Fine needle aspiration cytologic diagnosis of focal intrahepatic extramedullary hematopoiesis.

A computed tomographic scan in an 80-year-old man with a urinary obstruction demonstrated a solitary space-occupying liver lesion, which was clinically suspected to be a metastatic carcinoma. Fine needle aspiration (FNA) of the mass produced a smear containing atypical, possibly malignant, cells. Correlation of the FNA findings with the patient's history resulted in a cytologic diagnosis of an intrahepatic focus of extramedullary hematopoiesis (EMH). This case shows FNA biopsy to be a reliable method of diagnosing foci of EMH, but also demonstrates the potential pitfall of diagnosing atypical megakaryocytes as malignant in FNA smears. EMH should be considered in the differential diagnosis of patients with bone marrow disorders and mass lesions in extramedullary sites.

Nesidiodysplasia and nesidioblastosis of infancy: ultrastructural and immunohistochemical analysis of islet cell alterations with and without associated hyperinsulinaemic hypoglycaemia.

The pancreata of hyperinsulinaemic, hypoglycaemic infants, having the anatomic anomalies characterised as "nesidioblastosis', were compared with age matched control infants by light microscopy, and electron microscopy. While the hyperinsulinaemic infants showed an apparent increase in total endocrine volume compared with control infants, the light microscopic alterations of topographic maldistribution of endocrine cells, irregularly defined islets and intermingling of endocrine with exocrine elements were common to both hypoglycaemic and control groups. In at least one control case, the total endocrine cell volume was comparable to that seen in hypoglycaemic infants and was not associated with endocrine dysfunction. The ratios of insulin: somatostatin: glucagon cells in hypoglycaemic infants were similar to those of control infants. The results of both immunohistochemistry and electron microscopy gave strong indications of endocrine cells containing more than one immunoreactive peptide and heterogenous granule populations respectively. Ultrastructurally, "composite' cells with features of both exocrine and endocrine differentiation were found with some frequency in two hypoglycaemic infants. These findings are discussed in the light of current notions of gastroentero-pancreatic endocrine system development. We conclude that "nesidioblastosis' as currently defined is not the anatomic substratum of infantile hyperinsulaemic hypoglycaemia. We propose the term "nesidiodysplasia' to encompass the apparently increased and possibly maldistributed and/or malregulated endocrine cells associated with the clinical manifestations of hyperinsulinaemia. The precise relationship between the presumed anatomic abnormalities and abnormal insulin secretion remains to be clarified by further investigations.

Sertoli--Leydig cell tumor with endometroid differentiation. Case report and discussion of histogenesis.

A case of Sertoli-Leydig cell tumor with endometrioid differentiations is reported. The tumor was associated with hirsutism and androgenic excess which normalized following surgical removal. On light-microscopic study, the tumor resembled a well-differentiated endometrioid tumor with luteinized stroma. With further study, the interstitial stromal cell were recognized as Leydig cells, containing scattered Reinke crystals. Tubules and solid cords reminiscent of sex cord elements were also recognized. The dilated glandular elements showed scant apical and luminal positivity with the PAS stain following diastase digestion. Electron-microscopic examination confirmed a dual population of cells, featuring Sertoli-Leydig cell tumor and endometrioid cells. We postulate that this tumor may represent yet another example of multidirectional differentiation.

Neuroendocrine differentiation in basal cell carcinomas.

Ten consecutive cases of basal cell carcinomas were reviewed. Nine of these displayed the typical histology of basal cell carcinoma, the other case was composed of small spindle to ovoid cells with scant cytoplasm and a high mitotic rate, resembling an "oat cell" carcinoma. These were studied using the immunoperoxidase technique for tissue localization of calcitonin, insulin, glucagon, somatostatin, ACTH, gastrin and nerve growth factor. Three cases were negative for all hormones tested. Three cases were focally positive for a single hormone; one each for calcitonin, somatostatin, and ACTH. Two cases were focally positive for ACTH and somatostatin and two cases were focally positive for calcitonin, somatostatin and ACTH. None of the other hormones displayed activity. The positive staining was eliminated after absorption by the specific antigen. This immunohistochemical study illustrated neuroendocrine differentiation in basal cell carcinomas as has previously been suggested by the Grimelius stain and electron microscopy. Thus, as demonstrated in other epithelial neoplasms, basal cell carcinoma may also display neuroendocrine differentiation. This illustrates the potential multidirectional differentiation in neoplastic epithelial cells.

Arias-Stella reaction with prominent nuclear pseudoinclusions simulating herpetic endometritis.

We studied a pronounced Arias-Stella reaction in an incomplete abortion curettage specimen; the gestational age was 8 weeks by size. The majority of cells in this reaction showed ground glass, eosinophilic nuclear "inclusions" simulating herpetic Cowdry type B nuclear inclusions. This was coupled with a history of herpetic stomatitis of the patient and her husband 2 weeks prior to the curettage, raising the question of viremia and transplacental herpetic endometrial infection. Immunoperoxidase staining using the PAP technique directed against Herpes simplex virus types 1 and 2 was negative. Ultrastructural analysis elucidated the true nature of the nuclear "inclusions" as pseudonuclear inclusions consisting of invaginations of cytoplasm within the nuclei. Viral particles were not found. We are unaware of any similar report, and present this case to suggest the possible differential diagnosis between herpetic endometritis with associated cytologic atypia and the Arias-Stella reaction.

Nesidiodysplasia and nesidioblastosis of infancy: structural and functional correlations with the syndrome of hyperinsulinemic hypoglycemia.

Subtotal pancreatectomy specimens of seven infants with persistent hyperinsulinemic hypoglycemia were studied; all showed the characteristic light microscopic picture of nesidioblastosis. Specimens were studied by electron and conventional light microscopy and by light microscopic immunohistochemistry for insulin, glucagon, somatostatin, and HPP (human pancreatic polypeptide); double staining and quantitative methods were also used. Findings were compared with those in age-matched controls. In the hyperinsulinemic hypoglycemic infants, an increase in total endocrine cell volume was found; however, the typical features of nesidioblastosis were also found in the controls. In both groups, immunohistochemistry and electron microscopy suggested that some endocrine cells are capable of producing synchronously more than one hormone. Amphicrine ("composite" or "intermediate") cells with exocrine and endocrine differentiation were found in three hypoglycemic infants. Observations are discussed in relation to current concepts of embryogenesis of the gastroenteropancreative endocrine system. We conclude that nesidioblastosis, as defined anatomically cannot be considered as the morphologic basis of hyperinsulinemic hypoglycemia. The term "nesidiodysplasia" is suggested and includes increased, maldistributed, and malregulated or malprogrammed endocrine and amphicrine cells when associated with endocrine abnormality.

Neuroendocrine carcinomas of the skin: light microscopic, ultrastructural, and immunohistochemical analysis.

Three primary skin carcinomas were analyzed by light microscopy, immunohistochemistry, and electron microscopy. In all cases, local recurrences, regional lymph node metastases, distant metastases, or all three developed. One patient had elevated serum calcitonin levels that did not decrease after thyroidectomy but did return to normal after removal of the skin tumor recurrences, its metastases, or both. The tumor cells were arranged in solid clusters; a trabecular arrangement was occasionally seen. In 2 cases the cells were of intermediate size and showed vesicular central nuclei and pale, moderately abundant cytoplasm. In the remaining case the cells were distinctly smaller and either round or fusiform. Mitoses were more abundant in the latter case than in the former two. By immunohistochemistry, calcitonin- and somatostatin-containing cells were demonstrated in all cases and ACTH in one. By electron microscopy, the cases consisting of intermediate-size cells displayed moderately abundant neurosecretory-type granules irregularly dispersed throughout the cytoplasm. The case consisting of smaller cells displayed fewer and smaller granules that tended to concentrate in slender cytoplasmic processes. We conclude that these tumors constitute parts of the broadening spectrum of neuroendocrine skin carcinomas that may derive from Merkel cells.

Carcinoma of the larynx with mucosubstance production and neuroendocrine differentiation: an ultrastructural and immunohistochemical study.

Primary neuroendocrine tumors of the larynx appear to be extremely rare. We report a case of well-differentiated neuroendocrine carcinoma arising in the larynx of a 61-year-old white woman. This case was initially diagnosed as a lymph node metastasis in the neck from an unknown primary carcinoma. Extensive workup subsequently revealed that the larynx was the primary site of the tumor. An electron microscopic study of both the primary and metastatic tumors showed numerous neurosecretory-type granules. Immunohistochemical studies revealed positive immunoreactivity against calcitonin, somatostatin, and ACTH. However, the tumor also displayed focal exocrine differentiation and mucosubstance production. The patient underwent a supraglottic laryngectomy and radical neck dissection and was free of tumor 22 months postoperatively.

Neuroendocrine carcinomas with multiple immunoreactive peptides and melanin production.

Two primary neuroendocrine skin carcinomas, one bronchial carcinoma, and one typical medullary thyroid carcinoma have been shown by immunohistochemical and electron microscopy to contain two or more immunoreactive peptides as well as melanosomes and premelanosomes. Of the battery of antisera tested, somatostatin was the only material present in all four tumors; calcitonin and ACTH were present in three of the four neoplasms. Neurosecretory granules on the one hand and melanosomes on the other were more readily identifiable in separate cells. However, in at least 2 cases, individual cells were thought to contain both types of structures. Of the various explanations possible, we choose to interpret these tumors as complex neuroendocrine carcinomas comprising cellular populations capable of synchronous production of immunoreactive peptides and melanin. since melanocytes are members of the dispersed neuroendocrine (APUD) system, these observations may not appear entirely surprising. Note-worthy, however, is that melanin synthesis seemingly remains a synchronously available option to neoplastic neuroendocrine cell populations of possibly diverse histogenesis that are actively engaged in the production of multiple hormonal peptides. We consider that these phenomena represent yet another facet of neoplastic multidirectional differentiation. It is possible that the determination of immunoreactive peptides as "markers" may play a future role in the diagnosis, therapy, and prognosis of these and similar tumors and in the study of the dysplasias that may precede them.