B. Frigerio

Merkel cell carcinoma of the skin: the structure and origin of normal Merkel cells

A series of 15 Merkel cell tumours of skin is reported. They occur dominantly on the head and neck and on the extremities of elderly women, frequently presenting as a reddish nodule. Three cases were associated with squamous carcinoma at the same site, an association deserving further study. There are two main patterns: the commoner one takes the form of a trabecular carcinoma in the dermis mimicking metastatic carcinoma, including oat‐cell carcinoma and neuroblastoma: a dissociated‐cell form mimicks malignant lymphymphoma. The triad of vesicular nuclei with very small nucleoli, abundant mitotic activity and apoptosis is so characteristic as to be virtually pathognomonic in conjunction with structural features. Argyrophilia is common, but Bourn fixation is necessary to demonstrate it regularly. Small round secretory granules (89 ± 18 nm) with narrow haloes, and an abundance of intermediate size filaments are among the ultrastructural hallmarks. There is a close similarity between better differentiated tumour cells and normal Merkel cells. The neural crest origin of MC is in doubt both on the basis of studies of the development and regeneration of MC and from the study of Merkel cell tumours.

Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells

It has been found by immunohistochemical staining that antigens normally found in gastric and/or intestinal epithelial cells are expressed in most differentiated duct cell carcinomas of the pancreas. Among 88 such tumors, 93% and 92%, respectively, expressed M1 and cathepsin E, markers of gastric surface-foveolar epithelial cells, 51% expressed pepsinogen II, a marker of gastroduodenal mucopeptic cells, 48% expressed CAR-5, a marker of colorectal epithelial cells, and 35% expressed M3SI, a marker of small intestinal goblet cells. Most of the tumors also expressed normal pancreatic duct antigens; 97% expressed DU-PAN-2, and 59% expressed N-terminus gastrin-releasing peptide. In agreement with these findings, electron microscopy revealed malignant cells with fine structural features of gastric foveolar cells, gastric mucopeptic cells, intestinal goblet cells, intestinal columnar cells, pancreatic duct epithelial cells, and cells with features of more than one cell type. Normal pancreatic duct epithelium did not express any marker of gastrointestinal epithelial cells, whereas such benign lesions as mucinous cell hypertrophy and papillary hyperplasia commonly expressed gut-type antigens but rarely expressed pancreatic duct cell markers. By contrast, lesions characterized by atypical papillary hyperplasia commonly expressed both gastric and pancreatic duct cell markers. Metaplastic pyloric-type glands expressed pepsinogen II and, except for their expression of cathepsin E, were indistinguishable from normal pyloric glands. In marked contrast, the immunohistochemical and ultrastructural features of 14 ductuloacinar cell tumors were those of cells lining terminal ductules, centroacinar cells, and/or acinar cells; none expressed any gut-type antigen. The results indicate that gastrointestinal differentiation is common in both benign and malignant lesions of pancreatic duct epithelium and suggest that duct cell carcinomas are histogenetically related to gastric- and intestinal-type metaplastic changes of epithelial cells lining the main and interlobular ducts of the pancreas.

Characterization of Four Main Cell Types in Gastric Cancer: Foveolar, Mucopeptic, intestinal Columnar And Goblet Cells: An histopathologic, histochemical and ultrastructural study of “early” and “advanced” tumours

Gastrectomy specimens of 148 gastric cancers, 40 of them being intramucosal or microinvasive, 27 penetrating the submucosa and 81 invading the muscularis propria, with or without involvement of the serosa and perigastric tissues, have been investigated with conventional histopathologic techniques, mucin histochemistry and electron microscopy to characterize the various lines of tumour cell differentiation and to correlate these with the histologic patterns of tumour growth. More or less differentiated intestinal columnar, intestinal goblet, gastric foveolar or mucopeptic cells were recognized in most tumours, of glandular, diffuse or mucoid type. Although simultaneous expression of more than one cell type into the same tumour occurred very frequently, intestinal columnar cells were more prominent in tubular adenocarcinomas, goblet cells (especially of colorectal type) in mucoid cancers, mucopeptic cells in diffuse cancers of invasive desmoplastic type and foveolar cells in diffuse cancers of intramucosal signet-ring cell type. In general, an increased tendency to foveolar cell differentiation and a reduced tendency to mucopeptic differentiation has been found in intramucosal cancers as compared to invasive cancers. It is concluded that the type of tumour cell differentiation, which might have some influence on the natural history of gastric cancer, is better related with more defined tumour subtypes than with the usually recognized glandular or diffuse patterns.

The endocrine component of prostatic carcinomas, mixed adenocarcinoma-carcinoid tumours and non-tumour prostate. Histochemical and ultrastructural identification of the endocrine cells.

Two types of endocrine‐paracrine (EP) cells have been detected histochemically and ultrastructurally in normal and hyperplastic prostates; i.e. type 1 cells resembling intestinal EC (enterochromaffin) cells and type 2 cells similar to urethral EP cells previously reported by Casanova et al. (1974). About one‐third of the 40 prostatic carcinomas studied contained EP cells. Four tumours showed a very large number of EP cells: two of these were composite tumours exhibiting both adenocarcinomatous and carcinoid patterns. These four tumours have also been studied histochemically and ultrastructurally. ACTH and β‐endorphin immuno‐reactive cells, ultrastructurally resembling pituitary corticotrophic cells, have been identified in three tumours. Cells identical with type 1 and type 2 cells of the normal prostate were detected in two cases and in a further case, respectively.

Vasoactive intestinal peptide (VIP) cells in the pancreas and gastro-intestinal mucosa - Am Immunohistochemical and ultrastructural study

SummaryUsing antibodies against pure porcine VIP in immunoperoxidase and immunofluorescence tests, VIP-immunoreactive cells have been detected in the pancreas—especially in the islets—and gastrointestinal mucosa of the dog, guinea-pig and man. VIP immunoreactive cells were widely distributed in these tissues, never being numerous at any site. Some parallelism has been noted between such cells and ultrastructurally identified D1 cells of the pancreas and gastrointestinal mucosa. The presence of VIP cells in normal pancreas may help explain the occurrence of pancreatic endocrine tumors producing VIP.

Gastric Carcinoids of Argyrophil ECL Cells

Histochemical and ultrastructural studies were carried out in four gastric carcinoids, two of which were associated with atrophic gastritis and pernicious anemia. All tumors showed intense argyrophilia and vesicular granules resembling those of endocrine enterochromaffinlike (ECL) cells in normal human gastric mucosa. Tumor cells were found to be unreactive to all the 18 available antiserums to gut hormones, including gastrin, somatostatin, glucagon, and pancreatic polypeptides. The tumors were interpreted as ECL cell argyrophil carcinoids with the various degrees of differentiation and atypia.

The endocrine cells of the pancreas and related tumours

Up to seven endocrine cell types have been identified ultrastructurally in the pancreas, including glucagon A cells, insulin B cells, somatostatin D cells, pancreatic peptide F cells and 5-hydroxytryptamine EC cells. In addition, D1 cells, which have been proposed as the cell type producing VIP and possible P cells of unknown function are seen. Various patterns of endocrine cell differentiation have been found in 20 endocrine pancreatic tumours. Well and poorly differentiated B cells have been identified in 6 insulinomas, diagnostic G cells in 3 out of 7 gastrinomas, D1 and/or F cells in 7 diarrheogenic tumours. Moreover, cells apparently unrelated to the prevalent clinical syndrome have been noted in 8 of the 20 tumours. Granular non diagnostic cells (poorly diagnostic gastrin cells? D1 cells?) were particularly frequent in gastrinomas; agranular or poorly granular cells, either of “active” or “stem cell” type, were present in nearly all tumours, particularly in diarrheogenic tumours, gastrinomas and malignant insulinomas. A cytological classification of pancreatic endocrine tumours is proposed.

Histopathology, Cytology and Cytochemistry of Pheochromocytomas and Paragangliomas Including Chemodectomas

The results of histopathological, histochemical and ultrastructural investigations on pheochromocytomas and paragangliomas have been reported. These results allowed the functional identification of the cell types composing many of such tumours. Moreover, comparison of these data with clinico-pathologic findings outlined the advantages and limits of cytologic studies for understanding the natural history of pheochromocytomas and paragangliomas and improving our diagnostic and prognostic criteria.

Histochemical and ultrastructural identification of neurotensin cells in the dog ileum

SummaryIn the dog ileum, neurotensin cells stained with immunofluorescence or immunoperoxidase proved distinct from argentaffin (EC) cells, glucagon immunoreactive (GLI) cells and pancreatic peptide immunoreactive (PP) cells. Neurotensin cells showed various degrees of reactivity with Grimeliussilver. With electron microscopy, besides EC cells, large granule cells with a thin peripheral rim of Grimelius-reactivity (L cells) and large granule cells with variable Grimelius-reactivity of the core (N cells) were found. On distributive grounds, L cells were identified with GLI cells and N cells were interpreted as neurotensin cells.

Primary Polypeptide Hormones and Mucin-Producing Malignant Carcinoid of the Larynx

A case of primary malignant laryngeal carcinoid with dual endocrine and mucous differentiation is reported. Histologically the tumor showed a characteristic organoid pattern and exhibited Alcian-blue, periodic acid-Schiff, and Grimelius silver positivity. By the immunoperoxidase technique calcitonin, ACTH, and alpha-hCG subunit were demonstrated in the tumor cells. Electron microscopy revealed two different types of endocrinelike cells: mucous cells and occasional cells containing both endocrinelike granules and mucin droplets. Diagnostic morphologic criteria of this rare tumor entity are discussed and reference to biologic behavior and possible histogenesis is made.