Proteoglycans detected by monoclonal antibodies in adenoid cystic carcinoma of salivary glands.

Thirty-two cases of adenoid cystic carcinoma (ACC) of the salivary glands were examined immunohistochemically by monoclonal antibodies to proteoglycans (PG) such as chondroitin 6 sulfate (C6SPG), chondrotin 4 sulfate (C4SPG), dermatan sulfate (DSPG), heparan sulfate (HSPG) and keratan sulfate (KSPG) in conjunction with specific enzymatic digestion. The cribriform structure of ACC consisted of basaloid, myoepithelium-derived, and luminal tumor cells. The myoepithelial tumor cells were positive for PG, whereas luminal tumor cells were unstained. Occasional pseudocysts also gave positive staining for PG. Tubular structures consisting of modified myoepithelial cells indicated a high intensity reaction for C6SPG and C4SPG, and a slight one for DSPG, HSPG, and KSPG. Immunodepositions in solid and cluster structures were comparatively light in terms of PG. Basement membrane in ACC stained strongly for C4SPG, slightly for C6SPG, and very slightly for DSPG, HSPG, and KSPG. In ACC, immunohistochemical staining of PG was regularly positive in myoepithelium-derived tumor cells, but was irregular in other types of tumor cells.

Biological characterization of pseudocyst-forming cell lines from human adenoid cystic carcinomas of minor salivary gland origin.

Two cell lines (ACCS and ACCY) were isolated from two individuals with adenoid cystic carcinoma (AdCC) using tissue culture techniques. Both cell lines have similar morphology, i.e., elongated and flattened cells with slender cytoplasmic processes. The two cell lines tend to form pseudocysts, which are a specific architectural feature of AdCC. Coexpression of cytokeratin and vimentin was found in the two cell lines, which occasionally also contained S-100 protein and lactoferrin or lysozyme immunoreactivity. Moreover, ACCS and ACCY displayed potential for the production of a large amount of extracellular matrix including basal lamina components such as fibronectin, laminin, and type IV collagen and glycosaminoglycans which are also part of the basal lamina. These findings suggest that the tumor cells, probably basal or myoepithelial like cells, are responsible for the formation of the peculiar stroma of AdCC consisting of a large amount of collagen-like fibers, basal lamina components, and mucopolysaccharides.

Collagenous spherulosis. A comment on its histogenesis.

Collagenous spherulosis is a benign breast lesion involving lobular acini and ductules consisting of eosinophilic spherules measuring up to 100 mu in diameter. It is a myoepithelial product. We described similar lesions in salivary gland tumors and a benign lymphoepithelial lesion of the parotid gland.

Immunohistochemical localization of carcinoembryonic antigen (CEA) in salivary gland tumors.

Carcinoembryonic antigen (CEA) was first isolated from colonic carcinoma and has been used as a diagnostic marker. CEA has also been observed in a variety of epithelial tumors and normal tissues. In this study, CEA was localized by means of immunohistochemical procedures in benign and malignant salivary gland tumors, as well as in normal parotid gland, indicating that CEA is not a reliable marker for differentiation between benign and malignant salivary gland neoplasms.

Clinical applications of the pathological properties of small cell carcinoma, large cell carcinoma, and adenoid cystic carcinoma of the lung.

Lung cancer has considerable treatment problems, with a poor 5-yr survival rate after surgery. Application of histopathological and immunohistopathological subtyping have proven to be powerful tools for the assessment of prognosis. Results in 33 patients with small cell carcinoma, 44 with large cell carcinoma, and five with adenoid cystic carcinoma of the lung are discussed. The 5-yr survival rates in patients with small cell carcinoma of the oat cell type and intermediate type were 24 and 44%, respectively. Argyrophilic granules and neuron-specific enolase, neuroendocrine markers, were detected more frequently in the oat cell type rather than in the intermediate type. In contrast, keratin, epithelial membrane antigen, and carcinoembryonic antigen, epithelial origin markers, were present more frequently in the intermediate type than in the oat cell type. The 5-yr survival rates with large cell carcinoma of the compact growth type and the loose structure type were 46 and 28%, respectively, based on evidence of morphologically intercellular cohesion. The epithelial origin markers were detectable and more frequent in the compact growth type than in the loose structure type. The growth patterns of adenoid cystic carcinoma are classified as tubular, cribriform, and solid. The solid pattern was the most aggressive with extensive perineural invasion. We propose that the pathological properties of lung cancer should be examined as a prognostic implication of subtyping.

Adenoid cystic carcinoma. A clinicopathologic study with flow cytometric analysis.

Forty-five patients with adenoid cystic carcinoma (ACC) of salivary glands were retrospectively studied to determine the prognostic use of DNA ploidy analysis compared with clinicopathologic features. Nuclear suspensions were prepared from 37 of these tumors by the Hedley technique on paraffin-embedded material. The DNA content was analyzed by flow cytometry after propidium iodide staining. Thirty-five tumors were diploid and 2 were tetraploid. Mean survival was 117 and 52 months for the diploid and tetraploid patients, respectively. The median S-phase fraction (Spf) of the 35 diploid tumors was 4.45%. Of the 17 diploid patients who died of disease, there were 11 tumors with high Spf (greater than 4.45%) and 6 tumors with a low Spf (P less than 0.05 chi-square test). The presence of more than 30% of a solid pattern in the tumor was strongly associated with poor median survival in Kaplan-Meier survival curve analysis (P less than 0.05 log rank test). Grade, stage, recurrence, and metastases were also found to be important prognostic factors. Because few tumors were nondiploid, these results suggest that S-phase fraction analysis may be a more useful prognostic indicator than ploidy classification.

[A case of adenoid cystic carcinoma of the esophagus].

A surgical case of an adenoid cystic carcinoma (ACC) of the esophagus in a 75-year-old man is reported. Histologically, the tumor consisted of an ACC, a squamous cell carcinoma and a small tubular adenocarcinoma. The ACC and the tubular adenocarcinomatous regions in the submucosa and the lamina propria were continuous with the overlying squamous cell carcinoma and atypical squamous epithelium. Immunohistochemically, two types of tumor cells were detected in the ACC. One was found to have EMA-positive epithelial cells whereas the other had actin-positive myoepithelial cells. In the normal esophageal gland, actin-positive cells are found at the periphery of acini and around the layer of epithelial cells in the small duct but they have not been detected in the main duct. These findings suggest that the tumor developed from the small duct and differentiated into two directions: an ACC and a squamous cell carcinoma.

Malignant dermal cylindromas. Do they exist? A morphological and immunohistochemical study and review of the literature.

Malignant dermal cylindromas are very rare. We present a case of multiple cylindromas of the scalp with metastasis to a cervical lymph node. The morphology of the tumour was unusual in that it contained eccrine spiradenoma-like areas and foci of squamous differentiation with keratin formation. The immunohistochemical phenotype of the eccrine spiradenoma-like areas and the metastatic tumour was similar, but different from the areas of typical cylindroma. Although alleged "malignant" cylindromas have been reported, none have been described to have metastasized, whereas metastatic eccrine spiradenoma is well-documented. We reiterate that overlaps between dermal cylindroma and eccrine spiradenoma are more common than has been documented. In the rare event of metastases, it is the eccrine spiradenomatous component that is metastatic. We contend that there is no evidence that pure dermal cylindromas have metastasized.

Establishment of a cell line producing basement membrane components from an adenoid cystic carcinoma of the human salivary gland.

A new cell line has been established from an adenoid cystic carcinoma arising in the submandibular gland of a 63-year-old woman. The cultured epithelial-like cells grew vigorously and adhered together to form a sheet. Immunohistochemical stainings for type IV collagen, laminin and fibronectin were clearly positive in the intercellular matrix and on the surface of the culture cells. Chondroitin 6-sulfate proteoglycan and heparan sulfate were also detected. Ultrastructural studies showed that the cells had abundant rough endoplasmic reticulum and a well-developed Golgi apparatus. Rough endoplasmic reticulum near the cell surface was markedly dilated, and contained material of low electron density. This cell line would be useful for biological and biochemical studies on the mechanisms by which the stromal component is formed.

Basal membrane associated substances in human salivary glands and salivary gland tumours.

Human salivary gland tissue was analysed with respect to the distribution of basal membrane associated substances. Collagen type IV and laminin were studied on the basis of monoclonal antibodies, fibronectin was analysed with polyclonal antibodies. The structure of the basal membrane was well preserved in normal salivary gland tissue. There was a continuous staining of the basal membrane around the acini and the ducts. The labelling for these substances appeared to be associated with the myoepithelial cells. Pleomorphic adenomas exhibited a heterogeneous pattern for the basal membrane substances. Focally, there was an augmentation of collagen IV and laminin, as well as of fibronectin. This was observed in the neighbourhood of myoepithelial like cells. Other parts of pleomorphic adenomas showed an interruption of the basal membrane. Adenoid cystic carcinomas displayed a clear staining of the basal membrane associated substances in the pseudocysts. Stromal trabeculae were stained in an irregular manner. Acinic cell tumours, adenocarcinomas, mucoepidermoid tumours and squamous cell carcinomas (for comparison taken from other regions in the head and neck area) presented a clear destruction of the basal membrane as visualized by antibodies against collagen IV and laminin. The study of the basal membrane substances may be helpful for identifying special features of salivary gland tumours and for grading the amount of invasive behaviour in the malignant tumours.

Adenoid cystic carcinoma of the trachea and main-stem bronchus. A clinical, histopathologic, and immunohistochemical study.

Twelve cases of adenoid cystic carcinoma of the trachea and main-stem bronchus were histologically analyzed, and the results were examined with reference to the growth pattern of the tumor and the prognosis. The tumors were histologically classified into tubular, cribriform, and solid subtypes. Three histologic grades were established: grade I, tumors with tubular and cribriform subtypes but without solid subtype; grade II, tumors with tubular and cribriform subtypes in which the solid subtype comprised less than 20% of the area; grade III, tumors in which the solid subtype comprised more than 20% of the area. Three gross infiltrating types were established: type I, entirely intraluminal; type II, predominantly intraluminal; type III, predominantly extraluminal. In most cases histologic grade correlated with gross tumor type; that is, grades, I, II, and III were grossly types I, II, and III, respectively. The tumors infiltrating along the tracheobronchial wall were of the tubular or cribriform subtype, but not of the solid subtype. In two patients who died of distant metastasis, the histologic studies revealed the solid subtype. Immunohistochemical analysis demonstrated that the tubular subtype was the most differentiated form and the solid subtype, the most undifferentiated form. The histologic subtype of adenoid cystic carcinoma of the tracheobronchial tree was an important factor in the growth pattern of the tumor and the prognosis.

Immunolocalization of keratin proteins in sweat gland tumours by the use of monoclonal antibody.

A total of 34 cases (eccrine poroma: 2, cylindroma: 2, eccrine spiradenoma: 4, syringocystadenoma papilliferum: 1, hydroadenoma papilliferum: 1, clear cell hydroadenoma: 7, mixed tumour: 16) of sweat gland tumours of the skin were described in terms of immunohistochemical distribution of keratins using polyclonal anti-keratin antiserum (TK, detecting 41-56 KDa keratins) and monoclonal antibodies (KL1, 55-57 KDa; PKK1, 40, 45, 52.5 KDa). Keratin expression in eccrine poroma, spiradenoma and syringocystadenoma was similar to that in the ductal segment of normal sweat glands. Cylindroma showed usually slight staining for kertins. Tumour cells of hydroadenomas showed not so prominent staining for any of the keratins; however, histologically, tumour cells indicated marked variation, and the degree of keratin proteins also was different among these histological variants. Mixed tumours of the skin were strongly decorated with anti-keratin antibodies along the luminal surface cells of typical structures, while no staining occurred in outer side cells. Luminal tumour cells may be differentiated from secretory coil cells, whereas outer side cells may have a myoepithelial origin, as outer layer cells found in pleomorphic adenoma of salivary glands.

"Adenoid cystic" carcinoma and adenoid basal carcinoma of the uterine cervix. A study of 28 cases.

Adenoid cystic carcinoma (ACC) and adenoid basal carcinoma (ABC) of the uterine cervix are rare tumors that have often been regarded as a single entity. We studied 28 cases of these neoplasms, with 14 cases in each category. Most patients were over 60 years of age, and there was a high proportion of black women. The majority of the women with ACC presented with postmenopausal bleeding and had an obvious mass on pelvic examination. Despite the tumors' architectural similarity to ACC of the salivary gland, microscopic examination of the cervical carcinomas showed necrosis, a high mitotic rate, and greater nuclear pleomorphism. In all but one of the cases, the tumor cells were negative for S-100 protein on immunoperoxidase staining--a finding that provides evidence against a myoepithelial component. However, S-100-positive dendritic cells were present in the stroma of the tumors and among the neoplastic cells. The patients with ABC were usually asymptomatic, without a gross abnormality of the cervix. Microscopic examination disclosed small nests of basaloid cells, almost always beneath, and often arising from, in situ or small invasive squamous cell carcinomas. In contrast to ABC, ACC was often complicated by local recurrence or distant metastasis. We conclude that ACC of the uterine cervix differs from ACC of salivary gland origin and is also distinct clinically and pathologically from cervical ABC.

[Immunohistochemical detection of growth hormone-releasing factor (GRF) in neuroendocrine tumors]. / Immunhistochemischer Nachweis des Growth hormone-releasing factor (GRF) in neuroendokrinen Tumoren.

We examined formalin-fixed, paraffin-embedded human tumors (42) from autopsies and surgical specimens for the presence of human pancreatic GRF-40 using the unlabeled antibody peroxidase-antiperoxidase method to assess the prevalence of tumors containing GRF, to define their primary sites and cellular derivations, and to correlate clinical and pathological features. Two paragangliomas, 1 pancreatic endocrine tumor, 1 bronchial carcinoid and 1 ganglioneuroma were immunoreactive for GRF. Of the GRF-containing tumors, only one bronchial carcinoid and one paraganglioma were associated with acromegaly.

Expression of cytokeratins and vimentin in salivary gland carcinomas as revealed with monoclonal antibodies.

The expression and distribution of cytokeratins and vimentin in fifteen malignant salivary neoplasms were examined by immunocytochemical techniques using, five monoclonal antibodies (mAbs) against different epitopes of Cytokeratins (CKs) (mAbs PKK1, PKK2, and PKK3, identifying CKs 8, 18 and 19, CKs 7, 17 and 19, and CK 18, respectively) and Vimentin (mAbs V9 and V24). Antibody PKK1 gave strong reactions in all neoplasms showing the similarity of these tumours to other digestive system adenocarcinomas. Three general staining patterns of the neoplasms were recognized with respect to the reactivity of mAbs PKK2, PKK3, and V9. Mucoepidermoid cancer, salivary duct carcinoma and a clear cell carcinoma had a higher relative content of CKs 7, 17 and 19 than of CK 18. Adenoid cystic carcinoma showed the same CK pattern but in the periphery of the tumour cords vimentin was readily detected. In two acinic cell carcinomas, the relative content of CK 18 was higher than that of CKs 7, 17 and 19. Furthermore vimentin was expressed in the tumour cells. However, one mucoepidermoid carcinoma showed vimentin expression and two acinic cell carcinomas were vimentin negative and more reactive for PKK2 than PKK3. Pecularities in CK expression were seen: squamous areas of mucoepidermoid carcinomas were stained by mAb PKK3 although CK 18 is not present in normal squamous epithelia or in squamous cell carcinomas of tongue and skin. In conclusion, the different salivary neoplasms can be distinguished on basis of IFP content. Such a differentiation fits with current theories of histogenesis, i.e. vimentin is seen in tumours presumed to arise from intercalated duct reserve cells, whilst the vimentin negative neoplasms would be expected to arise in excretory duct reserve cells.

Immunohistochemical identification of epithelial membrane antigen in sweat gland tumors by the use of a monoclonal antibody.

A total of 78 cases of adnexal tumors of the skin were examined with the use of monoclonal antibody against epithelial membrane antigen (EMA). The EMA reaction was confined to luminal surfaces and lateral borders of sweat glands, both eccrine and apocrine, being usually absent in ductal segments. Neoplastic lesions of all the adenomatous tumours and mixed tumours of sweat glands showed specifically positive EMA staining of luminal surfaces and lateral borders of tubular, duct-like, and cystic structures. However, solid foci of those tumours were negative for EMA. Tumours of ductal origin, e.g. syringomas and poromas, exhibited positive EMA staining in their plasma membrane, although normal intact keratinocytes did not stain for EMA. Immunohistochemical distribution of EMA in skin adnexal tumours was classified into two types: one in which the luminal surfaces and lateral outer borders were positive, similar to that of the normal secretory coil, and the other in which the plasma membrane of neoplastic cells of ductal origin was positive.

Immunohistochemical distribution of human epidermal growth factor in salivary gland tumours.

Immunohistochemical identification of human epidermal growth factor (hEGF) was carried out in a total of 152 cases of salivary gland tumours, consisting 107 pleomorphic adenomas and their variants, 13 adenolymphomas and 32 adenoid cystic carcinomas. A high percentage of pleomorphic adenomas revealed markedly positive hEGF staining of the luminal surface cells of tubuloductal structures and of modified or neoplastic myoepithelial cells. Clear cells of the tumour showed various reactivities from very slight to strong. Eosinophilic epithelial cells of adenolymphoma gave a positive reaction for hEGF in all the cases, whereas most adenoid cystic adenoma lacked hEGF staining; however some cases showed positive staining of the tumour cells. The immunohistochemical detection of hEGF in most salivary gland tumours suggests this factor to be a possible new marker of salivary glands tumours, and to have a biological role in tumour proliferation.

Pleomorphic adenoma and adenoid-cystic carcinoma of the salivary glands: comparative immunohistochemical patterns.

A series of 20 cases of pleomorphic adenoma and 19 cases of adenoid-cystic carcinoma of the salivary glands, and one case in the mammary location, were investigated regarding immunohistochemical reactivity for Tissue Polypeptide Antigen (TPA), Pre-Keratins, Vimentin, S-100 Protein, and their arrangement pattern of fibronectin. As a whole, the results support the hypothesis of morpho-structural and mainly, onto-histogenetic similarities between these tumours, but they also underline the need for great care in outlining their morpho-functional features, in relation to their different prognoses.

Primary adenoid cystic carcinoma of the esophagus. Report of a case and its histochemical characterization.

A case of primary adenoid cystic carcinoma of the esophagus was reported. A 54-year-old male patient had a tumor in the middle third of the esophagus. Barium swallow and endoscopic examination showed a protruding tumor with a shallow ulceration in its vertex. Histological examination of the surgically removed material revealed that it was largely confined to the submucosal layer, with no metastasis to lymph nodes. The tumor cells presented three distinct patterns: globular nest with irregular cystic spaces, trabecular nest, and true tubule. Electron microscopic study revealed no microvilli or triad along cystic spaces in the globular nests. Histochemical study disclosed that cystic spaces and interstitium were rich in glycosaminoglycans. The luminal surface of the true tubules of the tumor, on the other hand, was characteristically lined by sialomucins. The trabecular type-nests differed from the globular nests in showing GSA-II reactivity and containing abundant retinol-binding protein. These results indicate that the three patterns represented different differentiations of the tumor cells. Twenty-three cases of esophageal adenoid cystic carcinoma were found in the literature from 1950 to 1983 and discussed collectively.