Electron Microscopic Study of Adenoid Cystic Carcinoma

This ultrastructural study is based on nine cases of adenoid cystic carcinoma arising from the salivary glands. Electron microscopically, the tumors consisted of five cell types: relatively differentiated intercalated duct cells, secretory cells, undifferentiated cells, cells of a squamous nature, and myoepithelial cells. Special attention was paid to the characteristic extracellular substances noted by light microscopic examination of these tumors. The hyaline material of the pseudocysts contained not only mucopolysaccharide granules but also fingerprintlike structures formed by replicated basement membrane. Some of these structures had a dense core, probably composed of mucopolysaccharide granules. Cell islands surrounded by elasticlike material also were found. The true lumina were usually filled with membranovesicular structures originating from fragments of the lining cells, mainly those with squamous differentiation. These membranovesicular structures included electron-dense rods, filamentous whorls, and structures displaying periodicity.     

Use and abuse of frozen section in the diagnosis of follicular thyroid lesions

The role of intraoperative frozen section in certain organ systems such as the thyroid continues to be problematic. In many cases, diagnoses are deferred or nonhelpful—“follicular lesion.” In the modern era, the widespread use of preoperative aspiration biopsy has allowed for more careful selection of patients who undergo thyroid surgery. In many cases, the fine-needle-aspiration (FNA) biopsy diagnosis can be definitive or can guide the specific surgical procedure. The literature supports our approach, which is summarized as follows: Intraoperative consultation is not needed on the intrathyroidal nodule if a preoperative FNA was definitive for papillary carcinoma. Frozen section is of no value in the intraoperative diagnosis of lesions diagnosed on FNA as “follicular neoplasm” or “Hürthle cell neoplasm” because the characterization of these lesions requires detailed analysis of the tumor capsule for the demonstration of capsular and/or vascular invasion—an analysis that is not practical in the intraoperative setting. Finally, intraoperative consultation including frozen section and intraoperative cytologic examination is most useful in those cases that are diagnosed as suspicious for papillary carcinoma by FNA, because the assessment of nuclear features needed for the definitive diagnosis is possible with intraoperative techniques in a significant number of cases.     

Expression of Phaseolus vulgaris leukoagglutinin-binding oligosaccharides in oral squamous cell carcinoma: Possible association with the metastatic potential

The expression of -GlcNAcβ1–6Man-(β1–6) branched oligosaccharides In carcinoma cells has been considered to influence their metastatic potentials. In the present paper, the lectin histochemistry of oral squamous cell carcinomas obtained in biopsy from 34 patients with Phaseolus vulgaris leukoagglutinin (L-PHA), which potentially binds to N-glycosidic carbohydrates with β1–6 linked lactosamin antennae, was studied in order to analyze the relationship between their staining patterns and metastases. The L-PHA-binding oligosaccharides of the carcinomas were expressed on the cell surface in the following patterns: (i) all cells were positive for the staining ('positive'); (ii) some cells were positive but the rest of the carcinoma cells were negative ('weakly positive'); and (iii) all were negative ('negative'). Statistical analysis revealed that the incidence of the metastasis to regional lymph nodes in the 'positive' cases was significantly higher than that in the 'negative' cases. Moreover, the number of the CD14 positive cells including macrophages in the Stroma adjacent to the cardnomas in the 'positive' cases was less than that in the 'negative' or 'weakly positive' cases. The expression of L-PHA-binding oligosaccharides in oral squamous cell carcinoma may be responsible for their metastatic potential to regional lymph nodes, possibly Including their ability to escape macrophage recognition.     

Intra cytoplasmic and Extracytoplasmic Lumina with a Peripheral Halo and Spikes (Spicular Bodies) Found in Epithelial Tumors

Intracytoplasmic lumina, each with a peripheral halo and spikes, a hitherto undescribed histological structure, were found in several human carcinomas. Similar structures found at the free surfaces of carcinoma cells, or those composed of several individual carcinoma cells, were designated extracytoplasmic lumina with a peripheral halo and spikes. Haloes were seen along the cytoplasm around the lumina, and the spikes penetrated into the cytoplasmic haloes. Transmission electron microscopy revealed that these spicular bodies were lumina equipped with microvilli containing an actin core. Spicular bodies were found in the following neoplasms; 22% of hepatocellular carcinomas (11/50), 35% of colonic adenocarcinomas (7/20), 31% of gastric adenocarcinomas (16/51). In contrast, no or only very occasional spicular bodies were found in thyroid (0/20) and mammary (1/22) adenocarcinomas. Although the diagnostic value of this structure is unknown at the present time, its identification in a carcinoma may be a histologic indicator of its endodermal nature. Acta Pathol Jpn 40: 815-819, 1990.     

Graves' disease is associated with an altered CXCR3 and CCR5 expression in thyroid-derived compared to peripheral blood lymphocytes

The mechanisms by which T cells accumulate in the thyroid and support the autoimmune process in patients with Graves' disease (GD) are poorly understood. Chemokines and their receptors may be involved in this process. We have analysed the expression of CXCR3 and CCR5 as Th1-specific chemokine receptors, CCR3 as a marker for Th2 cells, CXCR4 (expressed on unprimed, naive T cells) and CCR2 (known to be involved in autoimmunity) on peripheral blood (PBL) and thyroid-derived lymphocytes (TL) using flow cytometry. Chemokine receptor expression on PBL of GD patients (n = 16) did not differ from that of normal controls (n = 10). In GD, CXCR3+ (67.3 +/- 4.0% versus 45.7 +/- 2.1%) and CCR5+ T cells (42.5 +/- 3.4% versus 18.8 +/- 2.1%) showed a significant enrichment in the TL compared to PBL. The positive cells were contributed mainly by the CD4+CD45R0+ subset. TL are mostly primed CD45R0+ T cells, but surprisingly, they had significantly higher levels of CXCR4+ cells among TL (96.2 +/- 1.0%) compared to PBL (66.8 +/- 4.2%). However, CXCR4 has been induced during in vitro isolation of TL. There was no correlation between chemokine receptors and the level of TSH-receptor and thyroid peroxidase autoantibodies. CCR3+ and CCR2+ cells remained unchanged in TL compared to PBL. We could confirm the results using RT PCR and immunohistology. In summary, TL showed a different chemokine receptor pattern compared to PBL from the same patient. This indicates a role for CXCR3 and CCR5 in the recruitment of T cells to the thyroid in GD.     

The nature of breast dense core granules: chromogranin reactivity

Ultrastructural immunoreactivity for chromogranin with the LK2H10 antibody was examined in nine cases of breast carcinoma and one example of normal resting breast. These tissues were selected for study on the basis of argyrophilia or LK2H10 immunostaining by light microscopy. In two cases, positive reactivity with the chromogranin antibody was seen in breast neuroendocrine-like dense core granules. In a further six cases chromogranin reactivity was not seen in similar granules that showed the neuroendocrine properties of ultrastructural argyrophilia and uranaffinity. Inability to exhibit the full complement of neuroendocrine characteristics in breast carcinomas contrasts with the facility to demonstrate them in tissues of usual neuroendocrine differentiation. Furthermore, in two mucoid carcinomas and one example of normal resting breast ultrastructural cytoplasmic LK2H10 reactivity was evident, which was not localized to dense core granules, although these were present in two of the cases. Our findings demonstrate the heterogeneity of breast dense core granules and discourage acceptance of such characteristics as evidence of histogenesis of these carcinomas from a neuroendocrine cell type in breast tissue.     

Sebaceous Gland and Sweat Gland Carcinomas of the Skin Clinicopathological Study and Significance of c-erbB-2 Oncoprotein Expression

Thirteen sebaceous gland carcinomas and 10 sweat gland carcinomas were examined to elucidate any important histological parameters influencing their prognosis, and the relationship between immunohistochemical expressions of c-erbB-2 oncoprotein and survival of the patients was analyzed. Sebaceous gland carcinomas with vacuolated cytoplasm in more than 50% of whole tumor area, with necrosis, and without lymphoid cell infiltration in tumor nests and stroma had a higher incidence of tumor recurrence and tumor-related death than tumors with vacuolated cytoplasm in 50% or less of whole tumor area (p < 0.01), without necrosis, and with lymphoid cell infiltration in tumor nest and stroma (p < 0.05). Sweat gland carcinomas of all cases with fatal outcomes demonstrated tubular differentiation in 20% or less of whole tumor area, lymphatic permeation and desmoplastic reaction. Three sebaceous gland carcinomas and three sweat gland carcinomas were positive for c-erbB-2 oncoprotein. Two of three sebaceous gland carcinomas, and all three sweat gland carcinomas developed tumor recurrence and ended in tumor-related deaths. Sweat gland carcinomas with c erbB 2 expression had significantly shorter survival than those with negative immunostain (p < 0.01). Cytoplasmic appearance, tumor necrosis, and lymphoid cell infiltration in tumor nests and stroma of sebaceous gland carcinoma, and tubular differentiation, lymphatic permeation, and growth patterns of sweat gland carcinoma are considered to closely correlate to the prognosis. Immunohisto-chemically detected c erbB 2 oncoprotein may be an indicator of bad prognosis. Acta Pathol Jpn 42: 585–594, 1992.     

Expression of ICAM-1, VCAM-1 and ELAM-1 in angiofollicular lymph node hyperplasia (Castleman''s disease): evidence for dysplasia of follicular dendritic reticulum cells

The inducible adhesion molecules mediate important functions in the lymphoid tissues. We have investigated the expression of intercellular adhesion molecule 1 (ICAM-1), endothelial leucocyte adhesion molecule 1 (ELAM-1), vascular cell adhesion molecule 1 (VCAM-1), and platelet endothelial cell adhesion molecule (PECAM/CD31), using immunocytochemistry on cryostat sections of five lymph nodes from patients with Castleman's disease of the hyaline-vascular type. All five cases were characterized by marked hyperplasia of follicular dendritic reticulum cells, which were extensively present even in the mantle zone. Hyperplastic follicular dendritic reticulum cells showed marked expression of VCAM-1, and weak expression of ICAM-1. In two cases, several dysplastic giant cells with aberrant, polyploid nuclei showed aberrant expression of ELAM-1, an endothelium-restricted molecule. Dysplastic giant cells were positive with DRC-1 (an antibody to dendritic reticulum cells), VCAM-1 and occasionally ICAM-1, were negative for the endothelial cell markers factor VIII-related antigen and CD31 and were non-proliferating (Kl-67-). Cells positive for ICAM-1 or VCAM-1 were rare in the interfollicular areas. In all cases vascular hyperplasia was prominent, but endothelial cells were poorly activated in terms of expression of inducible adhesion molecules and of HLA-DR antigens. The possibility that dysplastic follicular dendritic reticulum cells have a pathogenetic role in Castleman's disease is discussed.