[Alertness is its own reward: adult type Hirschprung's disease--clinical description of first two cases in Israel].

Hirschprung disease is well known. The basic pathogenesis is lack of parasympathetic ganglia in the large bowel wall, part of it, or all of it. The absence of these ganglia paralyzes the involved segment leading to obstruction. Almost all babies are diagnosed and operated upon in their first year. Few rare cases manage to grow and reach maturity without diagnosis. These patients are characterized by severe constipation and grade III-IV hemorrhoids. This is adult type Hirschprung's disease. Two first cases in Israel were diagnosed, patients were operated upon, and recovered. Adult type Hirschprung's disease is reviewed and various surgical options are discussed.

[Cutaneous metastases from epithelial ovarian cancer].

Cutaneous involvement is a rare presentation of ovarian cancer. There are only a few such case reports in the literature, most of them in surgical scars or subcutaneous nodules. This is a rare case of a patient presenting with skin metastases originating from primary ovarian carcinoma, which appeared 8 months following a disease-free interval. Based on this case report and a review of the literature, it is concluded that cutaneous involvement in ovarian cancer is a poor prognostic sign. Life expectancy of these patients is only a few months from the time of diagnosis of skin metastases. Thus, one should consider merely a palliative approach in these cases.

Carotid plaque vulnerability: quantification of neovascularization on contrast-enhanced ultrasound with histopathologic correlation.

OBJECTIVE: The purpose of this research is to develop a computerized method to quantify carotid plaque neovascularization on contrast-enhanced ultrasound images and to compare the results with the histopathologic analysis of the plaque. SUBJECTS AND METHODS: Twenty-seven patients (age range, 48-84 years; mean [± SD] age, 68.4 ± 9.72 years) were recruited before endarterectomy. Contrast-enhanced ultrasound examination of the carotid artery was performed by applying low mechanical index and harmonics with pulse inversion. An algorithm was developed that implemented several image processing methods to automatically quantify neovascularization and reconstruct the vascular tree in the atheromatous plaque. Neovascularization and the number of inflammatory cells seen on histopathologic analysis of the plaque after endarterectomy were compared with neovascularization determined by the computerized method. The mean (± SD) ratios of the ultrasound and histopathologic measurements were calculated. RESULTS: In five patients, heavy calcification of the plaque prevented visualization of plaque texture. Intraplaque neovascularization on contrast-enhanced ultrasound images was significant in 19 patients and low in three patients. The ratio of the neovascularization area to the total plaque area on contrast-enhanced ultrasound images was well correlated with the same histopathologic ratio (R(2) = 0.7905) and with the number of inflammatory cells present in the plaque (R(2) = 0.6109). The histopathologic ratio and the number of intraplaque inflammatory cells also were well correlated (R(2) = 0.7034). CONCLUSION: The newly developed method allowed quantification of the intraplaque neovascularization as a feature of vulnerability in the carotid plaque and proved to be highly correlated with histopathologic results.

Successful monozygotic twin pregnancy fathered by a male 46,XY true hermaphrodite.

This report presents an unusual case of absolute non-obstructive azoospermia revealed to be a male 46,XY true hermaphrodite who was successfully treated to father healthy monozygotic twins. A 27-year-old infertile male with non-obstructive azoospermia previously underwent an unsuccessful testicular sperm extraction procedure and refused donor sperm insemination.Revising the patient's old records revealed that he was born with ambiguous genitalia. He had a 46,XY karyotype and was raised as a male. During childhood he underwent ambiguous genitalia reconstruction, right orchiopexy and left salpingo-oophorectomy that revealed a gonadoblastoma. A new treatment was employed performing testicular fine needle aspiration leading successfully to a monozygotic twin pregnancy. As far as is known, this is the first reported case of healthy twins fathered by a male 46,XY true hermaphrodite.

A life-threatening event: uterine cervical arteriovenous malformation.

BACKGROUND: Uterine cervical arteriovenous malformation is a rare cause of vaginal bleeding. CASE: A 32-year-old multigravida presented with severe vaginal bleeding originating in the cervix, which resulted in a hypovolemic shock. Attempts to control the bleeding included hysterectomy, pelvic arterial embolization, and upper vaginectomy. Each proved unsuccessful. Histopathologic examination revealed an arteriovenous malformation. Despite local packing, suturing of the vault area, and brachytherapy to the vaginal vault, bleeding persisted. Treatment with GnRH agonist and tranexamic acid stopped the bleeding. CONCLUSION: Severe vaginal bleeding can be the result of cervical arteriovenous malformation, and GnRH agonist may be used for treatment.

Prognostic role of apoptotic, Bcl-2, c-erbB-2 and p53 tumor markers in salivary gland malignancies.

OBJECTIVE: The clinical characteristics and survival probability rate of 36 patients with salivary gland malignancies and 10 patients with benign salivary tumors were summarized in relation to the immunohistological analysis of the tumor, apoptotic-related markers and apoptosis rate. The expression of the markers examined - Bcl-2, c-erbB-2, p53 - was detected in paraffin sections of the tumors by the streptavidin-biotin peroxidase method following heat-induced antigen retrieval, and the apoptosis rate was determined by the TUNEL method. RESULTS: The overall 5-year survival probability was 61% for patients with malignant tumors and 100% for those with benign tumors. The survival probability of patients over 60 at diagnosis was significantly lower than that of younger patients. Patients whose malignant tumors were larger than 2 cm at diagnosis had worse survival than those with smaller tumors. The survival probability of patients whose malignant tumors were located in the submandibular glands was significantly lower than that of patients whose malignancies were located in the parotid and minor salivary glands. The survival probability of patients who demonstrated positive staining for c-erbB- 2 or TUNEL was lower than for those with negative staining. Gender, the existence of concomitant non-salivary malignancies and ethnic origin had no significant impact on survival. CONCLUSIONS: Our results demonstrated significant positive staining in the salivary tumorigenic tissue but not in the surrounding non-tumorigenic tissue examined for TUNEL, c-erbB-2, Bcl-2 and p53, pointing to a biological role for all four markers in the tumorigenic process which is yet to be elucidated. Significant reduction in survival was related to the specific location of the tumor in the submandibular gland, its size and older age of patient. Survival was also found to be significantly reduced when positive staining was demonstrated in the tumor tissue for TUNEL or c-erbB-2, more so for concomitant positive staining of both markers. Clinically, the most important result of the current study is that the survival rate of the patients examined with salivary tumors larger than 2 cm, with positive staining for both TUNEL and c-erbB-2, was 0 (p = 0.0001)!

Chromium-induced lymph node histiocytic proliferation after hip replacement. A case report.

BACKGROUND: Prosthetic joint replacement is frequently used for the treatment of degenerative joint disease, rheumatoid arthritis, bone tumors and traumatic lesions. The prostheses contain such materials as titanium, cobalt and chromium. We describe a patient who, after total hip arthroplasty, developed an inguinal-pelvic mass. Fine needle aspiration revealed metallic particles, also seen on light microscopy in reactive pelvic lymph nodes. Ultrastructure was consistent with the presence of foreign particles, while energy dispersive x-ray microanalysis established the presence of chromium. To our knowledge, this is the first report of chromium-related lymph node metallosis diagnosed by fine needle aspiration. CASE: Eight years after total hip arthroplasty, a 78-year-old woman developed a right pelvic cystic mass. Aspiration drainage was performed. Smears from fine needle aspiration showed numerous macrophages with abundant, foamy cytoplasm and round nuclei without atypia. Small, birefringent particles were seen in the cytoplasm. Histopathology showed fibroconnective tissue with chronic inflammation and marked lymph node sinus histiocytosis. Within histiocytes, numerous particles were present, identical to those seen in the smears. Their nature as "foreign bodies" was confirmed by electron microscopy, and the presence of chromium was shown by energy dispersive x-ray analysis. CONCLUSION: Fine needle aspiration and polarized microscopy are excellent techniques to evaluate foreign materials in lymph nodes draining the sites of joint prostheses, thus precluding confusion with other conditions, such as metastatic carcinoma.

The use of a single serological marker underestimates the prevalence of celiac disease in Israel: a study of blood donors.

OBJECTIVES: Recent studies suggest that celiac disease was previously underdiagnosed. To find out whether antiendomysial antibodies underestimate the prevalence of celiac disease, we elected to use a strategy combining multiple serological markers to explore the prevalence of celiac disease in Israel and the usefulness of the various antibodies in screening for celiac disease. METHODS: Serum samples from 1571 healthy blood donors were tested. A small intestinal biopsy was offered to all patients who tested positive for either human tissue transglutaminase antibodies, an ELISA kit based on antiendomysium (EMA-ELISA), immunoglobulin A antigliadin verified by antiendomysial immunofluorescence antibodies, and to patients who were IgA deficient with elevated antigliadin IgG. RESULTS: A total of 59 subjects (3.8% of study population) were offered an intestinal biopsy based on serological findings, and 30 of 59 patients agreed to undergo intestinal biopsy (1.9% of study population). Celiac disease was diagnosed in 10 patients, establishing a prevalence of at least 1:157 in the general population (0.6%, CI = 0.3-1.1%). Using any serological marker alone would have underestimated the prevalence of celiac disease, as it was diagnosed in only two patients who tested positive for endomysial immunofluorescence antibodies (prevalence of 1:786, 0.1%, CI = 0.02-0.5%), six patients positive for tissue transglutaminase (prevalence of 1:262, 0.4%, CI = 0.1-0.9%), and seven patients positive for ELISA-EMA (prevalence of 1:224, 0.45%, CI = 0.2-0.9%). CONCLUSIONS: The prevalence of celiac disease in Israel is at least 1:157 in the general population, confirming its underdiagnosis in previous studies. The disparity between the various serological markers suggest that the use of one serological marker is insufficient for establishing the true prevalence of celiac disease.

Squamous cell carcinoma of the tongue: the prevalence and prognostic roles of p53, Bcl-2, c-erbB-2 and apoptotic rate as related to clinical and pathological characteristics in a retrospective study.

In the current study, we examined the clinical characteristics and survival probability rates of 116 patients treated for squamous cell carcinoma (SCC) of the tongue. In 55 randomly selected patients these data were correlated with the immunohistological analysis of the tumor and apoptosis-related markers, p53, Bcl-2, c-erbB-2 (Her-2/neu), and to the apoptosis rate assessment by the terminal dUTP nick-end-labeling (TUNEL) method. The overall 5-year survival probability was 55%, which might be the result of the low incidence of smoking and/or alcohol consumption among the patients (21%), the early diagnosis (65% at Stages I-II) and the low histological grades (91% good-moderate). Radiotherapeutic or surgical treatment of the neck did not alter the survival probability achieved by local surgery for Stage I patients, but significantly improved survival for Stage II patients. Independent tumor-related variables which significantly worsened the probability of survival were found. Concomitant non-oral cancer was found to be a poor variable for prognosis prediction. Positive staining of p53, TUNEL (apoptosis rate), c-erbB-2 and Bcl-2 was found in 60, 48, 18 and 15% of the lesions, respectively (P<0.0001). The possible biological significance of these markers in tongue SCC is discussed in relation to the current literature, and an independent role for TUNEL and p53 is suggested.

Cancer-testis antigen expression in uterine malignancies with an emphasis on carcinosarcomas and papillary serous carcinomas.

The cancer testis (CT) family of antigens are expressed in certain malignant neoplasms and are silent in normal adult tissues, except for the testis. Expression of 2 members of this family, MAGE-A4 and NY-ESO-1, has been described recently in germ cell tumors, malignant melanomas, certain carcinomas and sarcomas. Our study is the first to describe the expression pattern of CT antigens in uterine neoplasms. Ninety-eight cases of uterine neoplasms, including 41 endometrioid, 19 papillary serous and 7 clear cell carcinomas, 22 carcinosarcomas and 9 endometrial stromal sarcomas were studied. Immunohistochemistry was carried out with the 57B monoclonal antibody that recognizes predominantly the MAGE-A4 antigen in paraffinized tissues and the D8.38 antibody that recognizes NY-ESO-1. MAGE-A4 expression was found to be present in 12% of the endometrioid adenocarcinomas, 63% of the papillary serous carcinomas and 91% of the carcinosarcomas. Within the tumor population the extent of MAGE-A4 expression was highest in the carcinosarcomas. In 12 of 22 positively staining carcinosarcomas more than 50% of the tumor cells expressed MAGE-A4. NY-ESO-1 expression was seen in 19% of the endometrioid adenocarcinomas, 32% of the papillary serous carcinomas and in 45% of the carcinosarcomas. CT antigen immunoreactivity was observed in both the carcinomatous and sarcomatous components of the carcinosarcomas and strong correlation between MAGE-A4 and NY-ESO-1 expression was present in individual cases. In summary, strong MAGE-A4 expression and to a lesser degree NY-ESO-1 expression is characteristic of the vast majority of uterine carcinosarcomas and a major subset of papillary serous carcinomas. These results suggest that CT antigen expression by these tumors may represent a novel target for immunotherapy.

Psoriasis is mediated by a cutaneous defect triggered by activated immunocytes: induction of psoriasis by cells with natural killer receptors.

This study was performed to ask whether psoriasis is a unique pathologic response of epidermis of psoriatic patients, or cells with natural killer receptors can induce psoriatic changes in skin from nonpsoriatic donors. Human nonlesional skin from five psoriatics, as well as from seven nonpsoriatics was grafted on to beige-SCID mice. Lymphocyte lines with natural killer activity, and mixed natural killer, natural killer T cell phenotype, were generated by culture of peripheral blood mononuclear cells from both psoriatic, and normal donors, in 100 U interleukin-2 per ml for 14 d. Natural killer cells were injected into the human skin grafts, and the grafts were harvested after 4 wk. Injection of natural killer cells from psoriatic donors into autologous nonlesional psoriatic skin resulted in classic psoriasis histology with a significant increase in epidermal thickness, and proliferation, as well as expression of epidermal human leukocyte antigen DR, intercellular adhesion molecule-1, CD1d, and K-16. Superantigen stimulation was not necessary. In contrast, injection of natural killer cells from normal donors into autologous normal skin did not induce the histology of psoriasis, but that of psoriasiform dermatitis. This is a nonspecific reaction pattern. These grafts also exhibited a significant increase in epidermal thickness, and proliferation. Differences from psoriasis included mild epidermal edema (spongiosis), hypergranulosis, irregular elongation of rete ridges, and lack of thinning of the suprapapillary plate. Injection of allogeneic natural killer cells into grafts also resulted in psoriasiform dermatitis, regardless of the source of natural killer cells, or skin. Psoriasis induction by cells with natural killer receptors appears to be dependent upon the source of skin. This suggests that psoriasis results from a cutaneous defect that is triggered by an autoimmune activation.

Human telomerase RNA component expression in Spitz nevi, common melanocytic nevi, and malignant melanomas.

BACKGROUND: Telomerase is a ribonucleoprotein DNA polymerase that is capable of synthesizing telomeres onto the ends of chromosomes. The cumulative loss of telomerase activity is believed to be associated with cell senescence. Telomerase activity has been shown to be higher in malignant melanomas than in common melanocytic nevi. The aim of the present study was to elucidate the pattern of expression of the human telomerase RNA (hTER) component in routinely processed specimens of Spitz nevi, malignant melanomas, and ordinary melanocytic nevi. METHODS: Ten specimens of each type of tumor were studied, using an in situ hybridization technique. RESULTS: All three types of tumors demonstrated moderate to high intensities of hTER expression, usually in more than half of the tumor cells, and the majority of the studied lesions in each group did not show stratification of staining. The hTER component was also detected in the epidermis, sweat glands, and pilosebaceous units. CONCLUSIONS: hTER levels do not necessarily correlate with the level of telomerase activity, and the level and pattern of hTER expression are not useful as an adjunct to the histologic differential diagnosis of Spitz nevi from melanocytic nevi and malignant melanomas.

Obstructing gastric heterotopic pancreas: case report and literature review.

Heterotopic pancreas (HP) is generally an asymptomatic lesion and is a rare cause of gastric outlet obstruction. We report such a case in which both upper gastrointestinal series and abdominal computerized tomography (CT) demonstrated an antral mass; surgical and histological results are also reported.