Ripening of the cervix with sodium nitroprusside in nonpregnant women.

OBJECTIVE: Few clinical trials have examined the effects of nitric oxide donors on the human cervix. We address the question of the ultrastructural and clinical effects of topical NO donor on the nonpregnant human cervix. METHODS: Twenty patients admitted to the hospital for hysterectomy were randomly assigned to receive either placebo gel or 1% nitroprusside-based gel into the cervical canal. After surgery, a small biopsy of the cervical canal was taken and analyzed by electron microscopy. Vital parameters were monitored after application. RESULTS: In the placebo group, the connective tissue was normal. In the experimental group, the collagen fibers were widely spaced, and no longitudinal collagen bundles were visible. Macrophages, leukocytes, and activated fibroblasts in treated tissues demonstrated a proinflammatory reaction. Adverse effects were reported in a minority of subjects. No significant changes in blood pressure or in nitrite and nitrate levels were reported. CONCLUSION: In both fertile and postmenopausal women, cervical sodium nitroprusside induced morphologic changes similar to those reported for the ripening process.

Correlation between high intake of glycyrrhizin and myolysis of the papillary muscles: an experimental in vivo study.

The ingestion of large quantities of glycyrrhizin, whether as a drug or a sweetener, is known, in susceptible subjects, to induce a syndrome similar to hypermineralcorticoidism, with bouts of hypertension, hypokaliaemia and rabdomyolysis, sometimes associated with severe renal failure and hypokaliaemia-induced arrythmias. Glycyrrhizin is also known to isomerize into the glycyrrhetic (or glycyrrhetinic) acids 18alpha- and 18beta-. In previous works, we reported that these metabolites cause bouts of hypertension and reduction in diuresis at low doses in the rat. In particular, the alpha isomer causes significant elimination of the calcium ion in the urine. The present findings confirm that 18alpha-glycyrrhetic acid is more toxic than either glycyrrhizin or the beta isomer. Histopathological study of tissue samples taken from rats treated with the alpha isomer also reveal selective damage to the myocardium with oedema, myolysis, apoptosis and blistering of the sarcoplasm. These effects begin to appear in the course of subchronic treatment, they manifest themselves in acute treatment and correlate closely with the electrocardiographic changes recorded in rats acutely treated with 18alpha-glycyrrhetic acid.

Combined neuroendocrine carcinoma of the skin (Merkel cell tumor) and trichilemmal cyst.

We report a case of neuroendocrine (Merkel cell) carcinoma (NC) of the skin, associated with a trichilemmal cyst, showing pagetoid spread into the trichilemmal epithelium. The association of the two lesions may strengthen the hypothesis that NC originates from pluripotent stem cells of adnexal epithelium.

Detection of human herpes virus type 8 DNA sequences as a valuable aid in the differential diagnosis of Kaposi's sarcoma.

The occurrence of human herpes virus type 8 (HHV-8) DNA sequences was evaluated by polymerase chain reaction in 36 cases of cutaneous Kaposi's sarcoma (KS) (classic and associated with the acquired immunodeficiency syndrome) and in 88 pathologic entities that can histologically mimic KS, such as reactive and neoplastic vascular processes and lesions featuring focal or extensive spindle cell pattern. A positive reaction was detected in 16 (70%) of 23 samples of classic KS and 10 (77%) of 13 KS cases related to the acquired immunodeficiency syndrome. In particular, 4 (50%) of 8 samples in the patch stage were found to be positive, whereas in the plaque and nodular stages, HHV-8 DNA sequences were observed in 8 (67%) of 12 and 14 (87%) of 16 cases, respectively. KS cases that had yielded previous negative results were found to be positive for HHV-8 on nested polymerase chain reaction, except two cases of classic KS in the patch stage (6% of the total number of KS, 25% of cases in the patch stage). Reactive and neoplastic vascular processes and cutaneous lesions with a spindle cell component were consistently negative. HHV-8 detection by polymerase chain reaction can represent a valuable method for diagnosing KS, particularly in small skin biopsy samples that might show histologic overlap with non-KS lesions. In early patch stage lesions, however, the diagnostic value of the method is hampered by the occurrence of cases in which HHV-8 sequences are still undetectable.

Epithelioid angiosarcoma of the thyroid. Clinicopathological analysis of seven cases from non-Alpine areas.

Epithelioid angiosarcomas of the thyroid usually develop in people living in Alpine regions, and only rare cases arising in subjects living in nonmountainous areas have been reported. We describe the clinicopathological features of a series of seven cases collected from non-Alpine areas. All patients were adults. The tumours appeared as haemorrhagic, unencapsulated, sometimes cystic nodules. In two cases multinodularity was present. They were composed of large, epithelioid cells, which lined vascular-like spaces or were arranged in solid sheets. Intracytoplasmic lumina containing red blood cells were identified. Neoplastic cells were diffusely positive for factor VIII-related antigen, Ulex europaeus agglutinin, CD31 and keratin peptides. Ultrastructural studies were performed in four cases and showed features of endothelial differentiation. An average follow-up of 3.8 years disclosed that four patients died of disease after a median survival time of 5 months, whereas 3 patients are still alive with no evidence or residual disease 27, 32 and 66 months after thyroidectomy. The good prognosis in these patients appears to be related mainly to the absence of extraglandular tumour spread at the time of surgery.

Primary solitary meningioma of the lung.

Light microscopic, ultrastructural and immunohistochemical features of a case of primary meningioma of the lung are described in this report. The lesion was incidentally discovered in the right lung of a 68-year-old man and treated by lobe resection. No evidence of recurrence or metastasis has been detected 2 years after surgery. The literature is reviewed and the differential diagnosis from other neoplasms presenting as coin lesions in the lung is stressed. Different histogenetical theories and the relation to so-called "minute pulmonary chemodectomas" are discussed.

Nuclear areas in breast cancer: relationship with estrogen and progesterone receptor expression.

The relationship between nuclear area and the expression of estrogen (ER) and progesterone receptors (PR) was evaluated in a series of 66 breast carcinomas (50 primaries, 16 metachronous recurrences). Nuclear measurements were directly performed on touch imprints previously reacted for ER and PR by the immunocytochemical method. Nuclei expressing ER or PR were found to be smaller than negative ones. Moreover, area values of PR+ nuclei overlapped with those of ER+ ones. The pattern of receptor expression co-existence was observed to be closely related to nuclear dimensions, since a significant increase in mean nuclear areas was detected in cells from ER-/PR-tumours, as compared with cells from ER+/PR+, ER+/PR- and ER-/PR+ sub-groups. Nuclear area values were also determined in both steroid receptor-positive and steroid receptor-negative neoplastic cells co-existing in the same breast carcinoma. No significant differences in nuclear area values were found between receptor-positive and receptor-negative neoplastic cells in tumours featuring a positive status for at least one of the steroid receptors (ER+/PR+, ER+/PR- or ER-/PR+). On the contrary, in breast carcinomas characterized by a negative steroid receptor status (ER-/PR-), receptor-negative neoplastic nuclei were significantly larger than receptor-positive ones. It is suggested that heterogeneous steroid receptor expression may be caused by a completely different pathogenetic mechanism in receptor-positive and receptor-negative breast carcinomas.

Expression of MHC class I and class II antigens in primary breast carcinomas and synchronous nodal metastases.

Expression of the major histocompatibility (MHC) class I and class II antigens was studied by immunohistochemistry in a series of 70 primary breast carcinomas and in nodal metastases. In particular, the expression of class I (HLA A-B-C) and class II (DP, DQ and DR) molecules was compared in: a) primary breast cancers devoid of nodal metastases (n = 36) and tumors exhibiting metastatic deposits (n = 34) at the time of surgery, and b) primary breast carcinomas and their corresponding synchronous axillary nodal metastases. Reduced or absent HLA A-B-C antigen expression was seen in approximately 54.3% of primary breast carcinomas, whereas a partial or complete induction of class II products was observed in 18.5% (DQ), 30% (DP) or 48.5% (DR) of the same cases. An almost complete overlap of antigen expression was observed in breast tumors in which no metastases were found by histological examination of axillary nodes and in neoplasms showing histologically-diagnosed synchronous metastases. The reactivity for class I and class II antigens in nodal metastases roughly paralleled that exhibited by corresponding primary tumors. A discordant expression was seen in 11 cases (32%) stained for HLA A-B-C and in 8 (24%), 7 (21%) and 6 (18%) cases assayed for DP, DQ and DR products, respectively. When a discordant expression was detected, either decreased or increased staining patterns were observed in metastases. The finding of overlapping MHC antigenic profiles in the majority of primary breast tumors and nodal metastases casts doubts on the hypothesis that loss of MHC antigens can play an important role in the seeding and growth of metastatic breast carcinoma cells.

Medullary carcinoma of the thyroid gland with sustentacular cell-like cells in a patient with multiple endocrine neoplasia, type IIA. Report of a case with ultrastructural and immunohistochemical studies.

We report a case of a medullary carcinoma of the left lobe of the thyroid gland that occurred in a 57-year-old woman. The patient had undergone surgery for treatment of a bilateral-functioning pheochromocytoma when she was 39 years old. A medullary carcinoma of the thyroid gland and/or a pheochromocytoma had also been diagnosed in other family members. The tumor was composed of cells arranged in nests and large sheets separated by fibrous stroma that contained amyloid deposits. Elongated cells with thin, branched cytoplasmic projections that were strongly reminiscent of sustentacular cells usually found in paragangliomas were seen among the neoplastic cells. Immunohistochemical study showed a diffuse positive reaction for calcitonin and low-weight keratins (CAM 5.2) in neoplastic cells, whereas the sustentacular cell-like cells were positive for S100 protein. The reaction for thyroglobulin was negative. Electron microscopy disclosed large numbers of typical neurosecretory granules in the cytoplasm of tumor cells. The sustentacular cell-like cells showed elongated cytoplasmic processes and lacked neurosecretory granules. We concluded that the finding of sustentacular cell-like cells in a medullary carcinoma of the thyroid gland made its differential diagnosis from paraganglioma more problematic.

Extra-axial chordoma. Report of a case with immunohistochemical study.

A case of extra-axial chordoma arisen in the soft tissues of the posterior thoracic wall is reported. Immunohistochemistry showed coexpression of low molecular weight keratins, vimentin and S-100 protein in neoplastic cells. Although rare, examples of chordomas developing in extra-axial locations are reported in the literature and need be differentiated from other tumors that can mimic their histopathological features, such as myxoid chondrosarcomas.

Metastatic capacity and differentiation in murine melanoma cell lines. A morphometric study.

A morphometric analysis was carried out on electron micrographs of cells of the F1 (low metastatic capacity) and F10 (high metastatic capacity) variant sublines of the murine B16 melanoma, both in in-vitro cultures and in lung-metastatic nodules developed after the intravenous injection of neoplastic cells in syngeneic C57 black male mice. A group of 28 morphometric parameters was derived to describe quantitatively each neoplastic cell profile. No qualitative difference was observed between the two cell lines. The quantitative expression of subcellular organelles was dissimilar in the two sublines, being consistently characterized, both in in-vitro cultured cells and in lung-metastatic colonies, by a significant decrease in the mean values of parameters related to melanosomes in the high metastatic capacity cell line (B16-F10). Moreover, in in-vitro cultured cells, indices describing heterochromatin masses and cytoplasmic membranous compartments displayed statistically significant differences between the two sublines. In this experimental system, an inverse relationship between metastatic capacity and differentiation is detected, since cells with a more aggressive metastatic behavior exhibit a decreased degree of differentiation.

Sclerosing adenosis of the prostate. Report of three cases with electronmicroscopy and immunohistochemical study.

Three cases of rare variant of prostatic adenosis with the features of sclerosing adenosis, an uncommon lesion sometimes confused with prostatic carcinoma, are reported. The lesions consisted of a small, single nodule in prostates otherwise showing typical adenomatous and fibromuscular hyperplasia. The lesions were composed of crowded small glands, small solid nests and individual cells embedded in a cellular stroma. Immunohistochemistry showed that the glands were lined by basal cells positive for the high-weight keratins (EAB-903 and AE-3), a finding which confirms the benign nature of the lesion. S-100 protein and smooth muscle actin were also positive in the same basal cells suggesting myoepithelial differentiation, a character not found in basal cells outside this lesion. This finding was confirmed at ultrastructural level by the finding of numerous thin filaments in the cytoplasm of basal cells. It is important to recognize this lesion in order to avoid confusion with well-differentiated prostatic carcinoma.

A morphometric comparison of subcellular structures between primary breast tumors and their nodal metastases.

A morphometric study of subcellular structures in human primary breast tumors (of the ductal infiltrating type) and their synchronous lymph node metastases was carried out using planimetry and stereology. Each primary neoplasm was compared separately with its axillary metastatic growth in order to detect differences in the quantitative estimates of their subcellular components. A set of 24 morphometric parameters was used to quantitatively describe each neoplastic cell profile. Although some subcellular parameters showed significant differences between the cells of a primary tumor and its metastases, no parameter was found to be consistently altered in all cases. No consistent increase or decrease in the values of the affected parameters was observed in the metastases. More than being due to the expression of a biologically variant (more-or-less differentiated) metastatic phenotype, the differences in stereologic parameters detected in metastatic cells appear to reflect the existence of different functional states of the same cell type.

[Malacoplakia of the testis. Description of a case]. / Malacoplachia del testicolo. Descrizione di un caso.

The histological and ultrastructural features of a case of malakoplakia affecting the testis and the epididymis of a 53-year-old man are described. Light microscopy shows a granulomatous inflammatory process, characterized by the accumulation of large mononuclear cells with abundant granular cytoplasm and PAS-positive calcific intracytoplasmic inclusions (so-called Michaelis-Gutman bodies). On E.M., such inclusions appear as concentric lamellated structures with a mineralized core. Although the pathogenesis of malakoplakia is still unclear, an abnormality of the bacteria-digesting function of tissue macrophages, leading to persistence of phagolysosomes, has been postulated. Malakoplakia of testis is a benign entity, which must be differentiated from neoplastic lesions, especially germ cell tumours, and granulomatous disease such as histoplasmosis, mycobacteriosis and idiopathic granulomatous orchitis.

[Observation of a case of Wells syndrome: ultrastructural study]. / Osservazione di un caso di sindrome di Wells: studio ultrastrutturale.

A new case of Wells' syndrome is reported. Histologically the infiltrate of eosinophils extended to the deep dermis and the subcutaneous fat. The characteristic flame figures are seen in the dermis. Ultrastructurally eosinophils were numerous half of then degranulated. No injury to the vessel walls and collagen bundles were observed. The Authors emphasized that Wells' syndrome is a distinctive entity clinical, on likely autoimmune basis, with multiple triggering factors and peculiar histopathologic but not diagnostic picture.

Application of the avidin-biotin-peroxidase complex (ABC-peroxidase) technique to the identification of human papillomavirus antigens on semithin sections by electron microscopy.

A post-embedding immunohistochemical method using avidin-biotin peroxidase complex (ABC-peroxidase) is described for localizing specific antigens for papillomavirus on semithin sections of human warts fixed and embedded in epoxy resins for conventional electron microscopy. The use of very specific and sensitive antibodies and the etching procedure with a saturated solution of sodium ethoxide appears to give good results. Results indicate that this method applied routinely on semithin sections, before the ultrastructural examination, may be suitable as a screening method for positive cells, which will be further examined by electron microscopy.

Morphometric studies on fine-needle aspirates from follicular proliferative lesions of the thyroid.

A morphometric analysis was carried out on smears of fine needle aspirates obtained from proliferative follicular lesions of the thyroid. Mean values, range as well as histograms of nuclear areas were calculated in histologically-diagnosed cases of non-toxic goiters, follicular adenomas and well-differentiated follicular carcinomas. Mean nuclear areas were found to be significantly higher in carcinomas than in adenomas and in adenomas than in non-toxic goiters. In size-frequency distribution histograms, differences among corresponding classes of the three groups were not statistically significant. Linear discriminant analysis was ineffective in differentiating not only benign from malignant follicular tumors, but also non-toxic goiters from adenomas. Morphometric studies on nuclear areas of thyreocytes in fine needle aspirates do not appear to be able to differentiate between proliferative follicular lesions of the thyroid.

Myxopapillary ependymoma of the sacrococcygeal region. Report of a case.

A case of subcutaneous myxopapillary ependymoma arising in the sacrococcygeal region of a 42-year-old woman is reported. Less than 60 cases of such tumors have so far been described in locations outside the central nervous system. Sacrococcygeal ependymomas are locally aggressive tumors that require a complete and wide surgical excision to prevent recurrences. They tend to metastasize in about 17% of cases.

Melanosis (pigmented melanocytosis) of the prostate gland.

A case of stromal melanosis of the prostate gland is reported. Ultrastructurally, dendritic processes and melanosomes, but no basal lamina were observed in melanin-containing cells. In similar cases, characterized by the diffuse distribution of stromal pigmented melanocytes, the term 'pigmented melanocytosis' rather than 'blue nevus' appears more appropriate.