Spindle-cell non-pleomorphic atypical fibroxanthoma: analysis of a series and delineation of a distinctive variant

Atypical fibroxanthoma is a bizarre, cytologically malignant but usually clinically benign, lesion which typically arises in sun-damaged skin of the head and neck region in the elderly. Classically, its morphology is said to represent the dermal counterpart of pleomorphic malignant fibrous histiocytoma. We have identified 10 cases of a more monomorphic spindle-celled, fascicular variant which, paradoxically, was often mistaken for a clinically malignant lesion because it lacked the pleomorphism of conventional atypical fibroxanthoma. These tumours all arose in the head and neck region as polypoid lesions in the elderly. The tumours were confined to the dermis, often had an epidermal collarette, showed an eosinophilic fascicular morphology and were highly mitotic. All 10 were vimentin positive and five showed very focal actin positivity. Desmin, keratin and S-100 protein were negative in all cases. The clinical course was benign in all cases, justifying their accurate recognition. The principal differential diagnoses are spindle cell squamous carcinoma, spindle cell melanoma and leiomyosarcoma. Immunohistochemistry plays a key role in this distinction.     

Atypical gastric carcinoids

Four examples of infiltrating gastric tumours which had light microscopic features suggestive of carcinoid or oat-cell carcinoma are documented. Histological and ultrastructural findings indicated that these tumours were atypical carcinoids. A spectrum of endocrine cell neoplasia in the stomach analagous to that observed in the bronchus is postulated. It is felt that increased recognition of poorly differentiated endocrine tumours of the stomach might be of prognostic and therapeutic importance.     

Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material

The expression and cellular localization of angiotensin II (Ang II) and AT(1) receptor proteins were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by immunohistochemistry. In the normal prostate, Ang II immunoreactivity was localized to the basal layer of the epithelium and AT(1) receptor immunostaining was found predominantly on stromal smooth muscle and also on vascular smooth muscle of prostatic blood vessels. Ang II immunoreactivity was markedly increased in hyperplastic acini in BPH compared with acini in the normal prostate (normal: 7.4+/-0.2%, n=5 vs. BPH: 22.7+/-1.9%, n=5, p<0.001). However, AT(1) receptor immunoreactivity was significantly decreased in BPH compared with the normal prostate [normal: 16.4+/-2.2%, n=4 vs. BPH: 9.4+/-1.3%, n=5, p<0.05 (p=0.025)]. The present study demonstrates the presence of Ang II peptide in the basal layer of the epithelium and AT(1) receptors on stromal smooth muscle, suggesting that Ang II may mediate paracrine functions on cellular growth and smooth muscle tone in the human prostate. Furthermore, AT(1) receptor down-regulation in BPH may be due to receptor hyperstimulation by increased local levels of Ang II in BPH. These data extend previous findings in support of the novel concept that overactivity of the renin-angiotensin system (RAS) may be involved in the pathophysiology of BPH.     

Correlation between genetic alterations and histopathological subtypes in bronchiolo-alveolar carcinoma and atypical adenomatous hyperplasia of the lung

Bronchiolo-alveolar carcinoma (BAC) is a type of lung adenocarcinoma characterized by growth along the alveolar wall. It is divided into two subtypes: sclerosing BAC (SBAC), which has central fibrosis, and non-sclerosing BAC (NSBAC), which lacks central fibrosis. We compared the genetic alterations in these two types of BAC with those in atypical adenomatous hyperplasia (AAH). There were 39 cases of SBAC, 19 of NSBAC and 20 of AAH. To detect the loss of heterozygosity (LOH) we used the microsatellite markers D3S1234 and D3S1300 on chromosome 3p, IFNA and D9S144 on 9p, and TP53 on 17p. We also used polymerase chain reaction-SSCP analysis and direct sequencing to examine a point mutation of the p53 gene at exons 5-8. At the TP53 locus, the frequencies of LOH showed a statistical rank-difference correlation among AAH, NSBAC and SBAC. On chromosomes 3p and 9p there were no statistical differences of LOH among AAH, NSBAC and SBAC. We detected a significant statistical rank-difference correlation in the p53 mutation among AAH, NSBAC and SBAC. These findings suggest that a process of multistep carcinogenesis from AAH through NSBAC to SBAC might occur in some cases of adenocarcinoma, and LOH of 3p and 9p might be an early event of carcinogenesis, while the p53 mutation might be a later event.     

An Autopsy Case of Metastatic Foci of Hepatocellular Carcinoma in Adenomatous Hyperplasias of the Liver

Adenomatous hyperplasia of the liver is known as a preneoplastic or early developmental stage of hepatocellular carcinoma, in which overt malignant foci occasionally develop. We have recently experienced an autopsy case (a 70-year-old male) of liver cirrhosis with hepatocellular carcinoma and two nodules of adenomatous hyperplasia. The latter two nodules contained several microscopic foci of moderately differentiated hepatocellular carcinoma. There were a number of tumor microemboli in portal vein branches within areas of adenomatous hyperplasia in addition to areas surrounding cirrhotic liver, some of which grew into the parenchyma of adenomatous hyperplasia and cirrhotic regenerative nodules. These findings and the fact that adenomatous hyperplasia contained portal tracts including portal venous branches, suggest that malignant foci in adenomatous hyperplasia of the liver in this case might represent metastases from hepatocellular carcinoma in other parts of the liver via the intrahepatic portal venous system. Acta Pathol Jpn 41: 911 915, 1991.     

Defective functional response to membrane stimuli in lymphocytes from patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a local disturbance in the prostate that may involve an inflammatory infiltrate predominantly composed of activated lymphocytes and macrophages. The activation and proliferative response of T lymphocytes to different mitogenic signals has been analysed in peripheral blood mononuclear cells (PBMC) from 45 patients with BPH and 55 healthy controls. The PBMC obtained from the patients showed a significant specific impairment in proliferation, CD25 expression and IL-2 production in response to stimulation with lectins (phytohaemagglutinin (PHA), concanavalin A (Con A)), that was not corrected by the addition of IL-2 or of phorbol esters (phorbol myristate acetate (PMA)). Also, the CD28 response was defective in patient PBMC. Activation with anti-CD3 or anti-CD2 MoAbs was normal, but the addition of PMA to these stimuli provoked a significant defective response. Only the use of transmembrane stimuli (PMA and ionomycin) elicited responses similar to those found in the control group. The results indicate that peripheral T lymphocytes from BPH patients show a functional impairment that is mainly explained by an alteration of membrane signals (PHA, CD28) and is distal to protein kinase C (PKC) activation.     

Mutations in Steroid 21-Hydroxylase (CYP21)

The inherited inability to synthesize cortisol is termed congenital adrenal hyperplasia. More than 90% of cases are caused by 21-hydroxylase deficiency. This syndrome is characterized by signs of androgen excess and often mineralocorticoid deficiency. Steroid 21-hydroxylase (P450c2l) is a microsomal enzyme expressed in the adrenal gland that catalyzes conversion of 17-hydroxyprogesterone and progesterone to 11-deoxycortisol and deoxycorticosterone respectively. In man, this enzyme is encoded by the CYP21 (CYP21B) gene which is located in the HLA major histocompatibility complex along with a pseudogene, CYP21P (CYP21A). Mutations in CYP21 causing congenital adrenal hyperplasia are almost all generated by recombinations between CYP21 and CYP21P. These recombinations either delete CYP21 or transfer deleterious mutations from CYP21P to CYP21, a process termed apparent gene conversion. The degree of enzymatic compromise caused by each mutation is correlated with the clinical severity of the deficiency observed in patients carrying that mutation. © 1994 Wiley-Liss, Inc.     

Group C rotavirus associated with fatal enteritis in a family outbreak

A family outbreak of gastroenteritis involving three adults and three children is described in which diarrhoea and vomiting were the main clinical features. One infant died in whom no pathogens could be detected in either small or large intestinal postmortem samples. Stool samples from two symptomatic siblings contained rotaviruses as demonstrated by electron microscopy. Both of these faecal samples were negative when assayed in a group A specific rotavirus enzyme-linked immunosorbent assay (ELISA) and subsequent genomic analysis of these rotaviruses was suggestive of group C rotavirus. Serological evidence showed that these atypical rotaviruses were members of serogroup C. Other atypical rotaviruses in faecal samples from sporadic cases in symptomatic children were detected over a similar time period and location. These had electrophoretic RNA profiles similar to those in the family outbreak. Furthermore, seroepidemiological studies detected group C rotavirus antibody in blood donors resident in the location of the family outbreak.     

TNFalpha expression in hyperplastic endometrium

PROBLEM: Tumor necrosis factor-alpha (TNFalpha) is produced by the endometrium, and it has been shown that this cytokine has cyclic variations through the menstrual cycle. METHOD OF STUDY: In this study we assessed TNFalpha, estradiol and progesterone levels in the endometrium and serum of 21 patients with recent abnormal uterine bleeding (AUB). Eleven women showed histological diagnosis of endometrial hyperplasia, and ten women showed normal endometrium. RESULTS: The TNFalpha value in the serum of patients with hyperplasia and in normal endometrium did not show significant differences (64.8 +/- 21.4 vs 77.6 +/- 14.8 pg). The amounts of TNFalpha released by hyperplastic endometrial tissue were significantly higher than in control patients (258.8 +/- 78.0 vs 140.6 +/- 79.8 pg/g; P < 0.001). Immunohistochemistry of hyperplastic endometria showed a stronger staining than normal ones. Serum E2 levels in patients with hyperplastic endometrium were 49.5 +/- 31.6 ng/mL, and in controls were 107.3 +/- 66.0 ng/mL. The levels of estradiol released by hyperplastic endometria were significantly lower than in normal endometria (152.7 +/- 60.0 vs 279.9 +/- 178.7 ng/g; P < 0.003). CONCLUSIONS: Hyperplastic endometria produce higher amounts of TNFalpha with respect to controls. These findings may explain the frequent bleeding observed in the patients with endometrial hyperplasia, since TNFalpha promotes apoptosis and endometrial shedding.     

Early (Stage A) prostatic cancer

Summary This study was performed in order to elucidate some of the problems of incidence, morphology and natural history concerned with Stage A prostatic cancer or prostatic microcarcinoma (PMC).The prostates of 100 patients, treated by subtotal prostatectomy for benign prostatic hyperplasia (BPH), were studied by comparing both routine and step-section techniques. The incidence of PMC was 41% by the former and 86% by the latter technique. Assessment of the size of PMC, as measured by the sum of the two main diameters, resulted in three groups: A₁, A₂, A₃. The last of these may represent a frankly malignant condition, judged by size and the histological appearance. Radical prostatectomy is strongly suggested as appropriate therapy for this group.Supported in part by a Grant from the Ministry of Education (art. 286 T.U., 1977/78)