Cytodiagnosis of simple and proliferating trichilemmal cysts

OBJECTIVE: To elucidate the cytologic findings in simple trichilemmal (pilar) cysts and proliferating trichilemmal cysts (pilar tumors) and the clinical importance of these lesions. STUDY DESIGN: Aspirates from 12 simple pilar cysts and three pilar tumors, all histologically confirmed, were analyzed with a view to elaborating on specific cytologic features enabling a distinction from epidermal cysts and other adnexal tumors. RESULTS: Aspirates from pilar cysts showed two different pictures, depending on the age of the cyst. Young pilar cysts showed aspirates with an abundant background of blotchy keratin with or without calcification and inflammation. Older (degenerating) cysts showed oily fluid debris with cholesterol crystals and inflammatory cells. The epithelial component was sparse, and only an occasional syncitial cluster of small squamoid cells was seen. As opposed to this, epidermal cysts usually showed a cleaner background, with very cellular aspirates containing many nucleate and anucleate squames, keratin flakes, platelike crystals and no calcification. The pilar tumors showed a lesser amount of keratin as compared to pilar cysts and yielded large and small clusters of squamoid and basaloid cells, a few of which showed an abrupt association with anucleate, keratinized globules. CONCLUSION: The cytologic diagnosis of a pilar cyst should be made especially in scalp cysts, which yield either abundant, blotchy keratin or oily, cholesterol-rich debris with a sparse epithelial component and which lack a mixture of anucleate and nucleate squames. On aspiration, pilar tumors yield comparatively more cells and less keratin and show small, basaloid or squamoid cells abruptly associated with keratin globules. The cytologic diagnosis of pilar cysts is important because these cysts recur if incompletely excised and often undergo transformation to pilar tumors. Similarly, pilar tumors often clinically mimic squamous carcinomas, and hence there is a need to outline definitive cytologic features.     

Cytologic and histologic findings in multiple renal hybrid oncocytic tumors in a patient with Birt-Hogg-Dubé syndrome: a case report

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant neoplastic syndrome characterized by multiple skin lesions, lung cysts and renal tumors. A variety of histologic types of renal tumors have been reported, including clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, oncocytoma and a recently described hybrid oncocytic tumor, which is thought to be highly associated with BHD. CASE: We report a case of a 48-year-old woman with BHD who initially presented to our institution with spontaneous pneumothorax and was found to have multiple lung cysts and renal tumors on computed tomography. We describe the fine needle aspiration findings of one of the renal tumors, which was suggestive of so-called hybrid oncocytic tumor. We also describe the gross and histologic findings of the multiple kidney tumors that the patient subsequently had excised. CONCLUSION: When multiple kidney tumors from a single patient appear oncycytic on fine needle aspiration, especially when focal clear cells are present, the possibility of oncocytomas and hybrid tumors associated with BHD must be entertained.     

Immunohistochemical profile of ovarian inclusion cysts in patients with and without ovarian carcinoma

Summary The expression of cytokeratin, epithelial membrane antigen, Leu-M1, B72.3, carcinoembryonic antigen, human placental lactogen, proliferating cell nuclear antigen, p53, and ovarian carcinoma-associated antigen OC-125 was evaluated in inclusion cysts in contralateral ovaries of patients with unilateral ovarian carcinoma. The findings were compared with the findings in inclusion cysts in ovaries of patients without ovarian carcinoma. Although there was more frequent expression of tumour markers B72.3 and CEA in patients with ovarian carcinoma, these differences did not reach statistical significance.     

Giant Cysts and Cysts with Multiple Central Bodies in Azotobacter vinelandii

Cyst germination in Azotobacter vinelandii ATCC 12837 was studied by using phase contrast and electron microscopy. Germination in this organism was accompanied by the formation of large cyst forms of two different types: giant cysts and cysts containing multiple central bodies. Previously, these two types have been reported only when yeast extract was added to the encystment medium. In this study, we observed giant cysts and cysts with multiple central bodies in nitrogen-free liquid medium. The germination of "normal" cysts is often preceded by enlargement to the giant form and division of the central body to produce cysts with multiple central bodies. Structures similar in appearance to ribosomal aggregates were observed only in cysts undergoing pregermination transformations.     

Equine granulosa-theca cell tumors express inhibin alpha- and beta A-subunit messenger ribonucleic acids and proteins

The association of equine granulosa-theca cell tumors with atrophied contralateral ovaries and abnormal estrous cycles suggests that these tumors produce hormones that affect pituitary gonadotropin production. Because inhibin, a heterodimer protein secreted by granulosa cells, decreases FSH production, we examined the presence of inhibin alpha- and beta A-subunits and their mRNAs in ovarian tumors obtained from three mares. These tumors contained neoplastic cords and nodules, multiple fluid-filled cysts, and a predominance of neoplastic granulosa cells. Reduced proteins from tumor-conditioned media were analyzed by electrophoresis and immunoblotting using antibodies directed against peptide fragments of the alpha- and beta A-chains of porcine inhibin. Specific bands at 50-kDa and 36-kDa for the inhibin alpha-subunit and at 44 kDa and 13 kDa for the inhibin beta A-subunit were observed in these tumors. Northern blot hybridization of 32P-labeled rat inhibin alpha- and beta A-subunit complementary RNAs to total RNA from each tumor revealed predominant bands of activity in all three tumors at 1.5 and 7 kb for the alpha- and beta A-subunit mRNAs, respectively. These results demonstrate that equine granulosa-theca cell tumors express the mRNAs for inhibin alpha- and beta A-subunits and also secrete inhibin subunits that could potentially affect gonadotropin production in afflicted mares. Furthermore, cells derived from these tumors may provide a useful model for understanding inhibin gene regulation and ovarian tumorigenesis.     

Expression of the differentiation antigen of activated T and B lymphocytes (ACA-1) on cells of lymphoid and nonlymphoid tumors

In cytotoxicity and indirect immunofluorescence tests an antiserum to ACA-1 (activated cell antigen) reacted with 58–100% of actively proliferating cells from tumors of lymphoid (EL-4 T lymphoma, MOPC 104E plasmacytoma) and nonlymphoid origin (AH-22 hepatoma, Sa-1 and MCh-11 sarcomas, F2 mammary cancer). Absorption of anti-ACA-1 serum with tumor cells sharply reduced its activity both against the cells of all these neoplasms and against normal activated T and B lymphocytes. Absorption with proliferating murine cells from the brain of embryos and the retina of neonates or with similar (nonproliferating) cells from adult mice did not affect the activity of the antiserum. It is concluded that ACA-1 is expressed on actively proliferating cells of the tumors studied.     

High expression of antizyme inhibitor 2, an activator of ornithine decarboxylase in steroidogenic cells of human gonads

High activity of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis, is typically present in rapidly proliferating normal and malignant cells. The mitotically inactive steroidogenic cells in rodent testis and ovaries, however, also display high ODC activity. The activity of ODC in these cells responds to luteinizing hormone, and inhibition of ODC reduces the production of steroid hormones. Polyamines and ODC also control proliferation of germ cells and spermiogenesis. The activity of ODC, especially in proliferating cells, is regulated by antizyme inhibitor (AZIN). This protein displaces ODC from a complex with its inhibitor, antizyme. We have previously identified and cloned a second AZIN, i.e. antizyme inhibitor 2 (AZIN2), which has the highest levels of expression in brain and in testis. In the present study, we have used immunohistochemistry and in situ hybridization to localize the expression of AZIN2 in human gonads. We found a robust expression of AZIN2 in steroidogenic cells: testicular Leydig cells and Leydig cell tumors, in ovarian luteinized cells lining corpus luteum cysts, and in hilus cells. The results suggest that AZIN2 is not primarily involved in regulating the proliferation of the germinal epithelium, indicating a different role for AZIN1 and AZIN2 in the regulation of ODC. The localization of AZIN2 implies possible involvement in the gonadal synthesis and/or release of steroid hormones.     

Multiple unusual locations of hydatid cysts including bladder, psoas muscle and liver

Our case concerns 66-year-old female with a multiple unusual locations of hydatid cysts including bladder, psoas muscle and liver. Coexistence of hydatid cysts in these localizations has not been previously reported. The diagnosis of vesical hydatid cyst was facilitated by the coexistence of other echinococcosis locations. Treatment consists of the excision of the cysts in the same session without any postoperative anthelmintic drugs. In a two-year follow-up no recurrence has occurred.     

Changes in the cellular phenotype and extracellular matrix during progression of estrogen-induced mesenchymal kidney tumors in Syrian hamsters.

The cellular origin of estrogen-induced kidney tumors in male Syrian hamsters has been repeatedly the subject of controversy. Several authors have proposed that the tumors arise from proximal tubules, from a combination of tubular and interstitial stromal cells, or solely from interstitial cells. Because of the model character of this tumor for hormone-associated cancer, it was further investigated in this study with respect to morphology, enzyme and intermediate filament pattern, the expression of alpha-smooth muscle actin and the extracellular matrix proteins fibronectin and tenascin. These analyses were carried out with early and late tumors as well as metastases to determine possible changes in expression of biochemical parameters during the development and progression of this neoplasm. The enzyme histochemical and intermediate filament patterns were usually the same as those described previously for proliferative foci and early tumors, i.e. highly elevated activities of glucose-6-phosphate dehydrogenase, adenylate cyclase and alkaline phosphatase, a lack of glucose-6-phosphatase and gamma-glutamyltransferase and coexpression of vimentin and desmin, alpha-smooth muscle actin could not be detected in early lesions. In five of 24 advanced tumors inclusions of kidney tubules were found which showed various degrees of alteration in their morphology and enzyme histochemical pattern, but were often directly connected with tubular segments of normal appearance outside the tumor. Like the normal tubules, the enclosed tubular segments were strongly positive for cytokeratin but never expressed vimentin or desmin. Among the 24 tumors studied, two contained cysts which expressed cytokeratin and sometimes also vimentin but not desmin. The enzyme histochemistry of the cells lining the cysts was similar to that of the surrounding tumor mass, except adenylate cyclase was lacking and alkaline phosphatase was not uniformly distributed. In tumors containing cytokeratin-positive cysts, there often were cytokeratin-positive, vimentin-negative and desmin-negative tumor formations in close contact to these cysts. With the exception of cyst formation, the pattern of metastases were identical to that of the primary tumors. All large tumors and the main component of the metastases expressed vimentin, desmin and fibronectin. Mesothelia surrounding metastatic tumor complexes were positive for vimentin, desmin, alpha-smooth muscle actin, fibronectin, cytokeratin and tenascin. It was concluded from these and previous observations on early stages of tumor development that the estrogen-induced hamster kidney tumor originates from mesenchymal interstitial cells (probably pericytes) which may rarely acquire an epithelial phenotype by metaplastic transformation during tumor progression.     

Telomerase activation in mouse mammary tumors: lack of detectable telomere shortening and evidence for regulation of telomerase RNA with cell proliferation.

Activation of telomerase in human cancers is thought to be necessary to overcome the progressive loss of telomeric DNA that accompanies proliferation of normal somatic cells. According to this model, telomerase provides a growth advantage to cells in which extensive terminal sequence loss threatens viability. To test these ideas, we have examined telomere dynamics and telomerase activation during mammary tumorigenesis in mice carrying a mouse mammary tumor virus long terminal repeat-driven Wnt-1 transgene. We also analyzed Wnt-1-induced mammary tumors in mice lacking p53 function. Normal mammary glands, hyperplastic mammary glands, and mammary carcinomas all had the long telomeres (20 to 50 kb) typical of Mus musculus and did not show telomere shortening during tumor development. Nevertheless, telomerase activity and the RNA component of the enzyme were consistently upregulated in Wnt-1-induced mammary tumors compared with normal and hyperplastic tissues. The upregulation of telomerase activity and RNA also occurred during tumorigenesis in p53-deficient mice. The expression of telomerase RNA correlated strongly with histone H4 mRNA in all normal tissues and tumors, indicating that the RNA component of telomerase is regulated with cell proliferation. Telomerase activity in the tumors was elevated to a greater extent than telomerase RNA, implying that the enzymatic activity of telomerase is regulated at additional levels. Our data suggest that the mechanism of telomerase activation in mouse mammary tumors is not linked to global loss of telomere function but involves multiple regulatory events including upregulation of telomerase RNA in proliferating cells.     

Changes in the cellular phenotype and extracellular matrix during progression of estrogen-induced mesenchymal kidney tumors in Syrian hamsters

The cellular origin of estrogen-induced kidney tumors in male Syrian hamsters has been repeatedly the subject of controversy. Several authors have proposed that the tumors arise from proximal tubules, from a combination of tubular and interstitial stromal cells, or solely from interstitial cells. Because of the model character of this tumor for hormone-associated cancer, it was further investigated in this study with respect to morphology, enzyme and intermediate filament pattern, the expression of α-smooth muscle actin and the extracellular matrix proteins fibronectin and tenascin. These analyses were carried out with early and late tumors as well as metastases to determine possible changes in expression of biochemical parameters during the development and progression of this neoplasm. The enzyme histochemical and intermediate filament patterns were usually the same as those described previously for proliferative foci and early tumors, i.e. highly elevated activities of glucose-6-phosphate dehydrogenase, adenylate cyclase and alkaline phosphatase, a lack of glucose-6-phosphatase and γ-glutamyltransferase and coexpression of vimentin and desmin. α-smooth muscle actin could not be detected in early lesions. In five of 24 advanced tumors inclusions of kidney tubules were found which showed various degrees of alteration in their morphology and enzyme histochemical pattern, but were often directly connected with tubular segments of normal appearance outside the tumor. Like the normal tubules, the enclosed tubular segments were strongly positive for cytokeratin but never expressed vimentin or desmin. Among the 24 tumors studied, two contained cysts which expressed cytokeratin and sometimes also vimentin but not desmin. The enzyme histochemistry of the cells lining the cysts was similar to that of the surrounding tumor mass, except adenylate cyclase was lacking and alkaline phosphatase was not uniformly distributed. In tumors containing cytokeratin-positive cysts, there often were cytokeratin-positive, vimentin-negative and desmin-negative tumor formations in close contact to these cysts. With the exception of cyst formation, the pattern of metastases were identical to that of the primary tumors. All large tumors and the main component of the metastases expressed vimentin, desmin and fibronectin. Mesothelia surrounding metastatic tumor complexes were positive for vimentin, desmin, α-smooth muscle actin, fibronectin, cytokeratin and tenascin. It was concluded from these and previous observations on early stages of tumor development that the estrogen-induced hamster kidney tumor originates from mesenchymal interstitial cells (probably pericytes) which may rarely acquire an epithelial phenotype by metaplastic transformation during tumor progression.     

Multilocular cystic renal cell carcinoma with focus on clinical and pathobiological aspects

Multilocular cystic renal cell carcinoma (MCRCC) accounts for approximately 1 to 2% of all renal tumors. This tumor is currently classified as a subtype of clear cell RCC. Clinically, the majority of these tumors are incidentally found. Macroscopically, the tumor is well demarcated and consists of various-sized cysts. The fibrous septa are generally thin and there is no discernible expansile nodule. Microscopically, the cyst walls are lined with tumor cells with clear to occasionally slightly eosinophilic cytoplasm. The Fuhrman nuclear grade is generally low and usually corresponds to grade 1. The deletion of chromosome 3p was identified in most tumors using FISH analysis and VHL gene mutation was identified in 25% of MCRCC. As MCRCC generally exhibits a low stage of TNM classification, the great majority of these tumors have a favorable clinical course. To date, there are no reports of metastasis, vascular invasion or sarcomatoid change in MCRCC. Accordingly, nephron sparing surgery is first recommended as a therapeutic strategy.     

Morphology of the cyst of Giardia microti by light and electron microscopy

Cysts of Giardia microti, isolated from feces and intestinal contents of Microtus ochrogaster, were examined by light and electron microscopy. These cysts differed morphologically from cysts of other G. duodenalis morphological types in that these cysts often contained two apparently differentiated trophozoites with mature ventral discs. Cysts more closely resembling those reported for G. lamblia and G. muris were in greater abundance in preparations made from intestinal contents and were interpreted as immature cysts. "Multiple fission" cysts, reported in G. muris and G. microti by earlier workers, were not observed; however, endosymbiotic bacteria were found in the cysts of G. microti and may have been responsible for reports of multiple fission in the cysts of Giardia.     

Changes in cytoskeleton-associated molecules in cells with different degrees of proliferation and metastatic ability

An antiserum prepared against the Triton-insoluble cytoskeleton of in vivo grown B16 melanoma tumor has been used to analyze the differential expression of cytoskeleton-associated molecules in cells with different degrees of proliferation and metastatic ability. This antiserum identified a major 97 kd molecule associated with the cytoskeletal fraction in B16 melanoma tumors, mouse embryo and in proliferating lymphocytes, with no reactivity with the 97 kd species in non proliferating lymphocytes. The antiserum revealed immune reactivity with a 180 kd Triton-insoluble species in normal adult mouse liver and kidney. A comparison of tumor cells with differing metastatic ability also showed a minor 180 kd component in poorly metastatic cells which appeared decreased and partly degraded in its more invasive counterpart. The differential recognition of a 97 kd species in resting and proliferating lymphocytes, as well as the different cleavage of a 180 kd species in tumor cells of differing metastatic ability, implies a role for these molecules in cell proliferation. The fact that these differences can be detected with an antiserum to tumor cell cytoskeleton suggests that this Triton-insoluble fraction may be a good source of molecules involved in growth control.     

Ovarian carcinoma of low malignant potential treated at the 1(st) Department of Obstetrics and Gynecology Semmelweis University Faculty of Medicine,between 1990 and 2000

The authors analyzed the epidemiologic and histological characteristics and the management of ovarian carcinoma of low malignant potential (LMP) at a university hospital between 1990 and 2000. The authors carried out a retrospective study reviewing hospital charts. Based on the records experience with 29 such tumors is peresented. Of these 20 (74%) were of the serous variety, 7 (26%) were mucinous. LMP tumors accounted for 16% of proliferating epithelial ovarian tumors. They occured at a mean age of 45 years. The LMP tumors were bilateral in 12% of the cases. The majority of patients (87%) with LMP tumors presented with early stage disease. Tumor markers such as CA-125 were not always elevated as in invasive ovarian carcinoma. Laboratory investigations have not demonstrated that these tumors represent an intermediate step between benign ovarian tumors and carcinoma. The recommended therapy is surgical, consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and tumor debulking. Conservative surgery consisting of unilateral salpingo-oophorectomy is considered to be an appropriate treatment for young women with early stage LMP ovarian tumors who wish to retain their fertility potential. 50 percent of women who underwent conservative surgery subsequently conceived in this study. There were no recurrences in the study group, so the authors conclude that the long term outcome of LMP tumors is extremely favorable.     

Comparison of biochemical markers between benign and malignant ovarian cysts

To investigate the presumption that earlier diagnosis of ovarian tumors might lead to an improved outcome, we compared several substances in the fluid of benign and malignant ovarian cysts. Our results showed the following: (1) benign cysts were readily separated from malignant cysts on the basis of total lactate dehydrogenase (LD) activity and except for mucinous cysts, by their isoenzyme patterns. (2) Preoperative serum total LD activity and LD isoenzymes were of no diagnostic help in predicting the malignant tumors. (3) Carcinoembryonic antigen (CEA) levels usually differed greatly between benign and malignant cysts, although the benign mucinous cysts had CEA levels indistinguishable from malignant cysts. (4) Prominent quantitative differences between Roche and Abbott CEA activity were present in both benign and malignant cysts. (5) Preoperative serum CEA levels were not helpful in differentiating the benign from the malignant cysts.     

AgNOR count in resting cells (resting NOR) is a new prognostic marker in invasive bladder tumor.

PURPOSE: We have previously demonstrated that the AgNOR count in proliferating cells is a predictor of tumor recurrence in superficial bladder tumor (J. Urol. 162 (1999), 63-68). In the present study, we evaluate the type of AgNOR associated with cell cycles as a prognostic factor in invasive bladder tumor using a double staining technique employing both AgNOR and MIB-1 labelling. MATERIALS AND METHODS: Forty-four paraffin sections of invasive bladder tumors were stained simultaneously with AgNOR and MIB-1. The number of AgNORs in proliferating (MIB-1 positive) or resting (MIB-1 negative) cells were counted from a total of 100 nuclei. Correlations between MIB-1 associated AgNOR count and clinicopathological parameters were statistically analyzed. RESULTS: The AgNOR count in proliferating cells (proliferating NOR) was significantly higher than that in resting cells (resting NOR) (p<0.01). The resting NOR in tumors with distant metastases was significantly higher than that in tumors without metastases (p<0.05). Patients with a low resting NOR tumor had a better prognosis than those with a high resting NOR tumor, whereas the proliferating NOR was not associated with survival. Survival analysis revealed that the resting NOR was the most powerful prognostic marker in patients with invasive bladder tumor (p<0.05). CONCLUSIONS: Resting NOR had a predictive value in the prognosis of patients with invasive bladder tumor.     

Analysis of DNA-ploidy using laser scanning cytometer in brain tumors and its clinical application

There have been few reports on investigation of the cell kinetics of brain tumors using a laser scanning cytometer (LSC). We compared DNA analysis using a flow cytometer (FCM) with that by LSC using established cell lines of brain tumors, and we demonstrated the similarity of both analytical results. The DNA-index (DI) and proliferating index (PI) of various brain tumors were determined, and the results showed that these indices reflected the malignancy of the tumors. The DI values were higher for astrocytoma grade IV than for astrocytoma grade II, frequently showing an aneuploid pattern. The determination of DNA-ploidy using LSC, together with cryopathological diagnosis, was considered to be useful for deciding the area to be resected for glioma perioperatively and to be worth applying clinically.