A CASE OF LEIOMYOMA OF THE LAMINA MUSCULARIS MUCOSAE OF THE ESOPHAGUS WITH A COMPLICATION OF CARCINOMA IN SITU OF THE OVERLYING MUCOSA

An extremely rare case of leiomyoma originating in the lamina muscularis mucosae of the esophagus with a complication of carcinoma in situ in its overlying mucosa was reported. The patient was a 53-year-old male who complained of a feeling of abdominal fullness. A small, elevated tumor was found in the middle portion of the esophagus by esophagoscopy. Biopsy specimens showed it to be squamous cell carcinoma. The resected material revealed the tumor mass to be composed of both a leiomyoma, measuring 0.8 × 0.6 × 0.25 cm, which continued from the lamina muscularis mucosae, and carcinoma in situ and dysplasia in the overlying mucosa of the leiomyoma. The mucosa apart from that covering the leiomyoma was intact. It was speculated that chronic stimulation of the epithelium covering the leiomyoma might have induced the dysplasia and carcinoma in situ . ACTA PATHOL. JPN. 37: 1845–1851, 1987.     

Double muscularis mucosae in Barrett's esophagus.

To clarify the histology and morphogenesis of the double muscularis mucosae in Barrett's esophagus, eight specimens resected from patients with Barrett's esophagus were compared histopathologically with 352 specimens resected from patients without Barrett's esophagus. A double muscularis mucosae was observed in seven (87.5%) of the eight cases with Barrett's esophagus, but in none of the 352 cases without Barrett's esophagus. The mucosa in the segment of Barrett's esophagus consisted of columnar epithelium, a superficial lamina propria, a superficial muscularis mucosae, a deep lamina propria, and a deep muscularis mucosae. The distal end of the superficial muscularis mucosae was connected to the deep muscularis mucosae at the esophagogastric junction, and its proximal end was located in fibrous tissue below the squamocolumnar junction of the mucosal epithelium or the distal edge of the erosive lesion. The deep muscularis mucosae in the portion with Barrett's esophagus was continuous with the original muscularis mucosae of the proximal esophagus and muscularis mucosae of the stomach. Barrett's esophagus is considered to be not merely a metaplastic lesion within the epithelium, but a newly developed lesion containing columnar epithelium, lamina propria, and a superficial muscularis mucosae on the lamina propria of the esophageal mucosa.     

The organization of the lamina muscularis mucosae in the human esophagus

The structural organization of the lamina muscularis mucosae of the human esophagus was studied by light microscopy and scanning electron microscopy (SEM). The organization of the lamina muscularis mucosae varied considerably among the cervical, the thoracic, and the abdominal part of the esophagus. In the cervical part, the lamina muscularis mucosae was not well developed and only islets of the smooth muscle bundles were scattered within the connective tissue. In the thoracic part, the lamina muscularis mucosae consisted of several layers of smooth muscle bundles, individual muscle cells of which ran in a longitudinal direction. In the abdominal esophagus near the cardia, the muscular bundles in the lamina muscularis mucosae ran in various directions forming a reticular configuration. The differences in density and arrangement of the lamina muscularis mucosae are discussed in relation to the swallowing of food and submucosal invasion of esophageal cancer.     

Architectural morphometry in ulcerative colitis with dysplasia

Semi-automatic image analysis was used to assess the architectural features of normal colorectal mucosa and ulcerative colitis with and without dysplasia. Eight measured and derived morphometric variables were compared with the histological grading. The main data-set variation was due to: (1) the area of mucosa and epithelium per unit length of muscularis mucosae; (2) mean mucosal and epithelial height; and (3) the percentage epithelium and number of crypts per unit length of muscularis mucosae. Discriminant analysis using the variables mean epithelial height and mean lamina propria area per unit length of muscularis mucosae separated normals (n = 10) from high-grade dysplasia (8). The classification rule allocated low-grade dysplasia (8) to the high-grade category and 60% of regeneration cases (10) to the normal mucosa group. Scatter plots of the two discriminating variables separated normal and regenerative mucosa from dysplasia. Histological review of overlapping cases allowed redesignation of a high-grade dysplasia lesion as low grade. Architectural morphometry may be of use in assessing premalignant mucosal changes in ulcerative colitis as a guide to patient surveillance and therapy.     

Further studies on the musculo-fibrous anomaly of the Barrett's mucosa in esophageal carcinomas.

A total of 50 esophagi with carcinoma were reviewed for the presence of histological changes in the subepithelial tissues of the Barrett's mucosa. Those changes consisted in the thickening of the muscularis mucosae, the presence of muscle fibres in the lamina propria mucosae, fibrosis of the submucosa and sometimes total obliteration of the subepithelial tissues by collagen-rich sclerosis. Those changes have been connoted as "musculo-fibrous anomaly". Barrett's mucosa was present in all 18 specimens with adenocarcinoma and in 13 of the remaining 32 specimens with squamous cell carcinoma. Musculo-fibrous anomaly of the Barrett's mucosa occurred in all 18 specimens with adenocarcinoma and in 10 of the 13 specimens with a concomitantly growing squamous cell carcinoma. Esophageal and metaplastic glands were surrounded, compressed and deformed by the fibrotic tissue. The histological changes described explain the difficulties in the differential diagnosis--in biopsy specimens--between normal glands or glands with dysplastic changes "trapped" in the collagen-rich fibrotic tissue and true invasive adenocarcinoma of the Barrett's esophagus.     

The pattern of invasion of early carcinomas in Barrett's esophagus is dependent on the depth of infiltration

The differential diagnosis “high-grade intraepithelial neoplasia” or “well-differentiated Barrett's adenocarcinoma limited to the mucosa” is controversial. We investigated 277 endoscopically resected specimens of early Barrett's carcinoma. Depth of infiltration was classified as follows: m 1=carcinoma limited to Barrett's mucosa; m 2=carcinoma infiltrating the neo-muscularis mucosae; m 3=infiltration of the original lamina propria of the esophageal mucosa; m 4=infiltration of the original muscularis mucosae; sm 1, sm 2, and sm 3=infiltration into the upper third, middle third, and lower third of the submucosa. The pattern of invasion was classified and graded as follows: tubular (D 0)=only neoplastic tubuli showing cytologic criteria of malignancy – no tumor cell dissociation; dissociation grade 1 (D 1)=few dissociated tumor cells; D 2=moderate amount of dissociated tumor cells; D 3=pronounced tumor cell dissociation. 74–96% of m 1–m 4 Barrett's carcinomas limited to the mucosa have a D 0-pattern. Tubular invasion decreases only when the submucosa has been infiltrated (sm 1: 70.4%, sm 2: 30.0%, sm 3: 24.0%). Our study shows that the pattern of invasion in early cancer in Barrett's esophagus statistically significantly depends on depth of infiltration.     

Mesenchymal tumors of muscularis mucosae of colon and rectum are benign leiomyomas that should be separated from gastrointestinal stromal tumors--a clinicopathologic and immunohistochemical study of eighty-eight cases.

Most mesenchymal tumors of the gastrointestinal tract are currently classified as specific gastrointestinal stromal tumors. However, true leiomyomas are more common in the esophagus, and they have been occasionally noted in the colon and rectum, but the small number of reported cases does not allow for clinicopathologic profiling. This study was undertaken to characterize 88 tumors of the muscularis mucosae of the colon and rectum. Seventy tumors were obtained form the files of AFIP and 18 cases from the Department of Pathology of the Haartman Institute of the University of Helsinki. The lesions, except one, were removed by snare polypectomy as incidental lesions at cancer or polyp surveillance; one small tumor was an incidental finding in the rectal resection specimen. The tumors had a significant male predominance in both institutions (overall 2.4:1). They occurred in age range of 38 to 85 years (median 62 years). The lesions were typically small (range 1 to 22 mM, median 4 mM) and located predominantly in the rectum and sigmoid (72%). All tumors were composed of well-differentiated, eosinophilic smooth muscle cells that were seen immediately beneath the mucosa obliterating the muscularis mucosae layer and merging with it. Two tumors had significant atypia ("symplastic leiomyoma"); mitotic activity was seen in one of these tumors, but not in others. The lesional cells were uniformly positive for smooth muscle actin and desmin and negative for CD34, CD117 and S100-protein, based on immunohistochemical studies on 20 to 24 cases with each marker. No gastrointestinal stromal tumors were identified among the tumors of muscularis mucosae, and no CD117-positive cells, except mast cells, were seen in the muscularis mucosae layer. None of the patients had morbidity related to the tumor. Based on follow-up data on 29 patients, leiomyomas of muscularis mucosae are benign. They should be separated from gastrointestinal stromal tumors that have a clinicopathologic spectrum including frequent disease-related mortality. Snare polypectomy is an adequate treatment, but ensuring the complete removal and follow-up are necessary precautions for tumors with any atypia or mitotic activity.     

Collecting and paramuscular venules in glandular mucosa of rat stomach.

Blood from the rat gastric mucosa is drained by collecting venules running from the subepithelial layer towards the lamina muscularis mucosae. Details of their structure were studied in translucent, flat strips of the glandular stomach, in thick sections of glandular mucosa cleared in mineral oil and in semi-thin plastic sections. The number and dimensions of collecting venule outlets revealed in flat strips of gastric mucosa increased after administration of atropine and papaverine and intravital ligation of the portal vein in comparison with that of intact animals or animals with intravitally ligated portal vein but without administration of relaxing agents. In hyperemic mucosa short venules running parallel to the lamina muscularis mucosae (paramuscular venules) and draining collecting venules were distinctly visible. Saccular outlets equipped with triangular protrusions usually intervened between these vessels, probably directing blood flow. Collecting venules were straight, curved, extended or two-armed. Furthermore, numerous collecting venules contained circumscribed dilatations (sacculi) connected with the lumen of the collecting venule. Connection of paramuscular and submucosal veins occurred within the muscularis mucosae. Thus, contraction of the muscularis mucosae might control the outflow of venous blood from the gastric mucosa. Conceivably, alternate contraction and relaxation of muscularis mucosae could cause expansion and collapse of collecting venules which, in turn, would facilitate the movement of glandular content to the surface of the stomach and/or movement of interstitial fluid between cells.     

Overexpression of decoy receptor 3 in precancerous lesions and adenocarcinoma of the esophagus

Overexpression of decoy receptor (DcR) 3 protein, a recently discovered member of the tumor necrosis factor receptor superfamily, was examined in 40 esophagogastrectomy specimens containing areas of Barrett esophagus (n = 27), low-grade dysplasia (n = 27), high-grade dysplasia or carcinoma in situ (n = 22), and esophageal adenocarcinoma (EAC; n = 28) with immunohistochemical analysis. The results revealed significantly more overexpression of DcR3 in high-grade dysplasia or carcinoma in situ and EAC than in benign esophageal mucosa (both P < .0001), Barrett esophagus (both P < .001), and low-grade dysplasia (P < .01 and P = .033, respectively). Low-grade dysplasia also showed significant overexpression of DcR3 compared with benign esophagus (P < .05) but not with Barrett esophagus (P > .05). DcR3 overexpression seems to negatively correlate with the grade of EAC. Our results suggest that overexpression of DcR3 protein might aid in the diagnosis of high-grade dysplasia or carcinoma in situ and EAC and also might serve as a potential therapeutic target.     

Smooth Muscle Cell Abnormalities Associated with Gastric ECL Cell Carcinoids

The histologic and immunohistochemical study of 45 ECL cell gastric carcinoids and of the extratumoral gastric mucosa revealed four variants of smooth muscle cell abnormalities: (1) hypertrophy of muscularis mucosae trapped within the tumors, a finding occurring in 76.5% of cases; (2) proliferation of stromal smooth muscle cells originating from the muscularis mucosae and mostly associated with tumor invasion of the submucosa (seen in 93.9% of cases with abundant stromal component of the tumors); (3) occurrence of frequent, prominent aggregates of smooth muscle cells in the lamina propria of the antral (but not of the fundic) mucosa of the stomach (found in 41.7% of cases); and (4) increased thickness of the extratumoral muscularis mucosae in the fundic (but not in the antral) mucosa of patients with gastric carcinoids. In addition, localized muscle cell proliferation was also associated with foci of micronodular hyperplasia of endocrine cells in the extratumoral mucosa. These findings were neither observed in control cases of gastric adenocarcinoma, gastric peptic ulcer, and duodenal peptic ulcer (10 unselected cases from each group) nor were they observed in 10 subjects with normal gastric mucosa collected at autopsy. With the possible exception of the increased thickness of the extratumoral fundic muscularis mucosae, which may be influenced by the mucosal inflammatory process, it is suggested that the present findings represent a proliferative response of smooth muscle cells to basic fibroblastic growth factor whose production by gastric carcinoids and their precursor lesions has recently been demonstrated.     

Esophageal adenocarcinoma that probably originated in the esophageal gland duct: A case report

A case of primary esophageal adenocarcinoma in a 64-year-old man is reported. An ulcerating tumor was located in the middle intrathoracic esophagus. Histopathological examination revealed a moderately differentiated adenocarcinoma, which had invaded down to the adventitia. The cancerous tubuli were lined by flattened cuboidal cells with eosinophilic cytoplasm, which were analogous with the esophageal gland ducts and syringoma of the skin. The carcinoma was spread widely in the lamina propria mucosae without intraepithelial neoplastic elements. An immunohistochemical profile of individual cytokeratins and other epithelial markers in the carcinoma was similar to that of the esophageal gland ducts. Barrett's metaplastic epithelium or ectopic gastric mucosa was not found around the tumor. It is strongly suggested that this unique carcinoma is derived from the esophageal gland ducts.     

Colitis cystica profunda indefinite for dysplasia in Crohn disease: A potential diagnostic pitfall

Colitis cystica profunda (CCP) is a nonneoplastic condition characterized by misplaced glands deep to the muscularis mucosae of the colon and may be difficult to differentiate from well-differentiated mucinous adenocarcinoma. Absence of dysplasia in CCP usually aids in this distinction. We present a challenging case of CCP in the setting of Crohn disease (CD) containing foci of atypical epithelium. A right hemicolectomy from a 46-year-old woman contained a stricture associated with a proximal multilocular cystic lesion containing mucin-filled glands dissecting through the colonic wall. These glands had lobulated architecture with smooth contours surrounded by lamina propria and lacking desmoplastic stroma. The epithelium had focal nuclear crowding, enlargement, and hyperchromasia, with increased nucleus to cytoplasm ratio, but overall preserved polarity. Atypical cells were focally positive for CK7 and p53, with increased MIB-1 staining. These findings were interpreted as indefinite for dysplasia. Chronic transmural inflammation and mucosal regeneration probably facilitated epithelial misplacement, which secondarily developed cytologic atypia. However, the overall architecture and lack of dysplasia in the overlying mucosa argue against a diagnosis of adenocarcinoma. Our case illustrates the difficult diagnosis of this uncommon but problematic phenomenon, awareness of which is paramount for pathologists and clinicians participating in the management of CD patients.     

Herniation of mucosal epithelium into the submucosa in chronic ulcerative colitis.

Herniation of the glandular epithelium into the submucosa has been observed in 11 out of 27 cases of chronic ulcerative colitis. Glandular herniation was associated with thickening of the muscularis mucosae, with interruption of the muscularis mucosae by lymphoid follicles, and, in five of the 11 cases, with significant crowding of the glands of the mucosa. This study strongly suggests that sustained contraction of the muscularis mucosae, which has been shown by others to be a major feature of chronic ulcerative colitis, is the prime factor in the formation of downgrowths or herniations of the glandular epithelium into the submucosa. Comparison of the cases in which cancer developed with those where there was glandular herniation led to the conclusion that they are independent associations of chronic ulcerative colitis, and that glandular herniation plays no part in the development of dysplasia or cancer.     

Lymphatic anastomoses between the distal esophagus and gastric cardia in dogs

The intramural lymphatic system draining the distal esophagus and gastric cardia was studied on 35 mongrel dogs, using a dye injection procedure. When the dye was injected into the esophageal or gastric mucosa within 2 cm of the esophago-gastric junction (EGJ), a mesh of lympho-capillary networks was observed advancing inferiorly or superiorly across the EGJ. The intramural lymphatics of the distal esophagus and gastric cardia anastomose, especially in the central part of the muscularis mucosae. On transmission electron microscopy, lumina filled with dye were proved to be lymphatic capillaries by demonstrating open gaps and overlapping or inter-digitating endothelial cell processes. Some lympho-capillaries containing dye were also observed beneath the esophageal epithelium. If the situation be extrapolated to human anatomy, the results suggest that lymphatic neoplastic metastases may occur even in early cases of carcinoma of the distal esophagus or gastric cardia.     

Intramucosal ganglion cells are common in diverticular disease

AIMS: Ganglion cells were thought not to occur within the mucosa of the normal colon and found only in the setting of inflammatory bowel disease and neuronal intestinal dysplasia. The aim of this study was to firmly establish the incidence of intramucosal ganglion cells in diverticular disease, normal mucosa and in a spectrum of gastrointestinal diseases. METHODS: We retrospectively reviewed 50 resection specimens from cases of symptomatic diverticular disease and biopsies and/or resection specimens for several neoplastic and non-neoplastic gastrointestinal diseases (50 normal and 120 cases for a variety of gastrointestinal diseases). Normal cases were constituted by biopsies with no clinical history of large bowel disease and no pathology detected microscopically. RESULTS: All 50 cases of diverticular disease contained intramucosal ganglion cells, located within the muscularis mucosae (49/50 cases) as well as within the lamina propria in nine cases. Intramucosal ganglion cells occurred throughout the colorectum within the muscularis mucosae or lamina propria in normal mucosa in 11 cases and in a further 26 colorectal specimens with Crohn's disease (11/20), ulcerative colitis (11/20), adenocarcinoma (1/20), tubular adenoma (2/20), and mucosal prolapse (1/20). None of the 20 hyperplastic polyps contained intramucosal ganglion cells. CONCLUSIONS: We have firmly established the existence of the intramucosal ganglion cells in normal and diseased colorectum, especially in the mucosa of cases of diverticular disease (100% of cases), Crohn's disease and ulcerative colitis. These three conditions are linked by motility abnormalities which may underlie the reason for the presence of intramucosal ganglion cells.     

Neuerungen in der histologischen WHO-Klassifikation urothelialer Harnblasentumoren und abnormer flacher Urothelläsionen

Recently the World Health Organization published a new classification of urinary bladder tumors which is intended to take into account better the biology of the various lesions and to better distinguish between clearly benign and malignant lesions. We examine the possible diagnostic and clinical impact of the new classification, including recent immunohistochemical findings. Papillary urothelial lesions include papillomas, papillary neoplasms of low malignant potential, and papillary carcinomas. Flat urothelial lesions include hyperplasia, reactive atypia/atypia of unknown significance, dysplasia, and carcinoma in situ. Invasive patterns of papillary carcinomas are discussed, with special emphasis on lamina muscularis mucosae substaging. The most important feature of the new classification is its differentiation of two types of low-grade, noninvasive papillary urothelial lesions: papillary neoplasm of low malignant potential vs. papillary carcinoma. Long-term follow-up studies are needed to determine the clinical significance of this differentiation.     

A clinicopathologic study of esophageal 860 benign and malignant lesions in 910 cases of consecutive esophageal biopsies

The author reviewed 910 cases of consecutive esophageal biopsies in the last 15 year in the pathology laboratory of our hospital. There were 693 normal mucosa and benign lesions (76.2%) and 217 malignant lesions (23.8%). No significant changes were recognized in the esophagus in 50 biopsies (5.5%). In benign lesions, the number and frequency (percentages) were as follows: 263 chronic esophagitis (28.9%), 98 heterotopic gastric mucosa (10.8%), 3 heterotopic colonic mucosa (0.3%), 71 glycogenic acanthosis (7.8%), 68 candidiasis (7.5%), 35 benign ulcer (3.8%), 41 squamous papilloma (4.5%), 4 granular cell tumor (0.4%), 1 tubular adenoma (0.1%), 2 cytomegalovirus esophagitis (0.2%), 3 leiomyoma (0.3%), 17 basal cell hyperplasia (1.9%), and 37 Barrett’s epithelium (4%). In malignant lesions, the number and frequency (percentages) were as follows: 53 mild dysplasia (5.8%), 29 moderate dysplasia (3.2%), 31 severe dysplasia (3.4%), 13 carcinoma in situ (1.4%), 68 squamous cell carcinoma (7.5%), 7 primary adenocarcinoma (0.8%), 1 primary signet ring cell carcinoma (0.1%), 4 primary small cell carcinoma (0.4%), 2 primary amelanotic malignant melanoma (0.2%), 1 primary undifferentiated sarcoma (0.1%), 7 gastric cancer invasion (0.8%), and 1 primary adenoid cystic carcinoma (0.1%). In this article, the clinicopathologic features of these esophageal lesions were described.     

超声内镜精准评估肿瘤起源及组织学特征可提高食管平滑肌瘤的手术疗效

目的 探讨超声内镜评估肿瘤起源及组织学特征能否提高内镜下切除食管平滑肌瘤的手术疗效。 方法 回顾性分析2016年1月～2020年6月因食管黏膜下肿瘤于消化内科治疗并经病理证实为平滑肌瘤患者的临床资料。共58例食管平滑肌瘤患者接受术前超声内镜检查评估后进行内镜下切除。统计患者的肿瘤完整切除率、手术时间、住院时长及并发症发生情况。 结果 术前超声内镜提示,平滑肌瘤起源于黏膜肌层39例,固有肌层19例。瘤体平均直径1.50（0.2～6.5）cm,其中20例行内镜黏膜切除术(EMR),32例行内镜黏膜下挖除术(ESE),6例行黏膜下隧道内镜肿瘤切除术(STER)。总体完整切除率为96.6%。平均手术时间为38.29（15～100）min。术后并发症发生率15.5%（9/58）,均经保守治疗后好转。在39例黏膜肌层起源平滑肌瘤中,20例行EMR,19例行ESE,两组患者的肿瘤大小及并发症发生上差异不显著,但EMR组的手术时间及患者术后住院天数明显更短（P<0.05）。在19例固有肌层起源平滑肌瘤中,13例行ESE,6例行STER,两组患者在肿瘤大小、手术时间、术后住院天数及并发症发生上差异均无显著统计学意义。 结论 术前超声内镜精准评估肿瘤起源及组织学特征可提高食管平滑肌瘤手术疗效。     

Variation in the argyrophil cell population of the rectum in ulcerative colitis and adenocarcinoma

Longstanding ulcerative colitis predisposes to carcinoma of the colon. Argyrophil cell hyperplasia has been observed in association with dysplasia and neoplasia in ulcerative colitis. As the argyrophil cell population includes those cells producing enteroglucagon, a hormone thought to stimulate mucosal proliferation, this study was designed to determine whether there was any consistent variation in the argyrophil cell population in longstanding ulcerative colitis. Argyrophil cells were demonstrated by the Grimelius method of silver impregnation in sections of non-tumour bearing mucosa from the rectosigmoid colon of normal bowel, ulcerative colitics with and without tumour, and mucosa adjacent to, and distant from, carcinoma arising in otherwise normal bowel. Cell numbers were expressed as ratios of argyrophil cells per crypt, per mm of epithelium, and per mm of underlying muscularis mucosae. There was marked individual variation within all groups in all parameters. Between groups, the only significant difference was an increase in argyrophil cells per crypt in ulcerative colitis. The significance of this finding is discussed.     

Muscularis mucosae - the forgotten sibling.

Lamina muscularis mucosae sitting beneath mucosal surface of the digestive tract has received little attention to date compared with external smooth muscle layers. Motor activity of the muscularis mucosae shows a great regional and species difference. Autonomic innervation profile is also different from esophagus to colon or between animal species. Intracellular transduction mechanisms for motor activity of the muscularis mucosae are also different from those of external longitudinal and circular muscles or from vascular and airway smooth muscles. Since the submucosal area is a major source for eicosanoid production, abnormality of muscularis mucosae motor activity may link with abnormality of mucosal absorption and secretion functions. Inflammatory bowel diseases such as diarrhea, irritable bowel syndrome and Crohn's disease accompanied with altered motor activity of the muscularis mucosae. Much attention should be attracted to the human muscularis mucosae as a new therapeutic target for inflammatory bowel diseases.