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Carcinomas are tumors of epithelial origin accounting for over 80% of all human malignancies. A substantial body of evidence implicates oncogenic signaling by receptor tyrosine kinases (RTKs) in carcinoma development. Here we investigated the expression of Sef, a novel inhibitor of RTK signaling, in normal human epithelial tissues and derived malignancies. Human Sef (hSef) was highly expressed in normal epithelial cells of breast, prostate, thyroid gland and the ovarian surface. By comparison, substantial downregulation of hSef expression was observed in the majority of tumors originating from these epithelia. Among 186 primary carcinomas surveyed by RNA in situ hybridization, hSef expression was undetectable in 116 cases including 72/99 (73%) breast, 11/16 (69%) thyroid, 16/31 (52%) prostate and 17/40 (43%) ovarian carcinomas. Moderate reduction of expression was observed in 17/186, and marked reduction in 40/186 tumors. Only 13/186 cases including 12 low-grade and one intermediate grade tumor retained high hSef expression. The association of hSef downregulation and tumor progression was statistically significant (P

Biological markers are necessary for predicting prognosis of salivary malignancies and better understanding the pathogenesis of salivary cancer. We analysed terminal deoxynucleotidyl transferase (TdT)-mediated biotinylated deoxyuridine-triphosphate (dUTP)-biotin nick-end labelling (TUNEL), p53 and Ki67 expression in 66 patients with malignant salivary tumours by immonohistochemistry, and correlated the data with survival, disease-free survival, tumour grade, stage, and local and distant metastasis. TUNEL efficiently predicted poor prognosis in salivary malignancies. The 5-year (5Y) survival probability dropped significantly with the level of TUNEL staining (from 83% in negatively stained tumours to 57 and 24% in TUNEL positively stained levels 1 and 2, respectively), (P=0.042). Extensive Ki67 staining (in addition to TUNEL) reduced the 5Y-survival rate even further and addition of positively stained p53 dropped the 5Y-survival rate to 0. The correlation rates between TUNEL and Ki67 was 58% (P=0.0001), and between TUNEL and p53 it was 50% (P=0.035). Concurrently, TUNEL correlated with metastasis, extracapsular spread, grade and stage. The correlation between TUNEL, p53 and Ki67 staining and survival probabilities, and the pathological grade, stage and metastasis spread of salivary malignancies makes this a highly effective tool in patient follow-up and prognosis.

In the last year we have encountered three cases of clinically inapparent herpes simplex virus (HSV) tracheitis in biopsies from patients undergoing tracheostomy following prolonged intubation. The diagnosis was based on finding characteristic inclusion-bodies on haematoxylin and eosin stained sections and was confirmed by immunohistochemical staining of infected cells with antibodies to HSV. A prominent mononuclear infiltrate, originally described in HSV oesophagitis, was recognized in two cases. Diffuse squamous metaplasia of both surface and glandular epithelium adjacent to necrotic ulcerated areas was evident in all three cases. Where extensive, the necrotizing squamous metaplasia of the glandular/ductal component was similar to necrotizing sialometaplasia of salivary glands, and likewise simulated squamous or mucoepidermoid carcinoma.

This study was performed to determine whether serial vertical sectioning of scalp biopsies increases the histological diagnostic yield in alopecias.The study group included 100 consecutively referred patients with scalp alopecias. The formalin-fixed paraffin-embedded specimens of the scalp alopecias were completely serially sectioned in a vertical orientation and stained with haematoxylin and eosin. The histological diagnosis rendered in the initial slide harbouring three to six sections was compared with the diagnosis in the following vertical serial sections (30-116 serial sections per specimen, mean 53).A total of 55 scalp biopsies were classified histologically as non-cicatricial alopecia, 35 as cicatricial alopecia and 10 as 'others'. Diagnostic histological findings were present in the initial sections of 50 (50%) cases of alopecia, and only in the following serial sections in 48 (48%) cases. Two cases (2%) lacked differentiating diagnostic histological features in all of the vertical sections. The diagnostic yield of the serial vertical sections compared with the initial sections was higher in the non-cicatricial alopecias (52.7%) than in the cicatricial alopecias (48.5%) and the 'others' category (10%).Serial vertical sectioning of scalp alopecias increases the histological diagnostic yield, substantially.

To find a possible correlation of Ki67 antigen and proliferating cell nuclear antigen (PCNA) with prognosis in anorectal malignant melanoma.Thirty patients with anorectal malignant melanoma were studied. The percentage of tumour cells stained for Ki67 and PCNA in paraffin sections was assessed. Mode of treatment (local excision or abdominoperineal resection), depth of tumour invasion, attempt at cure as defined by complete tumour excision and absence of distant metastases at presentation, tumour blood vessel invasion, and tumour necrosis, as well as Ki67 and PCNA, were all correlated with survival. By univariate analysis, PCNA, Ki67, attempt at cure, local excision (and not abdominoperineal resection), and depth of invasion were all significantly associated with longer survival. By multivariate analysis, only PCNA was significantly associated with survival, while Ki67 showed a significant positive correlation with PCNA. With a cut-off point of 40%, patients with lower Ki67 scores showed survival advantage over those with higher Ki67 scores (P=0.0004). With a cut-off point of 80%, patients with lower PCNA scores showed survival advantage over those with higher PCNA scores (P=0.0001). The staining for proliferation markers was also associated with depth of tumour invasion.Ki67 and PCNA immunostaining in paraffin sections may be useful for the prediction of survival in patients with anorectal malignant melanoma. Larger studies are needed to confirm our results.

Littoral cell angioma is a recently described splenic vascular tumour of splenic sinus lining cells. Almost all cases of splenic littoral cell tumours hitherto described were benign.A splenic littoral cell tumour recurred 8 years after splenectomy, with an abdominal mass and multiple liver metastases, resulting in the patient's death. Histologically, the original splenic tumour showed solid areas with small necrotic foci in addition to large areas of typical littoral cell angioma. The recurrent tumours showed increased solid architecture and slightly increased nuclear atypia. The tumours showed an immunohistochemical profile positive for factor VIII, CD31, CD68, cathepsin D, and CD21 and negative for CD34 and CD8, consistent with the immunophenotype of classic littoral cell angioma. Ki67 index in the recurrent tumours was higher than in the primary tumour.The mildly atypical, but not frankly malignant, histological features as well as the protracted clinical course support definition of the tumour as 'littoral cell haemangioendothelioma'. Low rate of Ki67 staining and diploid DNA histogram with low S-phase fraction of the tumours are in accordance with a low-grade malignancy. Literature review revealed two other cases of littoral cell tumours with disseminated disease that may be other examples of littoral cell haemangioendothelioma. Littoral cell haemangioendothelioma should be distinguished from the overtly malignant splenic angiosarcomas, of which a few may show splenic lining cell differentiation with some immunohistochemical features of littoral cells. Due to difficulties in predicting biological behaviour based on histological features of splenic littoral cell tumours, a long-term follow-up for these patients, especially for those with atypical histology, is recommended.

A 48-year-old man with the nonfamilial form of neurofibromatosis type 1 (NF-1) developed a malignant fibrous histiocytoma in the deep soft tissue of the calf. Following excision and local radiotherapy, the tumor did not recur. At age 59, due to rectal bleeding, a polypoid malignant melanoma of the anal canal was detected and resected. One year later a local recurrence was removed, a pelvic mass was seen on computed tomography, and the patient died. The malignant melanoma was amelanotic and negative for HMB-45 (a melanoma-specific antibody), and the recurrent tumor showed areas of desmoplasia and prominent perineural and intraneural spread. The latter properties underscore the similarities of this melanoma to malignant peripheral nerve sheath tumor. In addition to neurofibroma and malignant schwannoma, NF-1 is associated with other neuroectodermal tumors, including brain tumors and pheochromocytoma. However, it is still controversial whether cutaneous malignant melanoma is more prevalent in NF-1 patients. Anorectal melanoma and malignant fibrous histiocytoma are exceedingly rare in NF-1. Second primary cancers are probably more frequent in NF-1 patients compared to the general population and may be related to alterations in the NF-1 gene.

Fibromatosis (desmoid tumor) can sometimes develop at sites of previous surgery or previous trauma, but it is very rarely detected at sites of prior irradiation. We report two cases of fibromatosis following radiotherapy for Hodgkin's disease. The fibromatoses, developing in the radiation fields, were detected at the posterior area of the neck 11 years after irradiation in one case and in the peritoneal cavity 3 years after laparotomy and irradiation in the second case. The tumors did not differ clinically or histologically from those seen in patients who did not undergo irradiation. Although rare, fibromatosis should enter the differential diagnosis of masses developing in irradiated fields in patients with treated Hodgkin's disease.

We report a benign encapsulated thymoma in an 11-year-old boy. Histologically, it showed foci of medullary differentiation mimicking the normal corticomedullary thymic architecture. We emphasize the rarity of thymomas in children and the possibility of mistaking this uncommon pattern of thymoma for other mediastinal tumors.

A 60-year-old temporary Israeli resident travelled to Arizona, developed an influenzalike infection, and returned with a space-occupying lesion in the lung. Since the patient was a heavy smoker, lung cancer was suspected and he was operated on. A granuloma was reported on frozen sections, and Coccidioides immitis was revealed on stained preparations and by microbiological investigation. Coccidioidomycosis is unusual in Israel; therefore, it is important to be aware of this mycosis in patients who have a history of recent visits to areas of endemicity in North America, Central America, and South America.

A post mortem examination of a 70 year old man, who died three years after a poorly differentiated adenocarcinoma of prostate had been diagnosed, showed widespread signet-ring cell carcinoma, with an associated linitis plastica. The signet-ring cells stained positively with prostatic specific antigen and with prostatic specific acid phosphatase, but failed to react with mucopolysaccharide staining. The electron microscopic appearance of the signet-ring cell tumour was due to the presence of large cytoplasmic vacuoles. This case emphasises the possibility that cases of metastatic signet-ring cell carcinoma may be prostatic in origin. This can be confirmed by specific immunohistochemical studies.

Thirty-three children with idiopathic nephrotic syndrome who underwent kidney needle biopsy were reevaluated. The male to female ratio was 2:1, and a preponderance of North-African Jewish and Arab origin over Ashkenazi Jewish origin was noted. There was a positive correlation between the severity of glomerular changes and prognosis among the 10 cases with minimal change disease (MCD) and the 23 with focal segmental glomerulosclerosis (FSGS). On long-term follow-up (mean over 11 years) chronic renal failure developed in none of 10 MCD patients, 1 of 12 FSGS patients with mild glomerular sclerosis, 1 of 7 FSGS patients with moderate glomerular sclerosis and 3 of 4 FSGS patients with severe glomerular sclerosis. Prognosis of patients with mild glomerular sclerotic lesion on light microscopy was substantially not worse than the prognosis of patients with mild glomerular alterations only on the electron microscopic study (MCD-B). Thus, both pathologically and prognostically, there was a continuous spectrum from 'pure' MCD (MCD-A) to FSGS with severe glomerular sclerosis. Glomerular changes confined to the origin of the proximal tubule ('tip' changes) were seen only in 4 patients and did not have a distinct prognostic significance. No case of peripheral location of the sclerotic segment within the glomerulus was found in our series of FSGS, and therefore no correlation between location of segmental sclerosis and prognosis was feasible.

A case of oat-cell lung carcinoma metastatic to renal oncocytoma is described. The pertinent literature is reviewed.

A patient with hydatid cyst of the liver was found to have a positive direct antiglobulin test, with IgG and complement on his red blood cells (RBCs), but with no evidence of haemolysis. The positive direct antiglobulin test disappeared following surgical removal of the cyst. To the best of our knowledge no such case has been reported in the literature.