The organization of the communication routes between the epithelium and lamina propria mucosae in the human esophagus

Morphological studies examined communication routes between the epithelium and lamina propria mucosae in the human esophagus, using a series of techniques including silver staining, immunohistochemistry, transmission electron microscopy, and scanning electron microscopy (SEM). For SEM, tissue blocks were treated with either osmium/ultrasonication or NaOH. Observations showed the esophageal papillae to be arranged regularly in a mostly longitudinal row. The reticular fibers, consisting of fibrils approximately 40 nm in diameter, were situated just beneath the epithelial basal lamina. They showed a positive reaction with a type III collagen antibody, and formed a continuous sheet 2-3 microm thick with dense networks. This sheet as well as the epithelial basal lamina had numerous foramina of diameters of 3-5 microm. Immune cells such as lymphocytes and Langerhans cells were situated around these foramina. The foramina were situated both around papillae and the duct orifice of the esophageal gland. In addition, lymphoid follicles surrounded the duct of the esophageal gland. The structural characteristics around the duct appear to be those of duct-associated lymphoid tissue (DALT). Thus, these foramina in the epithelial basal lamina and reticular fiber sheet may represent important communication routes between the epithelium and lamina propria mucosae. In addition, they may play an important role in the mucosal immune response in the human esophagus.     

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.     

Cytoarchitecture of the lamina muscularis mucosae and distribution of the lymphatic vessels in the human stomach

The aim of the present study was to clarify the anatomical structure of the lamina muscularis mucosae (LMM) in the human stomach and to correlate it with the lymphatic spread of gastric cancer cells. Human stomachs taken at operation or autopsy were used. The specimens derived from these stomachs were examined by light microscopy immunohistochemistry and scanning electron microscopy (SEM). In the cardia and pyloric wall, bundles of smooth muscle cells of the LMM were relatively loose and thin and formed a reticular configuration. Small lymphatic capillaries (approximately 10–30 μm in diameter) were present directly above the LMM, and relatively large lymphatics (approximately 80–100 μm in diameter) were observed in the submucosal layer and within the LMM. In contrast, the LMM in the fundus, body, and antral wall was composed of tight, thick bundles of smooth muscle cells that ran straight. Large lymphatics were found directly beneath the LMM, but they were few in the lamina propria mucosae. In addition, lymphatics adjacent to veins were also found in the submucosa of the fundus. Structural differences in the LMM of the stomach wall might depend on physiological function. In this study, the relationship between the cytoarchitecture of the LMM or the distribution of lymphatic vessels and cancer invasion is discussed.     

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 x 0.6 x 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.     

The prevalence and character of the muscularis mucosae of the human urinary bladder

We report the results of a histological evaluation of 335 consecutive autopsy specimens of apparently normal urinary bladder for the presence of a complete, partial or minimal muscularis mucosae. There were 164 females (49%) and 171 males (51%), ranging in age from 20 weeks of gestation to 102 years. A muscularis mucosae was present in 117 bladders (35%). The female to male ratio was 2:1, with 45% of female and 25% of male bladders containing a muscularis mucosae. The muscularis mucosae was complete in one case (1%), partial in 23 cases (6%) and minimal in 93 cases (28%). The occurrence of a partial or complete muscularis mucosae was ten times more likely in women than men. The presence of a muscularis mucosae in both women and men was not associated with any known disease process, nor was it related to patient age.     

Thickening of muscularis mucosae in Crohn's disease

Crohn's disease (CD) of the bowel showed a statistically significant thickening of the muscularis mucosae when compared with disease controls. In areas of gross stricture in CD, the muscularis mucosae comprised almost 10% of total wall thickness. Similar findings were also present in a previously characterized experimental model of CD (trinitrobenzene sulfonic acid-induced colitis in rats), particularly in what appeared to be grossly strictured areas. Taken together, these findings suggest that increased mass of muscularis mucosae smooth muscle may be responsible in part for the commonly observed stricture formation in CD. As extreme muscularis mucosae hyperplasia appears to be peculiar to CD, it may serve as an additional marker differentiating CD from other diseases.     

Actual characteristics of the glands distributed in the lamina propria mucosae of the fowl esophagus.

We performed histological and histochemical investigations on the glands distributed in the lamina propria mucosae of the fowl esophagus and demonstrated their actual characteristics. 1. Glandular cells of the compound tubular glands located in the lamina propria mucosae contained a number of fine pepsinogen granules. 2. Reactions to neutral, weak and strong acid mucopolysaccharides, neutral mucus type II and III and sialomucin were evidently positive in these cells. 3. Based on the facts in 1) and 2), we consider that the glands located in the fowl esophagus are undifferentiated gastric glands. 4. The same glands possessed no parietal cells. 5. We demonstrated that the esophageal cardiac glands in the lamina propria mucosae of human esophagus were undifferentiated gastric glands, and they possessed parietal cells. These glands were confirmed in humans alone among the mammalia. 6. The significance of the existence of the same kind of gland in human and fowl esophagus is extremely important. 7. PAS-positive substance in the above-mentioned glands in the fowl esophagus contains sulfuric, acid, neutral mucopolysaccaride and neutral mucus of type II and III but no glycogen. The compound tubular glands distributed in the lamina propria mucosae of the fowl esophagus have been described as mucous glands. We performed histochemical investigation and demonstrated that these glands were undifferentiated gastric glands.     

Phenotypic change of muscularis mucosae in early invasive colorectal adenocarcinoma

BACKGROUND: Invasive colorectal adenocarcinomas have bundles of eosinophilic spindle cells, which are regarded as myofibroblasts, in their desmoplastic stroma, some of which are continuous with the muscularis mucosa. AIM: To investigate the relation between the eosinophilic spindle cells and the muscularis mucosa based on their cytoskeletal phenotypes in early invasive colorectal adenocarcinoma. METHODS: Formalin fixed, paraffin wax embedded tissues of 17 early invasive colorectal adenocarcinomas were immunostained for alpha-smooth muscle actin (alpha-SMA), desmin, and vimentin. RESULTS: The phenotype of the muscularis mucosa was alpha-SMA positive, desmin positive, and vimentin weakly positive, whereas the eosinophilic spindle cells showed a decreased degree of immunoreactivity for alpha-SMA and desmin in particular, and an increased degree of immunoreactivity for vimentin. The degree of phenotypic difference between the muscularis mucosa and the eosinophilic spindle cells was greater in the eosinophilic spindle cells in the centre of the invasive area that were not continuous with the muscularis mucosa than in the eosinophilic spindle cells continuous with the muscularis mucosa. CONCLUSIONS: These findings suggest that the smooth muscle cells of the muscularis mucosa change their phenotype to become eosinophilic spindle cells, namely myofibroblasts, in the early invasive area of colorectal adenocarcinoma.     

The diagnostic value of endoprobe for small esophageal leiomyomas derived from the muscularis mucosae

Esophageal leiomyoma derived from the muscularis mucosae (MM) is a rare condition, and the optimal modality for diagnosis and treatment is controversial. Endoscopic ultrasonography can provide an accurate image of esophageal layer structure, providing information on lesion suitability for potential endoscopic therapy. We attempted to investigate the diagnostic value of a transendoscopic balloon-tipped miniature ultrasonic endoprobe for small esophageal leiomyomas derived from MM. We resected 7 small esophageal leiomyomas derived from MM by endoscopic mucosal resection (EMR), all of which were diagnosed by a balloon-tipped endoprobe. The endosonographic and pathologic features of 7 cases of small esophageal leiomyomas derived from MM were compared. The balloon-tipped endoprobe clearly showed all 7 small esophageal leiomyomas derived from MM, even those under 5 mm in size (smallest lesion, 3.0 mm). The endosonographic characteristics of small esophageal leiomyomas derived from MM were a hypoechoic mass with smooth, regular, and a well-defined outer margin and homogenous inner echogram arising from the second hypoechoic layer. Complete resections were possible in all 7 cases by EMR without any complications. Tumor size was 3.0-13.5 mm (mean 7.8 mm) in maximum diameter. In all cases, endosonographic findings by endoprobe were exactly concordant with pathologic finding in determining the tumors depth in the esophageal wall, tissue origin and characteristics, growth pattern, and size. We detail the balloon-tipped endoprobe is a simple, convenient, and very useful in making accurate diagnosis of small esophageal leiomyomas derived from the MM and the appropriate applications of EMR.     

Limited smoothelin expression within the muscularis mucosae: validation in bladder diverticula

Smoothelin, a marker of differentiated smooth muscle, is diffusely expressed by bladder muscularis propria and is negative to only weakly and focally expressed in muscularis mucosae. We used bladder diverticula, which lack muscularis propria and frequently demonstrate hyperplastic muscularis mucosae, to evaluate the use of smoothelin immunoreactivity in diagnostic pathology. Diverticula from 40 patients (21 with benign features, 19 with neoplastic features) were studied. Immunohistochemistry was performed using smoothelin antibody (clone R4A, 1:150 dilution; Abcam, Cambridge, MA); and tissue was scored as 0 (no expression), 1+ (moderate expression b10% of cells), 2+ expression (moderate expression N10% of cells), and 3+ (robust diffuse expression). All diverticula contained muscularis mucosae of varying caliber; staining in diverticular muscularis mucosae was compared with historic results in the muscularis mucosae of cystectomy specimens. Hyperplastic muscularis mucosae occurred in 31 (78%) of 40 cases. Smoothelin immunoreactivity in the diverticular muscularis mucosae included 0 (16/40, or 40%); 1+ (11/40, or 27.5%); 2+ (13/40, or 32.5%); and 3+ (0/40, or 0%), with a slightly higher 2+ expression level in hyperplastic versus nonhyperplastic muscularis mucosae (35% versus 22%). Adjacent normal muscularis propria, present in 12 specimens, demonstrated 3+ muscularis propria immunoreactivity. Comparison between diverticula with benign and neoplastic features showed no significant difference in smoothelin immunoreactivity. No correlation was evident with smoothelin immunohistochemistry and muscle caliber. Smoothelin immunoreactivity in bladder diverticula confirms the limited nature of smoothelin expression in the muscularis mucosae and represents a useful ancillary technique in the proper histopathologic evaluation of diverticular and nondiverticular bladder carcinomas. A strong and robust staining of smooth, rounded muscle with smoothelin remains a useful diagnostic adjunct in the reliable recognition of muscularis propria.     

Smoothelin is a specific and robust marker for distinction of muscularis propria and muscularis mucosae in the gastrointestinal tract

Montani M, Thiesler T & Kristiansen G
(2010) Histopathology 57 , 244–249 Smoothelin is a specific and robust marker for distinction of muscularis propria and muscularis mucosae in the gastrointestinal tract Aims: As tumour specimens and biopsy specimens become smaller, recognition of anatomical structures relevant for staging is increasingly challenging. So far no marker is known that reliably discriminates between muscularis propria (MP) and muscularis mucosae (MM) of the gastrointestinal tract. Recently, smoothelin expression has been shown to differ in MP and MM of the urinary bladder. We aimed to analyse the expression of smoothelin in the gastrointestinal tract in MP and MM in order to define a novel diagnostic tool to identify MM bundles. Methods and results: The expression of smoothelin was analysed immunohistochemically in comparison with α‐smooth muscle actin (α‐SMA) in specimens from colon, stomach and oesophagus (n = 107). In contrast to α‐SMA, which equally stained MM and MP, absent or significantly weaker smoothelin expression was found in MM was found, which was particularly valid in colon and gastric specimens. Conclusions: The combination of smoothelin and SMA represents a robust marker to discriminate MM from MP in the gastrointestinal tract.     

Anomalous responses to histamine stimulation of guinea-pig oesophageal muscularis mucosae

The incomplete tachyphylaxis of the contractile response to the H₁-stimulants observed on guinea-pig oesophageal muscularis mucosae seems to be H₂-and H₃-antagonist as well as atropine- and tetrodotoxin-resistant. Lidocaine and eserine partially prevented this process probably by a mechanism independent of their main activity. The dualistic antagonism exerted by mepyramine and methysergide on reproducible histamine responses could be explained by a kinetic condition of hemi-equilibrium state together with changes of drug-receptor interaction and by non-specific properties of methysergide. On the whole, the present data indicate that the role of histamine in this tissue has still to be defined.     

Familial autonomic visceral myopathy with degeneration of muscularis mucosae.

An extended family with chronic intestinal pseudo-obstruction which affected 11 of 54 members was studied. Patients presented with recurrent intestinal obstruction in childhood or adolescence: eight of the 11 died before the age of 30. Pedigree analysis showed four consanguineous marriages. The patients were all in the fifth generation and had established an autosomal recessive mode of inheritance. Histological, immunocytochemical, and electron microscopic studies were performed on a colectomy specimen from a surviving affected family member. Familial visceral myopathy was diagnosed--characterised by degeneration and collagenous replacement of both layers of the muscularis propria and the muscularis mucosae.     

Invasive carcinomas of the urinary bladder. Evaluation of tunica muscularis mucosae involvement

Awareness of the existence of a tunica muscularis mucosae in the urinary bladder complicates the assessment of muscle invasive carcinomas on bladder biopsy. Sixty cystectomy specimens and select bladder biopsies were reviewed to analyze this problem. The patterns of development of the tunica muscularis mucosae were categorized as continuous, interrupted, scattered, or absent. Most bladders demonstrated several patterns of development rather than a uniform appearance. The most frequently observed pattern was that of scattered smooth muscle fibers seen in 33 of 40 (82.5%) cases. The rarity of carcinomatous invasion limited to the tunica muscularis mucosae is emphasized. The authors conclude that the potential for overstaging bladder carcinomas because of misinterpretation of this structure is small.     

Morphology of the lamina propria in the human esophagus with special reference to the proprial papillae

The three-dimensional configurations of the proprial papillae in the human esophagus were observed by light microscopy, routine transmission electron microscopy, and scanning electron microscopy combined with NaOH maceration. Numerous finger-like or filiform papillae with a height of about 100m and a width at the base of approximately 30m were clearly distributed in the uppermost proprial layer at approximately equal intervals. The adepithelial surface of the proprial papillae was bordered by a reticular fiber sheet that was stained a deep black color by silver staining. The papillae possessed blood capillaries with fenestration, nerve fibers, and free cells such as lymphocytes, eosinophils, mast cells, and Langerhans-like cells. These findings clearly demonstrate characteristic three-dimensional features of proprial papillae, and their constituent cellular and structural elements in human esophagus.