 5.2; median: 5.1 cm). Microscopically, 14 synovial sarcomas were of the monophasic type, 2 were biphasic, and 2 were poorly differentiated. Immunohistochemical analysis of 4 cases showed strong, diffuse staining for SS18::SSX (4/4 cases). Pancytokeratin and EMA immunohistochemistry were performed on 13 and 9 tumors, respectively, and each showed patchy-to-diffuse staining. By reverse-transcription PCR, 3 cases were positive for the SS18::SSX1, and 2 cases were positive for the SS18::SSX2 gene fusion. Six cases contained an SS18 gene rearrangement by fluorescence in situ hybridization, and next-generation sequencing identified an SS18::SSX2 gene fusion in one case. Clinical follow-up information was available for 9 patients (4 months to 4.6 years; mean, 2.8 y; median: 29 months), and one patient had a recent diagnosis. Three patients died of disease within 41 to 72 months (mean, 56 months) of their diagnosis. Five patients were alive without evidence of disease 4 to 52 months (mean, 17.6 months) after surgery; of whom 1 of the patients received additional chemotherapy treatment after surgery because of recurrence of the disease. A single patient was alive with intraabdominal recurrence 13 months after surgery. We conclude that synovial sarcoma of the gastrointestinal tract is an aggressive tumor, similar to its soft tissue counterpart, with adverse patient outcomes. It is important to distinguish it from morphologically similar gastrointestinal tract lesions that may have different treatment regimens and prognoses.

Systemic diseases affecting the GI tract: A review of clinical and histopathologic manifestations.

A variety of systemic diseases may affect the gastrointestinal (GI) tract. Since the GI tract responds to injury in limited ways, identifying these processes may be challenging, especially on small endoscopic biopsies. This article reviews the clinicopathologic features of commonly encountered systemic diseases affecting the tubular GI tract: sarcoidosis, graft vs. host disease, mast cell disorders, systemic sclerosis, and IgG-4 related disease. In addition, we offer guidance in differentiating them from their mimics.

Lipoblastoma-Like Tumor and Fibrosarcoma-Like Lipomatous Neoplasm Represent the Same Entity: A Clinicopathologic and Molecular Genetic Study of 23 Cases Occurring in Both Men and Women at Diverse Locations.

Lipoblastoma-like tumor (LLT) is a benign soft tissue tumor demonstrating mixed morphologic features of lipoblastoma, myxoid liposarcoma, and spindle cell lipoma but lacking genetic alterations associated with those tumors. LLT was originally thought to be specific to the vulva but has since been reported in the paratesticular region. The morphologic features of LLT overlap with those of "fibrosarcoma-like lipomatous neoplasm" (FLLN), a rare, indolent adipocytic neoplasm considered by some to form part of the spectrum of atypical spindle cell and pleomorphic lipomatous tumor. We compared the morphologic, immunohistochemical, and genetic features of 23 tumors previously classified as LLT (n = 17) and FLLN (n = 6). The 23 tumors occurred in 13 women and 10 men (mean age, 42 years; range, 17 to 80 years). Eighteen (78%) cases arose in the inguinogenital region, whereas 5 tumors (22%) involved noninguinogenital soft tissue, including the flank (n = 1), shoulder (n = 1), foot (n = 1), forearm (n = 1), and chest wall (n = 1). Microscopically, the tumors were lobulated and septated, with variably collagenized fibromyxoid stroma, prominent thin-walled vessels, scattered univacuolated or bivacuolated lipoblasts, and a minor component of mature adipose tissue. Using immunohistochemistry, 5 tumors (42%) showed complete RB1 loss, with partial loss in 7 cases (58%). RNA sequencing, chromosomal microarray, and DNA next-generation sequencing study results were negative for significant alterations. There were no clinical, morphologic, immunohistochemical, or molecular genetic differences between cases previously classified as LLT or FLLN. Clinical follow-up (11 patients [48%]; range, 2-276 months; mean, 48.2 months) showed all patients were alive without disease, and only one patient had experienced a single local recurrence. We conclude that LLT and FLLN represent the same entity, for which "LLT" seems most appropriate. LLT may occur in either sex and any superficial soft tissue location. Careful morphologic study and appropriate ancillary testing should allow for the distinction of LLT from its potential mimics.

Current concepts in the diagnosis and pathobiology of intraepithelial neoplasia: A review by organ system.

Answer questions and earn CME/CNE In this report, a team of surgical pathologists has provided a review of intraepithelial neoplasia in a host of (but not all) anatomic sites of interest to colleagues in various medical specialties, namely, uterine cervix, ovary, breast, lung, head and neck, skin, prostate, bladder, pancreas, and esophagus. There is more experience with more readily accessible sites (such as the uterine cervix and skin) than with other anatomic sites, and the lack of uniform terminology, together with divergent biology in various sites, makes it difficult to paint a unifying, relevant portrait. The authors' aim was to provide a framework from which to move forward as we care for patients with such precancerous lesions. CA Cancer J Clin 2016;66:408-436. © 2016 American Cancer Society.

Perianal Paget's disease as spread from non-invasive colorectal adenomas.

AIMS: Paget's disease of the perianal skin is a rare form of extramammary Paget's disease, and may be a primary intraepithelial adnexal neoplasm or secondary due to spread from an underlying colorectal lesion, nearly always colorectal adenocarcinoma. Secondary perianal Paget's disease associated with non-invasive colorectal adenomas is exceedingly uncommon, with only a few reported cases. METHODS AND RESULTS: Herein, we present the clinical and pathological features of the largest series of secondary perianal Paget's disease arising in association with colorectal adenomas. There was gender parity and the median age was 72 years (range = 68-76 years). In all cases, perianal Paget's disease was associated with colorectal adenomas, including three (75%) conventional tubular adenomas and one (25%) tubulovillous adenoma with serrated foci. All adenomas had high-grade dysplasia and one had intramucosal adenocarcinoma (lamina propria invasion; Tis), but all lacked submucosal invasion. The intraepithelial Paget's cells showed a colorectal phenotype by immunohistochemistry in all cases. At follow-up, two patients had no evidence of disease at 6 and 87 months, one had residual perianal Paget's disease at 8 months and one developed invasive adenocarcinoma of the perianal tissue at 36 months. CONCLUSIONS: Similar to its mammary analogue, secondary perianal Paget's disease may arise in association with invasive and/or in-situ colorectal lesions. Although the latter is an uncommon presentation of a recognised rare disease, knowledge of this phenomenon is important to forestall overdiagnosis of invasion and potential overtreatment. The clinical course is variable, such that close follow-up is required.

Cell polarity (the 'four lines') distinguishes gastric dysplasia from epithelial changes in reactive gastropathy.

AIMS: Gastric dysplasia is a risk factor for synchronous and subsequent gastric carcinoma. Distinguishing gastric dysplasia from reactive changes is subject to interobserver disagreement and is a frequent reason for expert consultation. We previously used assessment of surface cell polarity (the 'four lines') as a key feature to decrease equivocal diagnoses in Barrett oesophagus. In the current study, we examined for the presence or absence of the four lines in gastric dysplasia and reactive gastropathy. MATERIALS AND METHODS: The study includes all (n = 91) in-house biopsies with at least gastric dysplasia from the surgical pathology archives of two academic institutions during a 5-year period from 2008 to 2012. A reactive gastropathy group (n = 60) was created for comparison. RESULTS: The dysplasia/neoplasia group was comprised of 14 biopsies of gastric foveolar-type dysplasia, 59 of intestinal-type dysplasia, 14 with dysplasia in fundic gland polyps, three pyloric gland adenomas and one oxyntic gland adenoma. Loss of surface cell polarity was seen in all 88 dysplasia cases with evaluable surface epithelium. All 57 reactive gastropathy cases with evaluable surface epithelium showed intact surface cell polarity except in focal areas directly adjacent to erosions in 17 cases, where the thin wisp of residual surface mucin could not be appreciated on haematoxylin and eosin. CONCLUSION: Surface cell polarity (the four lines) was lost in all gastric dysplasia biopsies with evaluable surface epithelium and maintained in all biopsies of reactive gastropathy. Caution should be taken in using this feature adjacent to erosions in reactive gastropathy.

Lymphogranuloma venereum (LGV) of the anorectum: evaluation of clinicopathological associations and the utility of a novel RNA in-situ hybridisation stain.

AIMS: Recent studies from multiple global regions have reported a resurgence of lymphogranuloma venereum (LGV) proctitis, which is caused by Chlamydia trachomatis (CT). LGV proctitis is histologically indistinguishable from other forms of sexually transmitted proctitis and is difficult to differentiate from inflammatory bowel disease. While immunohistochemical stains are available for syphilis, there is no commonly available stain for the tissue identification of CT. MATERIALS AND METHODS: From 200 positive CT nucleic acid tests (NAT) from anorectal swabs, we identified 12 patients with biopsies collected from the distal colorectum or anus within 90 days of the positive NAT. We collected basic demographic information and tabulated clinical and histological findings. We examined the performance of a novel RNA in-situ hybridisation (ISH) stain targeting CT 23s rRNA on these 12 cases and 10 controls from the anorectum. RESULTS: All 12 patients were male; nine were HIV+, two had concurrent gonococcal infection, one had concurrent syphilis and one had cytomegalovirus co-infection. The majority of biopsies (11 of 12) showed mild or moderate acute inflammation, had a prominent lymphoplasmacytic infiltrate (eight of 11) and lacked marked crypt distortion (10 of 10). The RNA ISH stain was positive in 10 of 12 cases (sensitivity 83%). One case showed equivocal staining. No controls showed definitive positive staining (specificity 100%). One had equivocal staining. CONCLUSION: Our series showed that anorectal LGV had similar histological findings to those of prior STI proctitis series predominantly comprised of syphilis. The novel RNA ISH stain was sensitive and specific and may show utility in differentiating types of STI proctitis.

Multifocal Cryoballoon Ablation for Eradication of Barrett's Esophagus-Related Neoplasia: A Prospective Multicenter Clinical Trial.

INTRODUCTION: Ablation of Barrett's esophagus (BE) is the preferred approach for the treatment of neoplasia without visible lesions. Limited data on cryoballoon ablation (CBA) suggest its potential clinical utility. We evaluated the safety and efficacy of CBA in a multicenter study of patients with neoplastic BE. METHODS: In a prospective clinical trial, 11 academic and community centers recruited consecutive patients with BE of 1-6 cm length and low-grade dysplasia, high-grade dysplasia (HGD), or intramucosal adenocarcinoma (ImCA) confirmed by central pathology. Patients with symptomatic pre-existing strictures or visible BE lesions had dilation or endoscopic mucosal resection (EMR), respectively, before enrollment. A nitrous oxide cryoballoon focal ablation system was used to treat all visible columnar mucosa in up to 5 sessions. Study end points included complete eradication of all dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1 year. RESULTS: One hundred twenty patients with BE with ImCA (20%), HGD (56%), or low-grade dysplasia (23%) were enrolled. In the intention-to-treat analysis, the CE-D and CE-IM rates were 76% and 72%, respectively. In the per-protocol analysis (94 patients), the CE-D and CE-IM rates were 97% and 91%, respectively. Postablation pain was mild and short lived. Fifteen subjects (12.5%) developed strictures requiring dilation. One patient (0.8%) with HGD progressed to ImCA, which was successfully treated with EMR. Another patient (0.8%) developed gastrointestinal bleeding associated with clopidogrel use. One patient (0.8%) had buried BE with HGD in 1 biopsy, not confirmed by subsequent EMR. DISCUSSION: In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted (clinicaltrials.gov registration NCT02514525).

A novel group of HPV-related adenocarcinomas of the lower anogenital tract (vagina, vulva, and anorectum) in women and men resembling HPV-related endocervical adenocarcinomas.

Human papillomavirus (HPV) is an oncogenic virus associated with the development of several human cancers. Primary vaginal, vulvar, and anal adenocarcinomas are rare and, to date, have rarely been shown to be associated with HPV infection. We report a series of nine HPV-related adenocarcinomas of the lower anogenital tract distal to the cervix. The tumors involved the vagina (4), anorectum (3), and vulva (2). Two of the three anorectal cases involved men. Patients presented with a vulvar or vaginal mass/nodule, painless rectal bleeding, or during screening colonoscopy. Lesions ranged in size from 3.2 to 8.4 cm. The most salient morphologic characteristic was the presence of papillary or villiform/villoglandular architecture in all cases. Tumors displayed features similar to those of usual type high-risk HPV-related endocervical adenocarcinoma, namely, mucinous or mucin-poor (pseudoendometrioid) features or a hybrid of these, with columnar cells with crowded, cigar-shaped to ovoid irregular nuclei. Mitoses (mostly apical) and apoptotic bodies were easily identified. Adenosis was present in two vaginal cases. One anal tumor featured abundant intracytoplasmic mucin that was multivacuolated in some areas imparting a "clear cell"-like appearance. All tumors were diffusely and strongly positive for p16. Seven of seven tested cases were positive for high-risk HPV by in situ hybridization or polymerase chain reaction. Follow-up information, available in five patients, revealed two local recurrences but no tumor related deaths or distant metastases. We report the first well-documented series of HPV-associated primary adenocarcinomas of the vagina, vulva, and anorectum and broaden the spectrum of HPV-related neoplasia involving the lower anogenital tract in both women and men.

EWSR1/FUS-CREB fusions define a distinctive malignant epithelioid neoplasm with predilection for mesothelial-lined cavities.

Gene fusions constitute pivotal driver mutations often encoding aberrant chimeric transcription factors. However, an increasing number of gene fusion events have been shown not to be histotype specific and shared among different tumor types, otherwise completely unrelated clinically or phenotypically. One such remarkable example of chromosomal translocation promiscuity is represented by fusions between EWSR1 or FUS with genes encoding for CREB-transcription factors family (ATF1, CREB1, and CREM), driving the pathogenesis of various tumor types spanning mesenchymal, neuroectodermal, and epithelial lineages. In this study, we investigate a group of 13 previously unclassified malignant epithelioid neoplasms, frequently showing an epithelial immunophenotype and marked predilection for the peritoneal cavity, defined by EWSR1/FUS-CREB fusions. There were seven females and six males, with a mean age of 36 (range 9-63). All except three cases occurred intra-abdominally, including one each involving the pleural cavity, upper, and lower limb soft tissue. All tumors showed a predominantly epithelioid morphology associated with cystic or microcystic changes and variable lymphoid cuffing either intermixed or at the periphery. All except one case expressed EMA and/or CK, five were positive for WT1, while being negative for melanocytic and other mesothelioma markers. Nine cases were confirmed by various RNA-sequencing platforms, while in the remaining four cases the gene rearrangements were detected by FISH. Eleven cases showed the presence of CREM-related fusions (EWSR1-CREM, 7; FUS-CREM, 4), while the remaining two harbored EWSR1-ATF1 fusion. Clinically, seven patients presented with and/or developed metastases, confirming a malignant biologic potential. Our findings expand the spectrum of tumors associated with CREB-related fusions, defining a novel malignant epithelioid neoplasm with an immunophenotype suggesting epithelial differentiation. This entity appears to display hybrid features between angiomatoid fibrous histiocytoma (cystic growth and lymphoid cuffing) and mesothelioma (peritoneal/pleural involvement, epithelioid phenotype, and cytokeratin and WT1 co-expression).

The inverted appendix - a potentially problematic diagnosis: clinicopathologic analysis of 21 cases.

AIMS: Inverted appendices are rare, but have the potential to cause diagnostic confusion among endoscopists and pathologists. The aim of this study was to describe the clinicopathological features of inverted appendices seen at our institution over the last 30 years. METHODS AND RESULTS: Twenty-one inverted appendices were identified and the clinical and pathological features reviewed. Patients were predominantly middle-aged women. Most cases were detected incidentally on colonoscopy. Endoscopically, inverted appendices appeared polypoid in the proximal caecum. All resections featured associated pathological processes, including endometriosis (n = 3), inflammatory mucocoele (n = 1), low-grade appendiceal mucinous neoplasm (n = 2), traditional serrated adenoma (n = 1) and inflammatory fibroid polyp (n = 1). Five cases were endoscopically mischaracterised as caecal polyps and removed via polypectomy; initial pathological impressions were erroneous in most cases. All polypectomies featured a dome-like configuration covered by mucosa on the convex surface; the majority had aggregates of ganglion cells and neural plexi embedded in muscularis propria. The vast majority of cases, regardless of the procedure, showed lymphoid aggregates. Among post-polypectomy patients with follow-up, none experienced perforation-associated morbidity despite the histological presence of muscularis propria. CONCLUSIONS: The diagnosis of an inverted appendix should be considered in polypectomy specimens from the caecum or appendiceal orifice with (i) dome-like tissue configuration covered by mucosa on the convex surface, (ii) a deep, robust smooth muscle component with ganglion cells (muscularis propria) and (iii) associated lymphoid aggregates. Prompt recognition on H&E will avoid unnecessary time and resource investment.

Cerebral pleomorphic liposarcoma: Clinicopathologic findings.

Pleomorphic liposarcoma is the rarest subtype of liposarcoma. Involvement of the central nervous system by pleomorphic liposarcoma is exceptional. We present a 62-year-old woman with an intraparenchymal mass involving the left frontoparietal lobes. Histologic examination demonstrated a mesenchymal neoplasm with a dense reticulin network and pleomorphic lipoblasts. Immunohistochemical stain for adipophilin highlighted intracytoplasmic vacuoles. MDM2 immunostain was negative. A diagnosis of pleomorphic liposarcoma was made. There was no evidence of an extracranial primary neoplasm by imaging or physical exam. Pleomorphic liposarcoma may rarely present as a solitary intracranial mass, an entity that must be entertained in the differential diagnosis of pleomorphic tumors involving the brain.
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The outlet patch: gastric heterotopia of the colorectum and anus.

AIMS: Gastric heterotopia (GH) has been described throughout the gastrointestinal tract. However, the colorectal region is an extremely rare location for it. We describe the clinicopathological features of GH of the colon, rectum and anus. METHODS AND RESULTS: We identified 33 cases in 20 males and 13 females (median age = 54 years; range = 4 months-73 years). Sites included the rectum (n = 26), anus (n = 4), ileocaecal junction (n = 1), ascending colon (n = 1) and descending colon (n = 1). Presenting symptoms (n = 27) included haematochezia (41%) and altered bowel habits (4%); 15 patients (55%) were asymptomatic. On colonoscopy (n = 31), all appeared as solitary lesions (median size = 6.5 mm, range = 2-55 mm), either as polyps (61%), raised erythematous patches (23%), an ulcer (10%), within a rectal diverticulum (3%) or a haemorrhoid (3%). Patients were managed by polypectomy. One with an associated carcinoma in the area of GH underwent resection. No morbidity related to GH itself was reported following excision. Histologically, heterotopic gastric mucosa was oxyntic (85%), mixed oxyntic and non-oxyntic (12%) and not specified (3%) types. In five patients a pyloric gland adenoma (PGA) arose from heterotopic gastric mucosa, two of which contained a focus of invasive adenocarcinoma. One case had associated surface foveolar-type low-grade dysplasia. Another had associated adenocarcinoma arising from the heterotopic mucosa. One example harboured Helicobacter pylori organisms. CONCLUSIONS: We highlight the features of GH in the distal GIT - the 'outlet patch'. Association with PGA, surface dysplasia and adenocarcinoma suggests that lower tract GH can undergo neoplastic transformation.

Multifocal nitrous oxide cryoballoon ablation with or without EMR for treatment of neoplastic Barrett's esophagus (with video).

BACKGROUND AND AIMS: Endoscopic cryotherapy can eradicate neoplastic Barrett's esophagus (BE). A new contact cryoballoon focal ablation system (CbFAS)) freezes esophageal mucosa with nitrous oxide. We studied the safety and efficacy of CbFAS for complete eradication of neoplastic Barrett's esophagus. METHODS: In a prospective clinical trial, consecutive BE patients with confirmed neoplasia (low-grade dysplasia [LGD], high-grade dysplasia [HGD], and/or intramucosal adenocarcinoma [ImCA]), at least 1 cm of BE, with or without prior ablation, were treated with a dose 10 seconds of spray per site. EMR was performed for nodular lesions. Treatments were repeated every 10 to 12 weeks until complete eradication, with a maximum of 5 treatments. Primary outcomes were complete eradication of all dysplasia (CE-D) and complete eradication of intestinal metaplasia (CE-IM) at 1 year (intention-to-treat analysis). RESULTS: Forty-one assessable patients (22 treatment naive, 19 previously ablated) with LGD (n = 13), HGD (n = 23), or ImCA (n = 5) were treated. The median procedure time was 30 minutes. The median number of ablation procedures for CE-IM was 3 (interquartile range, 2-4). Overall 1-year CE-D and CE-IM rates were 95% and 88%, respectively. CE-D rate was significantly lower (67%) in those with ultra-long BE compared with those with <8 cm (100%, P = .02). Median pain scores were zero at day 1. Four patients (9.7%) developed mild dysphagia from stenoses requiring dilation. One patient on aspirin developed upper GI bleeding that did not require therapy. CONCLUSIONS: Multifocal nitrous oxide cryotherapy using CbFAS is a promising, highly effective, and safe endoscopic treatment for primary or rescue therapy of BE-associated neoplasia and IM. (Clinical trial registration number: NCT02534233.).

Targeted next-generation sequencing supports epidermoid metaplasia of the esophagus as a precursor to esophageal squamous neoplasia.

Esophageal epidermoid metaplasia is a rare condition that involves the proximal-to-middle third of the esophagus. It is sharply demarcated and defined histologically by epithelial hyperplasia, a prominent granular cell layer, and superficial hyperorthokeratosis. In addition, preliminary studies have suggested an association between esophageal epidermoid metaplasia and esophageal squamous neoplasia (squamous dysplasia and esophageal squamous cell carcinoma). To further characterize esophageal epidermoid metaplasia and better define its relationship to squamous neoplasia of the esophagus, we performed targeted next-generation sequencing on uninvolved esophageal squamous mucosa and matching esophageal epidermoid metaplasia specimens from 18 patients. Further, we evaluated both synchronous and metachronous high-grade squamous dysplasia/esophageal squamous cell carcinoma by next-generation sequencing from 5 of the 18 (28%) patients, and compared these findings to corresponding esophageal epidermoid metaplasia specimens. Targeted next-generation sequencing revealed 12 of 18 (67%) esophageal epidermoid metaplasia specimens' harbored alterations in genes often associated with esophageal squamous cell carcinoma. The most frequently mutated genes consisted of TP53 (n=10), PIK3CA (n=2), EGFR (n=2), MYCN (n=1), HRAS (n=1), and the TERT promoter (n=1). Sequencing of synchronous and metachronous high-grade squamous dysplasia/esophageal squamous cell carcinoma identified shared genetic alterations with corresponding esophageal epidermoid metaplasia specimens that suggests a clonal relationship between these entities. In addition, the presence of a TP53 mutation in esophageal epidermoid metaplasia specimens correlated with concurrent or progression to high-grade squamous dysplasia/esophageal squamous cell carcinoma. No genetic alterations were detected in uninvolved esophageal squamous mucosa. On the basis of these findings, we conclude esophageal epidermoid metaplasia is a precursor to in situ and invasive esophageal squamous neoplasia. Further, the detection of TP53 mutations in esophageal epidermoid metaplasia specimens may serve as an early detection biomarker for high-grade squamous dysplasia/esophageal squamous cell carcinoma.

Gastrointestinal tract spindle cell lesions--just like real estate, it's all about location.

Interpretation of gastrointestinal tract mesenchymal lesions is simplified merely by knowing in which anatomic layer they are usually found. For example, Kaposi sarcoma is detected on mucosal biopsies, whereas inflammatory fibroid polyp is nearly always in the submucosa. Gastrointestinal stromal tumors (GISTs) are generally centered in the muscularis propria. Schwannomas are essentially always in the muscularis propria. Mesenteric lesions are usually found in the small bowel mesentery. Knowledge of the favored layer is even most important in interpreting colon biopsies, as many mesenschymal polyps are encountered in the colon. Although GISTs are among the most common mesenchymal lesions, we will concentrate our discussion on other mesenchymal lesions, some of which are in the differential diagnosis of GIST, and point out some diagnostic pitfalls, particularly in immunolabeling.

Polypoid stromal lesions of the intestines.

Interpretation of intestinal mesenchymal lesions is simplified merely by knowing in which anatomic layer they are usually found. For example, Kaposi sarcoma is detected on mucosal biopsies, whereas inflammatory fibroid polyp is almost always in the submucosa. Gastrointestinal stromal tumours (GIST) are centred generally in the muscularis propria. Schwannomas are essentially always in the muscularis propria. Knowledge of the favoured layer is also most important in interpreting colon biopsies, as many mesenchymal polyps are encountered in the colon. Herein we discuss several mesenchymal lesions and point out some diagnostic pitfalls.

Esophageal leukoplakia or epidermoid metaplasia: a clinicopathological study of 18 patients.

Oral leukoplakia is a relatively common, painless disorder of the oral mucosa. It predominantly affects middle-aged to elderly men and has a strong association with tobacco smoking and alcohol intake. Concomitant histological findings of hyperorthokeratosis and a well-developed granular cell layer, termed orthokeratotic dysplasia, are often associated with oral squamous cell carcinoma. In contrast, analogous lesions within the esophagus, termed esophageal epidermoid metaplasia, are rarely encountered and poorly described in the literature. To better characterize the clinicopathological features of this entity, we have collected 25 cases from 18 patients. Patients ranged in age from 37 to 81 years (mean, 61.5 years), with a slight female predominance (10/18, 56%). On presentation, a majority of patients complained of dysphagia (10/18, 56%). Past medical history was significant for tobacco smoking or long history of second-hand smoke in 11 (61%) patients and alcohol intake in 7 (39%) patients. Seventeen (94%) patients with esophageal epidermoid metaplasia were located within the middle-to-distal esophagus. Histologically, all cases were sharply demarcated and characterized by epithelial hyperplasia, a thickened basal layer, acanthotic midzone, a prominent granular cell layer, and superficial hyperorthokeratosis. Adjacent high-grade squamous dysplasia and/or squamous cell carcinoma were seen in 3 out of 18 (17%) patients. Follow-up information was available for 13 out of 18 (72%) patients and ranged from 2 to 8.3 years (mean, 2.3 years). Seven of the 13 (54%) patients had persistent disease; however, none of them developed squamous dysplasia or squamous cell carcinoma. In an effort to assess the incidence of esophageal epidermoid metaplasia, 198 consecutive esophageal biopsies were prospectively surveyed over a 6-month period at three academic institutions. No cases were identified within this time frame. In summary, esophageal epidermoid metaplasia is a rare condition affecting the middle-to-distal esophagus in middle-aged to elderly females. The occurrence of adjacent high-grade squamous dysplasia and/or squamous cell carcinoma warrants close follow-up.