Primary biliary malignant lymphoma clinically mimicking cholangiocarcinoma: a case report and review of the literature

Primary lymphomas of the liver and biliary tract are rare tumors. We describe an unusual case of a diffuse large B-cell lymphoma arising in the extrahepatic bile ducts with local extension to involve the intrahepatic bile ducts. The patient presented solely with obstructive biliary symptoms. The clinical presentation, radiographic studies, and gross findings at surgery suggested that this patient had a Klatskin tumor (cholangiocarcinoma arising at the junction of the left and right hepatic ducts). While rare, the difference in initial patient management emphasizes the importance of including malignant lymphoma in the differential diagnosis of obstructive biliary lesions. Ann Diagn Pathol 5:25-33, 2001.     

Histochemical localization of ouabain-sensitive, K+-dependent p-nitrophenylphosphatase (Na+-K+-ATPase) activity in the submandibular gland of the mouse: effect of androgen, thyroid hormone, or postnatal age

Ouabain-sensitive Na+-K+-ATPase activity was localized histochemically in the submandibular gland of the mouse under various conditions using p-nitrophenylphosphate as substrate at pH 9. In untreated adult males and females, intense staining was seen in the basally striated portions of the epithelial cells lining the excretory and striated ducts. The region of the lateral cell membranes, but not of the apical plasmalemma, also stained. In granular convoluted tubules (GCTs), strong staining was seen only in a narrow band of the basalmost region of the cells; in males this stained region was thinner than in females, and frequently was absent. The baso-lateral margins of acinar and intercalated duct cells gave a very weak reaction. In untreated males, or in females that were treated with dihydrotestosterone, overall staining for the enzyme was always less than in untreated females, due to the diminished reactivity of androgen-stimulated GCT cells and the decreased number of striated ducts. However, in females treated with triiodothyronine, enhanced activity of Na+-K+-ATPase was indicated by stronger staining in all cell types, including the hypertrophied GCT cells. Na+-K+-ATPase activity was undetected in the submandibular glands at birth, but moderate staining was seen in the larger excretory and striated ducts by 5 days of age. From 10 days of age onward, intense staining was seen in the excretory and striated portions of the ramifying duct system. Developing GCT cells could not be distinguished from their precursor cells in the striated ducts until 25 days of age. These data indicate that the salt-handling capacity of the submandibular gland of the mouse varies with both endocrine status and age.     

Cystadenoma and cystadenocarcinoma with mesenchymal stroma of the liver. Immunohistochemical analysis.

Cystadenoma with mesenchymal stroma is a rare neoplasm of the liver that occurs exclusively in young women and has a potential for malignant transformation. A light microscopic and immunohistochemical study of a case of biliary cystadenoma and another of biliary cystadenocarcinoma revealed a range of differentiation of the lining epithelial cells. The lining cells in the cystadenoma resembled the cells of the normal intrahepatic bile ducts. In contrast, the epithelial lining in the case of cystadenocarcinoma had features of intestinal mucosa, including goblet, Paneth, and endocrine cells similar to those found in other mucinous cystic neoplasms of the foregut area. The compact "ovarianlike" mesenchymal stromal cells had immunohistochemical characteristics of myofibroblasts. These are reactive contractile cells that may proliferate in response to the expanding cysts and female hormones, and they differ immunohistochemically from ovarian stromal cells.     

Intraductal papillary neoplasm arising from peribiliary glands connecting with the inferior branch of the bile duct of the anterior segment of the liver

Intraductal papillary neoplasms of the bile duct are generally thought to arise from neoplastic papillary proliferation of epithelial cells lining the bile duct. We herein report a case with findings that strongly suggested that the biliary cystic tumor might have derived from a peribiliary gland. A 69-year-old female was found to have a cystic lesion with intracystic protrusions at the anterior segment of the right hepatic lobe and underwent hepatic anterior segment resection. Fluoroscopy of the resected specimen injected with contrast medium into the cyst revealed a connection between the cystic lesion and the bile ducts. The cyst was multilocular in appearance. On microscopic examination, the cyst was located within the portal tract of the inferior branch of the anterior segment and connected with the inferior branch of the bile duct. The wall of the hepatic cyst lacked an ovarian-like stroma. The tumor was composed of papillary and glandular components, and the tumor cells were similar to gastric foveolar and pyloric gland epithelia and regarded as adenoma. These tumor cells were positive for MUC 5AC, MUC6, and HIK1083. The tumor was finally diagnosed as an intraductal papillary neoplasm of the bile duct (adenoma, gastric type) arising from a peribiliary gland.     

Cystadenoma of the palate: immunohistochemistry of mucins

Cystadenoma is a relatively rare benign epithelial tumor of the salivary glands, and described herein is an additional case. A 51-year-old Japanese man had noticed a mass of the left hard palate 25 years previously. Macroscopically, the resected specimen was a multicystic lesion. Histologically, the tumor was composed of bilayered columnar epithelium with cystic change and partial solid growth of glandular structures with clear cells. The tumor cells had mild cellular atypia, but the tumor lacked papillary growth and a fibrous capsule. Immunohistochemistry was positive for cytokeratins, epithelial membrane antigen, MUC1, MUC4 and MUC6, but negative for myoepithelial markers, MUC2, MUC5AC and MUC5B. Such MUC expression patterns suggested that cystadenoma occurs from excretory ducts.     

Immunohistochemical studies on the poll gland of the dromedary camel (Camelus dromedarius) during the rutting season

The poll glands are subcutaneous exocrine glands located on the back of the neck behind the ears in male camels. The function of poll glands is not well known, though they are thought to play a role during the rutting season. The presence, location and degree of immunolocalization of microfilaments and intermediate filament systems: actin and cytokeratins (Cks) and also S100 protein were studied in the poll glands in sexually mature one-humped camels during the rutting season. These proteins were variably expressed between the epithelia, perialveolar, interalveolar tissue and the periductal tissue. Strong α-smooth muscle actin (α-SMA) immunoreactivity (IR) was displayed by the perialveolar myoepithelial cells, periductal and vascular smooth muscle cells (SMCs), but not in the epithelial cells. Cytokeratin (Ck)-IR was strong in the epithelial lining of the secretory alveoli and excretory ducts, however, the apical blebs of the secretory cells were almost negative. Weak to moderate Ck-IR was observed in the perialveolar myoepithelial cells, but not in the interalveolar tissue or endothelial cells. S100 protein was expressed variably in the epithelial lining of the secretory alveoli. S100-IR was more obvious in the supranuclear region and the apical blebs. Variable reaction was observed in the perialveolar myoepithelial cells, periductal and interductal tissue and endothelial cells.     

Anatomie und Pathologie des intrahepatischen und extrahepatischen Gallengangskarzinoms

Adenocarcinomas of the intra- and extrahepatic bile ducts are rare tumors that begin with malignant transformation of the bile duct epithelia. Intrahepatic cholangiocarcinomas derive from the small bile ducts located proximally to the right and left hepatic ducts. Extrahepatic bile duct carcinomas originate in the right or left hepatic duct, the cystic duct, or the choledochal duct. Tumors located at the bifurcation are called Klatskin tumors. The intrahepatic cholangiocarcinomas are classified according to the TNM classification of liver tumors, while the extrahepatic bile duct tumors have their own TNM classification. Several factors, accompanied by a chronic inflammatory reaction, have been discussed in the etiopathogenesis of these tumors: schistosomiasis, ulcerative colitis with primary sclerosing cholangitis, and inborn bile duct cysts of the liver as a consequence of a disturbance of the ductal plate formation. Over 95% of bile duct tumors are adenocarcinomas. In the nomenclature of precursor lesions a two-grade classification of dysplasia (low-grade versus high-grade) has been found to be more reproducible.     

Differentiated bronchiolar epithelium in alveolar ducts of rats exposed to ozone for 20 months.

The effects of exposure to 1.0 ppm of ozone for twenty months were studied in male Fischer 344 rats. Light microscopic, morphometric, and immunohistological approaches were used to determine the distribution and degree of differentiation of ciliated and nonciliated bronchiolar epithelial (Clara) cells lining alveolar ducts of the central acinus, a primary target of ozone-induced lung injury. Alveolar duct pathways extending beyond the level of the most proximal alveolar outpocketing of terminal bronchioles were isolated in longitudinal profile. The distance that ciliated and nonciliated bronchiolar epithelial (Clara) cells projected down each alveolar duct pathway was determined by placing concentric arcs radiating outward from a single reference point at the level of the first alveolar outpocketing. A high degree of heterogeneity in the magnitude of bronchiolar epithelial cell extension into alveolar ducts was noted for each isolation and animal. Age-matched control animals also demonstrated variation in the degree of bronchiolar epithelial cell extension down alveolar ducts. In animals exposed to ozone, a striking similarity was noted by scanning electron microscopy in the surface characteristics of cells lining both terminal bronchioles and alveolar ducts. The presence of Clara cell secretory protein in cells of bronchioles and alveolar ducts was also detected immunohistochemically and visualized using confocal laser scanning microscopy in the reflectance mode. Well-differentiated ciliated and nonciliated bronchiolar epithelial cells were found lining alveolar septal tips and alveoli up to a depth of 1,000 mu into the pulmonary acinus after 20 months of exposure to ozone. No evidence of inflammation was present in alveolar ducts, suggesting that epithelial cell transformations in alveolar ducts is a natural consequence of lifetime exposures to oxidant gases.     

TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues.

TRAF-4 was discovered because of its expression in breast cancers and is a member of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) family of putative signal-transducing proteins. In vitro binding assays demonstrated that TRAF-4 interacts with the cytosolic domain of the lymphotoxin-beta receptor (LT beta R) and weakly with the p75 nerve growth factor receptor (NGFR) but not with TNFR1, TNFR2, Fas, or CD40. Immunofluorescence analysis of TRAF-4 in transfected cells demonstrated localization to cytosol but not nucleus. Immunohistochemical assays of normal human adult tissues revealed prominent cytosolic immunostaining in thymic epithelial cells and lymph node dendritic cells but not in lymphocytes or thymocytes, paralleling the reported patterns of LT beta R expression. The basal cell layer of most epithelia in the body was very strongly TRAF-4 immunopositive, including epidermis, nasopharynx, respiratory tract, salivary gland, and esophagus. Similar findings were obtained in 12- to 18-week human fetal tissue, indicating a highly restricted pattern of expression even during development in the mammary gland, epithelial cells of the terminal ducts were strongly TRAF-4 immunopositive whereas myoepithelial cells and most of the mammary epithelial cells lining the extralobular ducts were TRAF-4 immunonegative. Of 84 primary breast cancers evaluated, only 7 expressed TRAF-4. Ductal carcinoma in situ (DCIS) lesions were uniformly TRAF-4 immunonegative (n = 21). In the prostate, the basal cells were strongly immunostained for TRAF-4, whereas the secretory epithelial cells were TRAF-4 negative. Basal cells in prostate hypertrophy (n = 6) and prostatic intraepithelial neoplasia (PIN; n = 6) were strongly TRAF-4 positive, but none of the 32 primary and 16 metastatic prostate cancer specimens examined contained TRAF-4-positive malignant cells. Although also expressed in some types of mesenchymal cells, these findings suggest that TRAF-4 is a marker of normal epithelial stem cells, the expression of which often ceases on differentiation and malignant transformation.     

Intraductal oncocytic papillary neoplasm of the liver

A very rare case of intraductal oncocytic papillary carcinoma of the liver is reported. A 63-year-old Japanese man was admitted to our clinic because of abdominal pain and jaundice. Imaging techniques revealed a unilocular cystic neoplasm of 14 cm diameter in the medial segment of the left hepatic lobe. Combined percutaneous and endoscopic retrograde cholangiographies revealed the unilocular cystic neoplasm contained a lot of mucus and communicated with the left segmental intrahepatic bile duct, and that mucus filled the left segmental and hepatic ducts. Left lobectomy was performed. The postoperative course was good, and the patient is free of disease 30 months after operation. Pathological examination revealed that the cavity of the neoplasm was continuous with the left segmental intrahepatic bile duct, and that a lot of mucus was present in the neoplasm, as well as in the left segmental and hepatic ducts. The neoplasm consisted of papillary growth of atypical epithelial cells with oncocytic changes. Atypical goblet cells were also recognized. No invasion into the surrounding liver was noted. Non-tumorous intrahepatic bile ducts near the lesion occasionally showed epithelial dysplasia and contained a lot of mucus. Immunohistochemically, the tumor cells were rich in mitochondria and were immunoreactive for cytokeratins 7, 18 and 19, carbohydrate antigen 19-9, and hepatocyte-specific antigen. Some tumor cells were immunoreactive for pancreatic alpha-amylase and lipase. Ultrastructurally, the tumor cells showed numerous mitochondria and mucus droplets. Intraductal neoplasm communicating with the intrahepatic bile ducts has rarely been reported. The present case suggests that intraductal oncocytic papillary neoplasm, as described in the pancreas, may also occur in the intrahepatic bile ducts, and that such hepatic intraductal neoplasm may express hepatocellular and pancreatic acinar phenotypes.     

Ultrastructural and Immunohistochemical Study of Salivary Duct Carcinoma of the Parotid Gland

A case of salivary duct carcinoma of the parotid gland found in an 81-year-old man was studied by light microscopy, immunohistochemistry, and electron microscopy. Histologically, the tumor was composed of elongated cords of cells and ductal structure with desmoplastic stromal reaction. Tumor cell nests sometimes showed central comedonecrosis. Immuno-histochemically, the tumor cells were positive for cytokeratin and epithelial membrane antigen, and they were negative for S-100 protein and muscle-specific actin. Electromicroscopi-cally, two cell types were identified. The first cell type showed electron-lucent cytoplasm with scant organelles. The second type cell contained numerous mitochondria. Neither acinar nor myoepithelial cell differentiation was observed. These findings suggest that salivary duct carcinoma originates from the interlobular or excretory ducts.     

Malignant fibrous histiocytoma arising in the liver

A unique type of hepatic sarcoma in an adult was composed of pleomorphic fibrohistiocytic cells with benign cystic structures. The malignant mesenchymal component was morphologically similar to malignant fibrous histiocytoma of the soft tissue. The cystic epithelial structures appeared to be formed by the cystic transformation of the entrapped bile ducts and ductules. Malignant fibrous histiocytoma can arise in the liver, but the original architecture of the liver may affect or modify the histologic characteristics of the sarcoma.     

Brunner's glands of the duckbilled platypus (Ornithorhynchus anatinus)

Brunner's glands in the platypus form a lobulated, glandular collar confined to the submucosa of the most distal portion of the stomach. The glands end immediately proximal to the gastrointestinal junction and excretory ducts empty in the region where the stratified squamous epithelium lining the stomach changes abruptly to the intestinal lining epithelium of the duodenum. An individual gland of Brunner is composed of several elongate lobules drained by intralobular ducts which often join to form a single excretory duct. Light and electron microscopic studies have shown the secretory tubules to be comprised of large, pyramidal cells limited basally by a delicate basal lamina. The ergastoplasm, cisternae of which are dilated and contain amorphous material, is associated with numerous ribosomes. In basal and perinuclear regions intercisternal granules and smooth surfaced vesicles are found. Numerous small vesicles found in supranuclear areas apparently form from the smooth membrane portions of ergastoplasm located adjacent to Golgi complexes. Membrane-bound amorphous granules of varying electron density occupy the apical cytoplasm and show a tendency to coalesce before emptying their contents into the adjacent lumen. The intralobular duct system is lined initially by a columnar epithelium which changes to a simple squamous form before the ducts combine to form a short excretory duct lined by stratified squamous epithelium. The epithelium lining the duct system contains relatively few organelles but appears to be engaged in a limited amount of synthesis and release of secretory material. Histochemical studies indicate that both the secretory tubules and the duct system elaborate a neutral mucopolysaccharide.     

Non-neoplastic glandular structures in a benign peripheral nerve sheath tumor

It is a recognized fact that glandular structures sometimes occur in peripheral nerve sheath tumors (PNST). Reports indicate that epithelial potential could be expressed in malignant PNST, while the glands in most benign PNST could be trapped skin adnexa. We present a case of spindle cell tumor with glandular structures. The patient was a 55-year-old man who had a subcutaneous tumor excised. The spindle cell tumor had histological characteristics of neurofibroma. The glandular structures had a pattern of immunohistochemical staining that was similar to that of the secretory coils and excretory ducts of normal eccrine glands. Therefore, the glands were thought to be naturally existing eccrine glands. The glands were completely enclosed within the tumor and not connected to one another; a cluster formation was not observed. The upper portion of tumor included some glands of skin adnexa. The spindle cell tumor may have originated from the nerves distributed around the skin adnexa, and grown to the subcutaneous tissue. The glands may have been left behind rather than have been trapped in the tumor.     

MUCOEPIDERMOID CARCINOMA OF THE LIVER

An autopsy case of mucoepidermoid carcinoma of the liver associated with congenital cysts in a 78-year old man was reported. The liver weighed 1,900 g, and there was a massive tumor of 11 × 10 × 6.5 cm in the left lobe with multiple sero-mucinous cysts. Histologically, the tumor cells consisted of four types of cells: mucus-secreting cells, squamous cells, intermediate cells, and oxyphilic cells. The variety of tumor cells quite resembled that of mucoepidermoid carcinoma of the salivary gland. The sero-mucinous cysts were lined with a single layer of cuboidal or columnar cells and were not communicated with the biliary ducts. Part of the cysts with benign lining cells was in continuity with tumor cells of the intermediate type. Discussion was made on the histogenesis of hepatic mucoepidermoid carcinoma in particular emphasis on the association of the congenital cysts.     

Malignant phyllodes tumor of the prostate: retrospective review of specimens obtained by sequential transurethral resection

A case of malignant phyllodes tumor of the prostate in a 67-year-old man is reported. The patient was referred to a hospital for urinary retention. From material taken at three transurethral resections of the prostate (TURP), a histological diagnosis of benign prostatic hyperplasia was made. However, at the fourth TURP, phyllodes tumor was diagnosed due to the presence of elongated epithelial ducts and proliferating cellular stroma with mitosis and nuclear atypia. Two months later, total cystoprostatectomy was performed. Histologically, the tumor was composed of dysplastic stromal cells and irregularly elongated epithelial ducts. Five months later the patient developed multiple lung and pelvic lymph node metastases and died. This report documents progression to a higher histological grade of prostatic phyllodes tumor documented with sequential pathological findings obtained from four TURP and surgical specimens over about 3 years.     

Immunohistochemical localization of S100 protein in benign and malignant conditions of the breast

A peroxidase--antiperoxidase technique for S100 protein has been applied to 122 breast lesions from 122 patients. These included 35 cases of fibrocystic disease, 16 cases of sclerosing adenosis, 24 cases of papilloma and papillomatosis, 43 intraduct carcinomas, and four intralobular carcinomas. In fibrocystic disease, S100 protein was demonstrable in large amounts in cells between the duct lining cells and the basement membrane of the ducts, being most pronounced in those exhibiting adenosis. Areas of epitheliosis showed scattered positive cells within the ducts with more strongly positive cells around these ducts. Apocrine metaplasia was moderately positive. No S100 protein was demonstrable in the epithelial lining cells of cysts or within the stroma. In sclerosing adenosis individual cells and groups of cells in the fibrous tissue were strongly positive. In papillomatosis and papilloma, the vascular core and epithelium failed to stain, but a discontinuous layer of cells between the epithelium and basement membrane was positive. In intraduct and intralobular carcinoma the tumor cells were uniformly negative, and wherever fibrocystic disease was also present, S100 protein was variably demonstrable. The study corroborated the view that fibrocystic disease and benign proliferative processes of the breast appear to contain cells that correspond to myoepithelial cells, and suggests that S100 protein may serve as a useful marker in the separation of benign proliferative breast lesions from in situ carcinoma.     

Keratin filaments in epithelial cells of the excretory ducts of rabbit submandibular glands--an immunohistochemical and ultraimmunohistochemical study

To clarify the roles of various keratin proteins, the distributions of eight keratin intermediate filament proteins (keratins 7, 8, 10, 13, 14, 18, 19 and 20) in the epithelial cells of the excretory ducts of rabbit submandibular glands were studied immunohistochemically and ultraimmunohistochemically. The epithelia of excretory ducts were composed of columnar cells and basal cells. In the columnar cells, intermediate filaments formed a network at the apical area, that is, an apex network connected with desmosomes. Keratins 7, 18 and 20 were detected in the upper layer of the network and keratins 8, 18 and 20 in the lower layer. The intermediate filaments containing keratin 7 were also connected with hemidesmosomes on the basal side. Keratins 7, 18 and 20 were found throughout the entire cytoplasm of the columnar cells. Keratins 8 and 14 were expressed near the nucleus, forming a ring-like structure around the Golgi apparatus in the columnar cells. In the basal cells, by contrast, the intermediate filaments were concentrated around the nucleus, forming a juxtanuclear network which contained keratin 10. Keratin 13 was detected between the juxtanuclear network and the cell membrane, and was connected with both desmosomes and hemidesmosomes. Kratin 7 filaments were contained throughout the entire cytoplasm of the basal cells. These results suggested that different functional subsets of keratin filaments could be distinguished in the epithelial cells of the excretory ducts of the submandibular glands. In the columnar cells, keratins 7, 8, 18 and 20 play a role in cell-cell contact or cell-matrix contact, and both keratins 8 and 14 seem to be involved in the structure of the Golgi apparatus. In the basal cells, keratin 10 may serve to position and anchor the nucleus within the cell, and keratin 13 plays a role in cell-cell and cell-matrix contacts.     

Multilocular renal cyst. Scanning and transmission electron microscopic observations

A multilocular renal cyst in a boy aged one year and four months is presented, with particular attention being paid to the nature of the epithelial lining cells. Light and transmission electron microscopy showed the cyst to be lined by a single layer of flattened or cuboidal epithelial cells of relatively uniform morphology. Neither embryonic elements nor nephroblastomatous foci were noted in the intervening stroma. The scanning electron microscopy showed hitherto undescribed surface morphological features of the epithelial lining cells: They were characterized by the presence of one or, occasionally two centrally positioned long cilia and by variably oriented microvilli. The observations presented here suggested that the lining cells of the cyst most closely resembled the principal cells of the collecting ducts, especially those located in the inner medulla of the kidney. An unexpected finding was the additional occurrence of a giant bullous lesion in the right lung of this patient.     

Immunohistochemical localization of vitamin B12 R-binder in salivary gland tumors. Implications for cell differentiation

Vitamin B12 R-binder, a specific binding protein for vitamin B12, was studied immunohistochemically in normal and 106 neoplastic salivary gland tissues with a monoclonal antibody against vitamin B12 R-binder (R-binder). In normal salivary glands, R-binder localization was restricted to the ductal systems and to mucous acinar cells; serous acinar cells, myoepithelial cells and stromal connective tissues were consistently negative. Among salivary gland tumors, R-binder was present in 87% of pleomorphic adenomas, 100% of monomorphic adenomas, and 40% of adenoid cystic carcinomas; positivity was observed only on luminal surfaces of small ductular elements, indicating that the components closely related to ductal differentiation were rather small in population. R-binder could be detected both in lacunar and non-lacunar cells within chondroid areas of pleomorphic adenomas, suggesting the possibility that chondroid regions arise from metaplastic changes in ductal epithelial cells. In mucoepidermoid tumors, mucous cells and focal squamous cells exhibited cytoplasmic staining. The staining pattern for R-binder in epithelial components of adenolymphomas showed close similarities to those found in normal large excretory ducts. Two acinic cell tumors and one case each of myoepithelioma and malignant myoepithelioma exhibited negative reactivity for R-binder, showing that these neoplasms are solely composed of tumor cells without the characteristics of ductular differentiation. The immunohistochemical examination of salivary gland tumors, employing a monoclonal anti-R-binder antibody, may have some implications for cellular heterogeneity and differentiation in various tumors.