Tubular Adenoma of the Gallbladder with Squamoid Spindle Cell Metaplasia:Report of Three Cases with Immunohistochemical Study

Three cases of tubular adenoma of the gallbladder with squamoid spindle cell metaplasia are reported. Two of the three patients, who were middle-aged Japanese, had a solitary polyp in the gallbladder, and the other had three polyps. All the lesions were detected incidentally by ultrasonography. The polyps were pedunculated with a fine or frail stalk, and ranged from 0.5 to 3.9 cm in diameter. Histologically, they were tubular adenomas accompanied by scattered foci composed of a compact collection of short-spindle or oval cells with mild atypia. These cells did not retain intercellular bridges, and lacked intracellular keratinization. Immunohistochemically, the spindle cells stained positively for high-molecular-weight cytokeratin (EAB 903, a marker of squamous cell differentiation), whereas adenoma cells lining the tubules were negative for this antigen. Therefore, the spindle cell component is considered to represent squamoid metaplasia of adenoma cells. Acta Pathol Jpn 41: 41–45, 1991.     

Tubular adenoma of the gallbladder with spindle cell metaplasia.

We report four cases of tubular adenoma of the gallbladder with spindle cell metaplasia. Three patients had solitary polyps in the gallbladder and the fourth had multiple (three) polyps. Only one patient who had a polyp of larger size had abdominal pain. Histologically, these tubular adenomas had characteristic morular foci composed of short spindle cells. These spindle cell components lacked intercellular bridges or cytoplasmic keratinization. Immunohistochemically, the spindle cells stained positively for one or more cytokeratins and negatively for vimentin, muscle actin and S-100 protein. Spindle cells are considered to represent the metaplastic component of the adenoma cells.     

Gastric phenotypic expression in human gallbladder cancers revealed by pepsinogen immunohistochemistry and mucin histochemistry

Summary Gastric phenotypic expression indicated by paradoxical concanavalin A (Con A) staining for class III mucins and the immunoperoxidase method for pepsinogen (Pg) I and Pg II was found in pyloric gland metaplasia of gallbladder epithelium. Using the same methods, the features of gallbladder cancers and their relationship to pyloric gland metaplasia in the human gallbladder epithelium were studied. Histologically, 57 gallbladder cancers were classified into 5 papillary adenocarcinomas, 29 tubular adenocarcinomas, 8 poorly differentiated adenocarcinomas, 6 signet-ring cell carcinomas, 4 mucinous adenocarcinomas, and 5 squamous cell carcinomas. In papillary and tubular adenocarcinomas, Pg I and/or Pg II staining was detected in 80% and 75.9% of cancers, respectively. Pg II staining was significantly more frequent than Pg I staining. One signetring cell carcinoma also had Pg II activity. Pyloric gland metaplasias all contained class III mucins and were further classified into complete type and incomplete type on the basis of presence or absence Pg I and/ or Pg II activities. A few cancer cells with class III mucins were negative for Pg staining; conversely, a few cells with Pg I and/or Pg II had no class III mucins. Phenotypic diversity in both class III mucin reactivity and Pg activities was observed in gallbladder cancer cells with the pyloric gland cell type. By comparison, pyloric gland metaplasia varied only in Pg activities. A few Pg-positive cancers were found in the gallbladder with Pg-negative pyloric gland metaplasia. The present results clearly indicate the appearance of gastric phenotypic expression in both gallbladder epithelium and gallbladder cancers and suggest the independent induction of pyloric gland metaplasia and cancer with gastric phenotypic expression.     

Tubular adenoma with focal squamous metaplasia of the ascending colon

A case of tubular adenoma with focal squamous metaplasia of the ascending colon in a 66-year-old male is reported. The tumor was a pedunculated polyp with a size of 1.5 X 1.4 X 0.9 cm. Histologically, the tumor showed tubular adenoma with moderate to severe atypia, was accompanied by focal squamous metaplasia. It is thought that squamous epithelial polyp may be derived from colonic adenoma with squamous metaplasia, and that the malignant change of colonic adenoma with squamous metaplasia may lead to squamous cell carcinoma, adenosquamous carcinoma, and mucoepidermoid carcinoma. Only seven cases of colonic adenoma with squamous metaplasia have been reported previously in the literature, and it is yet necessary to discuss the histogenesis, significance, and natural history of colonic adenoma with squamous metaplasia.     

Salivary gland components involved in the formation of squamous metaplasia.

Squamous metaplasia is not an uncommon feature of a number of salivary gland lesions. Arterial ligation of rat submandibular and sublingual salivary glands was used for study of the processes and cell types involved in the development of the squamous metaplasia that occurs in ischemic and infarcted portions of gland parenchyma 6 to 8 days following vessel ligation. Light and electron micrographs show that the principal portion of salivary gland tissue undergoing squamous metaplasia is the acinar-intercalated duct cell complex. Early stages of this process involve a gradual dedifferentiation of acinar cells and hyperplasia of acinar, duct luminal cells, and myoepithelium. Subsequently, both luminal and myoepithelial cells have increasing accumulation of tonofilaments and formation of desmosomes, and centrally located cells may undergo keratinization. Immunohistochemical staining of ischemic salivary gland tissue with developing squamous metaplasia was performed with the use of rabbit antisera to human epidermal and Mallory body cytokeratins. The two antisera gave complementary patterns in normal acini and ducts, with antibody to epidermal cytokeratin (ECK) staining only myoepithelial cells and antibody to Mallory body cytokeratin (MBCK) staining mainly luminal epithelial cells. In early phases of squamous metaplasia (6 days after ligation), antibody to ECK stained central and peripheral (myoepithelial) cells, but by 8 days after ligation only central cells were stained. At 6 days after ligation, a proportion of central cells in squamoid clusters stained with antibody to MBCK, and myoepithelial cells were unstained. By 8 days after arterial ligation, cell clusters exhibiting squamous metaplasia were completely unstained with antibody to MBCK, despite the presence ultrastructurally of numerous tonofilament bundles in both types of cells forming these clusters. The propensity for squamous alteration of acinar-intercalated duct complexes has important connotations for salivary gland tumors such as pleomorphic adenoma and mucoepidermoid carcinoma.     

Mesothelioma. Histological and electron microscopic study of human cases

Four cases of mesothelioma were studied histologically and electron microscopically. One of them showed a pure epithelial type of the peritoneal origin, characterised by a tremendous production of hyaluronic acid. The other three tumors originated from the pleura revealed a histology of biphasic type mesothelioma, which showed an admixed tubular and fibrous pattern and consisted of small-sized cells with slight atypia. However, in some places of these tumors they showed considerable atypical features appearing like an anaplastic or squamoid carcinoma and/or spindle cell sarcoma. Hyaluronic acid was histologically demonstrated in the cytoplasmic vacuoles as well as in the luminal space surrounded by the tumor cells. Electron microscopically, varied numbers of microvilli and desmosome-like attachments were found on the surface of the tumor cells. Mitochondria were small and round. Well-developed rERs tended to encircle mitochondria and to dilate forming cisternae. Various amounts of microfilaments were found in the cytoplasm. The tumor cells which were rich in the latter two components, dilated rERs and microfilaments, resembled fibroblasts. Some tumor cells had phagosomes including dense and fine granules similar to ferritin, suggesting their phagocytotic activity. The hyaline matrix, common to the biphasic type tumor which was largely composed of dense collagenous tissues, was demonstrated to contain hyaluronic acid by histochemistry, and it was suggested that some secretory substances of the tumor cell may participate in composing the hyaline matrix to some extent.     

Mixed adenoneuroendocrine carcinoma of the gallbladder with squamous cell carcinomatous and osteosarcomatous differentiation: Report of a case

An extremely rare case of mixed adenoneuroendocrine carcinoma (MANEC) of the gallbladder is reported, in which the tumor showed diverse differentiation toward neuroendocrine tumor (grade 2), tubular adenocarcinoma, squamous cell carcinoma, and, in addition, osteosarcoma. The patient was an 80‐year‐old man, who underwent cholecystectomy because of a large polypoid tumor filling the gallbladder lumen. The tumor consisted of an intimate admixture of neuroendocrine tumor (grade 2) and tubular adenocarcinoma, and, in many areas, cell nests of neuroendocrine tumor appeared to bud off from tubular structures of the adenocarcinoma, in a manner resembling the ‘ductulo‐insular complex’ seen in nesidioblastosis of the pancreas. Small areas of squamous cell carcinoma were also found. The stroma consisted of a dense proliferation of atypical spindle cells showing focal osteosarcomatous differentiation, and an apparent transition from an epithelial tissue component to atypical spindle cells was observed. Immunohistochemically, neuroendocrine cells were positive for synaptophysin, chromogranin A, and serotonin, and the sarcomatoid stroma was partly immunoreactive for cytokeratin. The present case is the first example of MANEC of the gallbladder with simultaneous squamous cell carcinomatous and osteosarcomatous differentiation. ‘Neometaplasia’ of carcinoma cells in diverse directions was considered the most plausible explanation for the formation of this multifaceted neoplasm.     

Histogenesis of Gallbladder Carcinoma from Investigation of Early Carcinoma and Microcarcinoma

Carcinomas of the gallbladder can be grossly divided into two types: carcinoma in adenoma (CIA) and carcinoma without adenoma (CWA). The histogenesis of both types of gallbladder carcinoma (CIA and CWA) was investigated in association with metaplastic changes in 35 early carcinomas larger than 5 mm in diameter and 16 microcar-cinomas up to 5 mm in largest diameter. In five early ClAs and two micro-CIAs, the carcinoma was surrounded by the adenoma, and the areas of both carcinoma and adenoma mainly showed gastric-type metaplasia (GM). On the other hand, 90% of the other 30 early CWAs showed GM and/or intestinal-type metaplasia (IM) in the tumor, and all of them were surrounded by GM and/or IM. Seven of the other 14 micro-CWAs showed GM and/or IM in the tumor as well as in the surrounding mucosa, and had non neoplastic metaplastic glands underneath the carcinoma tissue. The remaining seven micro-CWAs showed no or only mild metaplasia in the tumor and were surrounded by proper mucosa without metaplasia. From these data, it is concluded that carcinoma of CIA possibly arises from adenoma mainly with GM, and that CWA originates either from the upper part of the metaplastic mucosa or from the proper mucosa of the gallbladder. In addition, some CWA may undergo secondary metaplastic changes during tumor growth. Acta Pathol Jpn 39: 235–244, 1989.     

Basal cell adenoma with extensive squamous metaplasia and cellular atypia: a case report with cytohistopathological correlation and review of the literature

Basal cell adenoma (BCA) is a rare benign basaloid neoplasm of the salivary gland. There are four histopathological types of BCA: solid, tubular, trabecular, and membranous. It is known that focal squamous metaplasia may be seen in some BCAs, but it is rare to see extensive squamous metaplasia, especially with cellular atypia. Here, a 25-year-old male with right parotid swelling is presented. Ultrasonography revealed a 2-cm well defined mass in his parotid gland. Fine-needle aspiration (FNA), performed prior to surgical excision, showed a highly cellular tumor composed of basaloid cells, forming small duct-like or tubular structures containing basement membrane-like material, as well as squamous cells with hyperchromatic, enlarged, pleomorphic, and bizzare nuclei. We made a cytopathological diagnosis of "basaloid neoplasm" and also reported that the differential diagnosis included BCA, cellular pleomorphic adenoma, basal cell adenocarcinoma, and carcinoma ex pleomorphic adenoma. The patient underwent total parotidectomy. Both frozen and permanent sections showed a BCA with membranous, tubulotrabecular pattern, and extensive squamous metaplasia. Some of the squamous cells showed significant nuclear hyperchromasia, enlargement, and pleomorphism. As far as we know, this is the first case of BCA with extensive squamous metaplasia and prominent cellular atypia. This case has been presented to show that squamous metaplastic cells with hyperchromatic, enlarged, bizarre, and pleomorphic nuclei can be seen on FNA smears of a benign tumor like BCA. Also, the differential diagnosis of BCA of the salivary gland is discussed here.     

Adenomas of the gallbladder. Morphologic features, expression of gastric and intestinal mucins, and incidence of high-grade dysplasia/carcinoma in situ and invasive carcinoma

We report 201 gallbladder adenomas from 91 patients most of whom were adult females. Fifty-three (58%) patients had gallstones. In 83 (91%) patients the adenomas were single. One gallbladder had 102 adenomas. Histologically, 165 (82%) of 201 adenomas were classified as pyloric, 28 (14%) as intestinal, 5 (2.4%) as foveolar, and 3 (1.4%) as biliary. Two patients had intestinal-type adenomas coexisting with biliary papillomatosis. Twenty-eight percent of pyloric gland adenomas contained squamoid morules. Two pyloric gland adenomas were composed predominantly of columnar oxyphil cells. High-grade dysplasia/carcinoma in situ was identified in 44 (27%) of 165 pyloric gland adenomas and low-grade dysplasia in 25 (15%) of 165. However, only 2 (1%) invasive adenocarcinomas, both of intestinal type, arose in pyloric gland adenomas. Both patients survived more than 5 years. Intestinal-type adenomas were classified as tubular, papillary, and tubulopapillary. High-grade dysplasia/carcinoma in situ was recognized in 13 (46%) of 28 intestinal adenomas. However, only 1 (3.5%) invasive adenocarcinoma with biliary phenotype arose in an intestinal-type adenoma. Foveolar adenomas showed low-grade dysplasia, and biliary adenomas were composed of columnar cells similar to the normal biliary cells of the gallbladder. None of these tumors progressed to adenocarcinoma. MUC5AC and MUC6 labeled 44 (95%) of 46 pyloric gland adenomas, whereas CDX2 was positive in 14 (78%) of 18 intestinal adenomas and MUC2 in 6 (33%) of 18. MUC5AC and MUC6 labeled 2 foveolar adenomas, and 2 biliary adenomas expressed only CK7. The immunophenotype of gallbladder adenomas justifies their classification into pyloric, intestinal, foveolar, and biliary. Our results indicate that adenomas of the gallbladder play a minor role in the pathway of gallbladder carcinogenesis.     

TUBULAR ADENOMA WITH FOCAL SQUAMOUS METAPLASIA OF THE ASCENDING COLON

A case of tubular adenoma with focal squamous metaplasia of the ascending colon in a 66-year-old male is reported. The tumor was a pedunculated polyp with a size of 1.5 × 1.4 × 0.9 cm. Histologically, the tumor showed tubular adenoma with moderate to severe atypia, was accompanied by focal squamous metaplasia. It is thought that squamous epithelial polyp may be derived from colonic adenoma with squamous metaplasia, and that the malignant change of colonic adenoma with squamous metaplasia may lead to squamous cell carcinoma, adenosquamous carcinoma, and mucoepidermoid carcinoma. Only seven cases of colonic adenoma with squamous metaplasia have been reported previously in the literature, and it is yet necessary to discuss the histogenesis, significance, and natural history of colonic adenoma with squamous metaplasia. ACTA PATHOL. JPN. 35 : 507–515, 1985.     

Immunohistochemical metallothionein expression in thymoma: correlation with histological types and cellular origin

Metallothioneins (MTs) are low molecular weight and cysteine-rich intracellular proteins involved in metal homeostasis and detoxication. They are found in certain normal tissues, and are overexpressed in various tumours with correlation to more aggressive behaviour in certain tumours. Since the histopathological types of thymoma have unpredictable invasive potential, MT over-expression was investigated as a possible marker of the invasive potential of thymomas. We studied immunohistochemical MT expression in 27 non-invasive thymomas, 20 micro-invasive thymomas, and 23 macro-invasive thymomas with a mouse monoclonal anti-MT antibody E9 on formalin-fixed paraffin-embedded tissues. MT expression was significantly different among the three groups of thymomas ( P  = 0.02) with a stronger expression in invasive thymomas ( P  = 0.003). However, MT expression was not exclusively limited to invasive thymomas. Therefore, it could not be used as a marker of aggressive potential in individual thymomas. Analysis of MT expression according to the histological types of the thymomas revealed that eight of nine spindle cell thymomas, none of 10 small polygonal cell thymomas, four of 14 mixed thymomas, seven of 29 large polygonal cell thymomas, and seven of eight squamoid thymomas significantly expressed MT. There was a statistically significant difference in MT expression among different histological types of thymomas ( P  = 0.000). The strongest and most consistent expression was observed in spindle cell thymoma and squamoid thymoma. Since spindle cell thymoma was usually non-invasive and squamoid thymoma was more aggressive, MT expression does not correlate with the invasive potential of different histological types of thymomas. But because medullary epithelial cells of the thymus were positive for MT, our results suggest that both spindle cell thymoma and squamoid thymoma might derive from the medullary compartment of the thymus.     

NEPHROGENIC ADENOMA IN FEMALE URETHRA

A case of a 66 years old female who had a nephrogenic adenoma recurring three times during a 6 months course of her illness is reported. With each recurrence, the lesion moved toward the urethral orifice, suggesting an intimate relationship between the recurrent process and physical stimuli to the mucosa. Electron microscopy revealed merely non-specific morphological features of epithelial cells in the lesion.
There were no positive morphological clues in the lesion for supporting the lesion to resemble mesonephric and/or mesodermal tissue. The diagnostic term of tubular metaplasia for the lesion is preferable instead of nephrogenic adenoma.     

胆囊息肉诊断与治疗——25例临床,影像与病理

胆囊息肉是一组胆囊腔内外观形态为息肉样的非结石性占位病变.从病理角度来看,包括真性肿瘤(胆囊癌,单纯性腺瘤,乳头状腺瘤),炎症性息肉、胆固醇性息肉、增生性息肉.本文总结25例胆囊息肉样病变,认为胆囊息肉一经诊断,无论有无临床症状,均应手术切除胆囊.     

Clinicopathological features of duodenal bulb biopsies and their relationship with upper gastrointestinal diseases

AimTo assess the prevalence of the lesions in duodenal bulb mucosa and the relationship between duodenal lesions and upper gastrointestinal diseases, including helicobacter pylori infection.MethodsClinical, endoscopic and pathological data of the cases with duodenal bulb and gastric mucosal biopsy from January 2005 to May 2017 were analyzed retrospectively.ResultsA total of 3540 patients were enrolled. The biopsy from protuberant lesions with endoscopic morphology are mostly duodenal gastric heterotopia or adenoma. The biopsy from duodenal ulcers are often observed in inflammatory changes and gastric metaplasia.Patients with gastric heterotopia had a significantly lower prevalence of chronic atrophic gastritis, intestinal metaplasia, and gastric ulcer; and much higher prevalence of gastroesophageal reflux disease and gastric fundic polyps.Patients with gastric metaplasia had been positively associated with gastroesophageal reflux disease, and negatively associated with gastric fundic polyps.There were positive correlation between helicobacter pylori infection and duodenal active inflammation, Brunner gland hyperplasia, gastric metaplasia and duodenal ulcer. However, Patients with gastric heterotopia in bulb had been negatively associated with helicobacter pylori infection.ConclusionsThe mucosa lesions in duodenal bulb were associated with concurrent gastric fundic gland polyps, gastroesophageal reflux disease, duodenal ulcer, and helicobacter pylori infection.     

Cytological features of basal cell adenocarcinoma of the salivary glands

The cytological features of basal cell adenocarcinoma (BAC) of the salivary gland, a rare carcinoma, have not been well described. This study included patients who were histopathologically diagnosed with BAC and who underwent preoperative fine‐needle aspiration cytological examination. Cytological characteristics, including background, arrangement and shape of the neoplastic cells, nuclear and cytoplasmic features, and presence of stromal spindle cells, were reviewed. Seven patients were enrolled in the study. The cytological specimens were cellular and composed of large or small clusters with occasional discohesive neoplastic cells at the periphery. The predominant cellular morphology was spindle‐shaped in four cases, and small round‐shaped in three cases. These neoplastic cells were tightly packed, showed high cellularity and overlapping nuclei, and had mildly to moderately enlarged round to oval nuclei with occasional small nucleoli and scant cytoplasm. Stromal spindle cells were observed around the basaloid cells in three cases (42.9%). All histology‐proven stromal spindle cell‐positive cases had stromal spindle cells in the cytological specimens. The study findings clearly demonstrate the relatively high frequency of stromal spindle cells in cytological specimens of BAC. This finding is characteristic of BAC, although basal cell adenoma of salivary gland frequently has stromal spindle cells in the cytological specimens. The characteristic that differentiates BAC from basal cell adenoma is the presence of tightly packed and high cellular clusters with discohesive neoplastic cells. An understanding of these cytological features can aid the cytodiagnosis of BAC.     

Morule-like features and tumor-associated lymphoid proliferation in gallbladder carcinoma

A unique case of gallbladder carcinoma with morule-like features and tumor-associated lymphoid proliferation in a 53-year-old man is presented. The surgically resected gallbladder demonstrated a polypoid tumor with a thin stalk, measuring 1.3 x 0.5 cm. Histologically, a well-differentiated tubular adenocarcinoma was accompanied by multiple spindle cell nodules. The stroma of the tumor showed dense lymphocytic infiltrate. Immunohistochemically, the spindled cell nodules were diffusely positive for cytokeratin AE1/AE3 but negative for S-100, NSE, and chromogranin A. The immunohistochemical results considered to be spindle cell nodules were morule-like features. Intranuclear expression of beta-catenin was observed in morule-like features and carcinoma cells. Ki-67 labeling index was 16.7% of carcinoma cells, but Ki-67 immunoreactivity was negative in spindle cell nodules; therefore, morule-like features were considered to represent metaplastic foci of carcinoma cells and not nodular growth of carcinoma cells. Although the exact pathogenesis of marked lymphoid proliferation in the stroma remained unknown, tumor-produced substances may derive from lymphoid proliferation.     

Histochemical studies of metaplastic lesions in the human gallbladder

We studied goblet cell metaplasia and pseudopyloric gland metaplasia in 25 surgically removed, paraffin-embedded gallbladder specimens using mucin histochemistry, silver methods for endocrine cells, and the indirect immunoperoxidase method for 12 peptide hormones, secretory component, and lysozyme. Goblet cell metaplasia was closely related to the occurrence of endocrine cells that showed argentaffinity, argyrophilia, or immunoreactive gastrin, somatostatin, pancreatic polypeptide, or motilin. Mucosal areas without goblet cell metaplasia were devoid of such endocrine cells. Metaplastic pseudopyloric glands showing lysozyme immunoreactivity were positive for class III mucin with paradoxical concanavalin A staining. Specimens with florid metaplastic lesions revealed a low tendency to form Rokitansky-Aschoff sinuses whose cells never showed a metaplastic nature. We compared the pathophysiological significance of metaplastic lesions in the gallbladder with intestinal metaplasia of the stomach.     

Peutz-Jeghers syndrome with osseous metaplasia of the intestinal polyps

A cam of Peutz-Jeghers syndrome (PJS) with osseous metaplasia In three of 15 hamartomatous polyps of the small Intestine Is reported. At 35 years of age, the patient was diagnosed as having PJS by cutaneous pigmentation around the mouth and polyposis of the stomach, duodenum and Intestine. Fifty-two polyps of the large intestine were resected, which were Characteristic of those of PJS. Three of them showed adenomatous and carcinomatous changes, but there was no osseous metaplasia in any of the resected polyps. At age 40, he had surgery under the diagnosis of Intestinal obstruction. There were 15 polyps in the resected jejunum. These polyps were also characteristic of those of PJS. Additionally, three of these polyps were accompanied by osseous metaplasia. Histologically, mature bone formation and Calcification were found close to the hyperplastic glands In the submucosa or in the propriate muscle. Malignant transformation was not observed. Osseous metaplasia is extremely rare in benign potyps, and it has not been reported in hamartomatous polyps of PJS to date. The knowledge of this association may be helpful in the clinical diagnosis of this benign lesion in PJS.     

Pyloric gland-type tubular adenoma superimposed on intraductal papillary mucinous tumor of the pancreas

We report a rare case of pyloric gland-type tubular adenoma of the main pancreatic duct. It was a grossly visible polypoid nodule and was composed of closely packed pyloric-type glands. This adenoma was present within an intraductal papillary mucinous adenoma (IPMA). In this IPMA lesion, aggregations of pyloric-type glands were occasionally observed, and most of the cells including ductal lining cells expressed pyloric gland-type mucin. The IPMA of the present case showed more extensive pyloric gland metaplasia or differentiation than commonly noted in IPMAs. We consider this pyloric gland-type tubular adenoma to be derived from a selective growth of IPMA cells showing pyloric gland metaplasia.