Immunohistochemistry of folliculo-stellate cells in normal human adenohypophyses and in pituitary adenomas

Summary Presence and distribution of S-100 protein (S-100), neuron-specific enolase (NSE), cytokeratin polypeptides, glial fibrillary acidic protein (GFAP), vimentin, actin, lysozyme and pituitary hormones (prolactin, hGH, ACTH, -FSH, -LH, -TSH, alpha subunit) in folliculo-stellate cells (FSC) were studied in seven normal human pituitary glands and 28 pituitary adenomas using peroxidase-antiperoxidase and the avidin-biotin immunohistochemical techniques. Approximately 5% of the cells of the adenohypophysis were agranular, non-hormon-producing FSC most of which showed a conspicuous and strong reaction with S-100 antibodies but some were, in addition, GFAP- and vimentin-positive. In contrast to endocrine cells (EC), FSC were not decorated by antibodies to NSE or cytokeratins. In addition to supportive functions, these cells, due to their close special relationship to EC, seem to have transport and other metabolic functions yet to be elucidated. By their S-100 reactivity and their distribution FSC are comparable to glial cells of the central and schwann and satellite cells of the peripheral nervous system (PNS) as well as to supportive cells in neuroendocrine organs and related tumors (e.g., pheochromocytomas, paragangliomas, carcinoids). With one exception, S-100 reactive FSC were not found in pituitary adenomas. The immunohistochemical demonstration of S-100 protein in pituitary tissue is, therefore, a reliable aid in the discrimination between adenomas and normal pituitary tissue, particularly in small and poorly preserved specimens. In one adenoma FSC were found in addition to ACTH-producing tumor cells. This seems to be an extremely rare event suggesting a combination tumor.Supported in part by Fonds zur Förderung der wissenschaftlichen Forschung (no. 4708) to H. Denk     

Salivary Intraductal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion

Intraductal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into intercalated duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in intercalated duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraductal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These intercalated-duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial proliferation arranged in cystic, cribriform, and micropapillary architecture, surrounded by an intact myoepithelial cell layer, and were completely intranodal. Of two tumors with tissue available for molecular analysis, one demonstrated a NCOA4-RET fusion and one harbored a STRN-ALK fusion that is novel to IDC. Not only does the intranodal presence of IDC present a challenging differential diagnosis, but the complex nature of this proliferation within lymph node tissue raises questions as to whether the myoepithelial component of IDC is actually non-neoplastic in nature. Furthermore, identification of a STRN-ALK fusion expands the genetic spectrum of IDC and adds to evidence of an emerging role for ALK in salivary gland tumors. Further attention to the nature of the myoepithelial cells and documentation of alternate fusion events in IDC may inform continued discussion about its appropriate classification.     

Case report of Brunner’s gland hyperplasia: A rare “mimic” of malignant pathology

IntroductionBrunner’s gland hyperplasia is a rare, benign lesion of the duodenum. The symptomology can range from asymptomatic (as an incidental finding on endoscopy) to gastrointestinal obstruction or haemorrhage.Case presentationWe report a case of a 60-year-old man presenting with post-prandial vomiting and weight loss. Inpatient evaluation led to the likely diagnosis of a duodenal malignancy for which the patient underwent a laparotomy and proximal duodenectomy.Clinical discussionBrunner’s gland hyperplasia is a rare, benign condition that can be overtreated due to the difficulty in obtaining an accurate pre-operative diagnosis. The literature has been reviewed to discuss the approach to diagnosis.ConclusionThis case highlights the potential for Brunner’s gland hyperplasia mimicking a malignancy.     

The superior laryngeal nerve loop and its surgical implications

Summary Based upon findings from 60 cadavers (120 sides), the incidence of superior laryngeal nerve loop, connecting the cervical sympathetic chain and the superior laryngeal nerve and its branches, the external and internal laryngeal nerve, was 98.3% (118 out of 120 sides). In most cases the loop connected the sympathetic chain and the external laryngeal nerve. The external laryngeal nerve was looped, and not linear as traditionally thought. The loop could be divided into three categories, V-shaped, U-shaped and mixed, and subdivided into 5 types and 17 subtypes according to morphological variation. The loop without exception innervated not only the cricothyroid muscle, but also the thyroid gland. The loop is one of the origins of the thyroid nerve. It seems that for thyroid surgery the loop, when lower in position, should be carefully separated from the superior thyroid vessels before the latter are ligated, in order to preserve a normal nerve supply to the muscle as well as to the part of the gland that remains after surgery.

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L'anse du nerf larynge supérieur, étude anatomique et applications chirurgicales

Résumé La fréquence d'une anse du nerf laryngé supérieur réalisant une anastomose entre la chaine sympathique cervicale et le nerf laryngé supérieur et/ou ses branches (rameau laryngé externe et ingerne), est de 98,3 % (118/120). Ce résultat s'appuie sur l'étude de 60 cadavres. Dans la plupart des cas, l'anastomose se fait entre la chaine sympathique cervicale et le rameau laryngé externe. Ce rameau laryngé externe a un trajet curviligne et non linéaire conformément aux données classiques. Il existe trois catégories d'anses : en "V", en "U" et mixte ; on peut également les subdiviser en 5 types et 17 sous-types en fonction des variations morphologiques. Cette anse innerve constamment non seulement le muscle cricothyroïdien mais aussi la glande thyroïde dont elle fournit une partie de l'innervation. Lors de la chirurgie thyroïdienne, si l'anse est en position basse, les nerfs doivent être soigneusement disséqués et séparés des vaisseaux thyroïdiens supérieurs avant ligature de ces derniers de façon à conserver l'innervation normale du muscle et de la partie restante de la glande.

     

Adrenal Medullary Nodules in Beckwith-Wiedemann Syndrome Resemble Extra-Adrenal Paraganglia

Clues to mechanisms regulating development and tumorigenesis may be provided by studies of unusual diseases. Beckwith-Wiedemann syndrome (BWS) is a rare congenital disorder apparently related to abnormal regulation of insulin-like growth factor-2 (IGF-2) production. IGF-2 mRNA has been previously localized to the chief cells of extra-adrenal paraganglia and to adult, but not fetal, adrenal medulla. Expression of IGF-2 by neuroblastomas has been hypothesized to reflect extra-adrenal paraganglionic differentiation. In the adrenals of a fetus with BWS, we have observed both increased numbers of chromaffin cells and organoid nodules resembling extra-adrenal paraganglia. Immunoreactive IGF-2 was observed in both cell types, but was also observed in chromaffin cells in the normal fetal adrenal. The findings suggest autocrine or paracrine influences of IGF-2 in regulating the number and phenotype of cells derived from sympathoadrenal precursors in the developing adrenal medulla as well as in extra-adrenal paraganglia. These results have implications for the interpretation of data from neuroblastoma studies.     

Unilateral Multicentric Breast Carcinoma Studied by Whole Mammary Gland Serial Sectioning

The incidence and clinicopathologic features of unilateral multicentric breast cancer (UMBC) were studied by mammary gland serial sectioning in 116 cases of clinically defined monocentric breast cancer (MONBC) examined histopathologically at the Nagano Cancer Detection Center. UMBC was defined as: 1) histopathologically discontinuous tumors each with an intraductal spread, 2) at least one tumor-free section separating two tumors, and 3) a large primary tumor and other small secondary tumors. UMBC was detected in 23 of 116 cases (19.8%), all with one secondary tumor. Primary and secondary tumors were located in the same quadrant in 34.8% and in different ones in 65.2%. The secondary tumors were <5 mm in size in 56.5%. Secondary tumors, averaging 8.3 mm in size and 25.5 mm in distance from the primary tumor, were almost exclusively noninvasive carcinomas, including 15 (65.4%) noninvasive ductal carcinomas and several special types. The primary and secondary tumors were of the same histologic type in 3 of 23 cases. UMBC patients averaged 6 years younger than MONBC patients, and the incidence of UMBC tended to be higher in younger patients (p<0.1). UMBC tended to occur more frequently in quadrant with an average histologie tumor size significantly smaller than that in MONBC (p<0.01). The histologie types of the primary tumor in UMBC and MONBC were similar, with common types predominant. Lymph node metastases tended to be slightly more frequent in MONBC. This high incidence of UMBC calls for careful attention when considering breast conserving therapy.     

Heterogeneity of Na+/K+-ATPase from rectal gland of Squalus acanthias is not due to α isoform diversity

 Purified Na⁺/K⁺-ATPase (EC 3.6.1.37) isolated from the rectal gland of Squalus acanthias was characterized in ouabain-binding studies and with respect to isoform(s) of the α peptide. To avoid enzyme inactivation [³H]ouabain equilibrium binding was carried out at 20°C. The heterogeneity of Na⁺/K⁺-ATPase isolated from shark rectal gland was similar in [³H]ouabain binding as previously seen in hydrolytic studies. The binding isotherms were compatible with the existence of a high-affinity (K _dis 0.69 nM) and a low-affinity (K _dis 42 nM) component of 1.46 and 0.79 nmol^.(mg protein)^–1, respectively. In Western blots the α peptide of the enzyme hybridized with an isoform-specific polyclonal antibody raised to an α₃-specific region of the large intracellular domain of rat Na⁺/K⁺-ATPase, but not with the supposed α₃-specific monoclonal antibody MA3-915 with its epitope near the N-terminus. Semi-quantitative analysis of the reaction of the α₃-specific polyclonal antibody with the α peptide from the shark enzyme compared to the reaction with α peptide from rat brain enzyme indicated that this region is not exactly the same in the two species. The α peptide of shark enzyme was not recognized by α₁- or α₂-specific polyclonal antibodies, or by the α₁-specific monoclonal antibodies 3B and F6. The large intracellular domain of Na⁺/K⁺-ATPase from shark rectal gland thus seems to be α₃-like and no α isoform heterogeneity seems able to account for the heterogeneity seen in ouabain binding. Received: 7 August 1998 / Accepted: 6 November 1998     

涎腺腺样囊性癌CKs及MSA免疫组化观察

目的：应用一组抗体探讨涎腺腺样性癌（ＡＣＣ）的免疫组化特征。方法：通过ＡＢＣ免疫组化染色检测了３０例涎腺ＡＣＣ中５４Ｋｄ及６６／５７Ｋｄ细胞角蛋白（ＣＫｓ）的分布。结果：ＡＣＣ基本上由５４Ｋｄ阳性细胞和ＭＳＡ阳性细胞构成,这两类细胞不同比例的肿瘤性增生形成ＡＣＣ的不同组织学构型。结论：ＡＣＣ免疫组化表型与正常省腺组织中的导管／腺泡单位的表型特征相似。     

Role of mesenchymal-epithelial interactions in mammary gland development

The mammary gland is a hormone-target organ derived from epidermis and develops as a result of reciprocal mesenchymal-epithelial interactions. The induction of mammary differentiation from indifferent epidermal cells by mammary mesenchyme implies induction of the complement of hormone receptors characteristic of normal mammary epithelium in cells of the epidermis. Considering the facts that mammary epithelial differentiation is induced by mammary mesenchyme and that certain aspects of hormone response (androgen-induced mammary regression) are inextricably linked to mesenchymal-epithelial interactions, it is evident that the biology of the mammary gland arises from and is maintained via cell-cell interactions. As a corollary, perturbation of stromal-epithelial interactions in adulthood may play a role in mammary carcinogenesis and in turn may provide opportunities for differentiation therapy.     

Immunohistochemical analysis of 61 pituitary adenomas with a monoclonal antibody to the neuron-specific β-tubulin isotype

Pituitary adenomas surgically resected from 61 consecutive patients and 9 normal pituitary glands were studied by immunohistochemistry to determine the localization of the class III-tubulin isotype (neuron-specific) which is recognized by the monoclonal antibody TUJ1. In normal pituitary glands only a few cells were weakly immunopositive for TUJ1, whereas, in 43(73%) of 61 adenomas, more than 5% of tumor cells were immunopositive. The result may indicate that this neuron-specific -tubulin isotype may be either expressed de novo or enhanced under the transformation of pituitary acinar cells to tumors.Research fellow of the Department of Pathology, Kitasato University School of Medicine where the work was conducted