Post-irradiation vaginal spindle cell sarcoma.

The genetic profile is one of the major possible causes of spindle cell sarcoma. Irradiation has also been linked to this type of cancer. This means that if tissues have already been irradiated for other types of cancer, they can afterwards develop this form of sarcoma. Also, previous radiotherapy can determine specific genetic alterations, which result to uncontrolled cell division, that is neoplasia. We report one such cause in a female patient 80 years old with a uterus adenocarcinoma (endometrioid type) FIGO Stage IC, who had been treated with surgical resection and pelvic irradiation. Ten years after radiotherapy a vaginal spindle cell sarcoma was diagnosed by cytology (Pap smear) and confirmed by histology and immunohistology. This case is presented to focus the ability of cytology in diagnosis of spindle cell sarcoma in Pap smear with confirmation by histo-immunohistology.

Cytopathology in the diagnostic appraisal of uncommon malignant neoplastic lesions.

Cytology and fine needle aspiration (FNA) cytology are accepted means of diagnosing and typing of common forms of malignant tumors. However, their usefulness for diagnosing less common neoplasms is not clearly established and this study was designed to examine this. We report four unusual cases of patients with malignant neoplasms in which cytology and fine needle aspiration cytology or aspiration biopsy (FNAC, FNAB) contributed significantly in establishing the diagnosis. These cases facilitate the diagnostic capabilities of cytology over a wide spectrum of neoplasms including rare lymphoproliferative disorders and carcinomas.

Carcinoma urotelial plasmocitoide de la vejiga con extensión peritoneal. Diagnóstico citológico en líquido ascítico / Plasmacytoid urothelial carcinoma of the bladder with peritoneal spread. Cytological diagnosis in ascitic fluid

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Primary effusion lymphoma with aberrant T-cell phenotype in an iatrogenically immunosuppressed renal transplant male: cytologic diagnosis in peritoneal fluid.

Primary effusion lymphoma (PEL) is an unusual class of non-Hodgkin's lymphoma that develops in body cavities, without associated mass lesions. It has been linked to human herpes virus 8 (HHV-8), an etiological factor of Kaposi's sarcoma. Although PEL is a B-cell lymphoma, the neoplastic cells are usually of the "null" phenotype by immunocytochemistry. The relative infrequency of this entity, the absence of wide casuistic allowing a better characterization, and its unfavorable outcome, strongly support the need of a deeper knowledge. We report the clinico-biological findings of a 49-year-old male who was iatrogenically suppressed patient for 29 years because of renal transplantation. This case was diagnosed cytologically as peritoneal PEL and confirmed histologically on peritoneal biopsies. The immune status for both HHV-8 and Epstein-Barr virus (EBV) was evaluated and showed positive immunostaining only for the former. The combination of the immunocytochemistry results with the existence of a clonal rearrangement in the immunoglobulin heavy chain gene (identified by PCR) was compatible with the diagnosis of PEL. The presence of T-cell markers was consistent with the diagnosis of PEL with an aberrant T-cell phenotype.

Myoepithelial carcinoma of the parotid gland.

Myoepithelial carcinomas exhibit a wide spectrum of cytomorphologic features and diverse clinical outcomes. As a result of their morphologic heterogeneity, they can be confused easily with many tumours. Herein we report the morphological features of myoepithelial carcinoma in a 74-year-old female clinically presenting with a parotid mass. FNAB revealed hypercellular, three-dimensional clusters with considerable overlapping and crowding of pleomorphic neoplastic cells which consisted predominantly of spindle cells, with oval to elongated to spindle shaped nuclei showing considerable variation in size. The excised tumour was solid, with cells arranged in trabeculae, nests and cords. Tumour cells were mixed epithelioid and spindle with eosinophilic or clear cytoplasm, with eccentric nuclei and prominent nuclei. Neoplastic cells were found in blood vessels, in the skin and facial nerve. Tumour cells were immunopositive for PAS, PAS-D, S-100 protein, GFAP, P63, CK5/ CK6, CK7, and CK14. This case illustrates that cytological features in FNAB generally reflect the histology. FNAB was able to confirm the diagnosis and guide patient management.

ERCC1 expression correlated with EGFR and clinicopathological variables in patients with non-small cell lung cancer. An immunocytochemical study on fine-needle aspiration biopsies samples.

PURPOSE: Expression of ERCC1 has not been well described in fine-needle aspiration biopsies (FNABs) in patients with non-small cell lung cancer (NSCLC). We investigated the expression of ERCC1 in correlation with EGFR expression and clinicopathological factors in patients with NSCLC in order to determine if these play a role in the prognosis of the disease. METHODS: We studied 45 patients, 34 with adenocarcinoma and 11 with squamous cell carcinoma. Of these 45 patients, 35 were males and 10 females, aged between 45 and 83 years, 30 smokers and 15 non-smokers. Eighteen (18) tumors were of stage I, twelve (12) stage II and fifteen (15) stage III. To investigate the expression of ERCC1 and EGFR (scores 0, 1, 2, 3), immunocytochemistry was performed on air dried specimens (FNABs) using monoclonal antibodies by alkaline-phosphatase (APAAP) method. RESULTS: ERCC1 expression was detected in tumors from 27 patients (60%) and EGFR in 10 patients (22.2%). ERCC1 was expressed more frequently in males (65.7%) in patients >65 years old (64%), in smokers (66.7%) and in stage I (66.7%). Negative ERCC1 expression was significantly associated with the presence of EGFR. EGFR was expressed only in adenocarcinomas and more frequently in women (70%) and non smokers (53.3%). CONCLUSIONS: ERCC1 expression was identified as positive (scores 2+ and 3+) in the majority of NSCLCs and seems to be an independent prognostic marker of longer survival. In addition EGFR expression was positive (scores 2+ and 3+) in the minority of NSCLCs and only in adenocarcinomas, more frequently in ERCC1-negative (scores 0 and 1+) tumors, suggesting that it is not an independent prognostic marker for the outcome of the patients suffering from NSCLC.

Cytopathologic interpretation of ascites due to malignancy.

The diagnosis of metastatic cancer in peritoneal fluid is of great importance for the patient and the attending physician. A cytopathologist's responsibility is twofold: (1) to accurately identify malignant cells; (2) to interpret tumor type and if possible the site of its origin even in the absence of complete clinical history of other clues. The difficulty in the diagnosis of metastatic neoplasms in peritoneal fluid is due to 2 factors: (1) abnormal mesothelial cells or macrophages may simulate cancer cells, or may conceal tumor cells; and (2) peritoneal fluid constitutes a natural and hitherto inadequately explored medium of cell culture, in which neoplastic cells may proliferate free of the boundaries imposed upon them by the framework of organs and tissues. Immunocytochemistry (ICC) and molecular techniques are essential to establish an accurate diagnosis. From a great many points of view malignant peritoneal fluid is suitable for continuous study of cancer cells, thus providing knowledge about biologic aspects of human solid tumors.

Cytologic diagnosis of spinal cord ependymoma in cerebrospinal fluid.

Ependymoma cells are known to rarely exfoliate into cerebrospinal fluid (CSF). However, the frequency of CSF involvement in patients with ependymoma is unclear, and to the author's knowledge the cytomorphologic features of tumour cells have not been well described to date. In this study, the CSF findings in a patient with ependymoma and the cytopathological features of this tumor are reported. The patient presented at the University Hospital of Heraklion, Crete, suffering from a chest to back pain. Computed tomography, scanning and magnetic resonance imaging (MRI) were performed and a mass of 3x2 cm in the thoracic aspect of the spinal cord was found. A sample of cerebrospinal fluid (CSF) was sent for cytologic examination and a diagnosis of ependymoma was made. A biopsy was performed and histology confirmed the cytologic diagnosis of ependymoma grade II (WHO). Exfoliated cells from ependymomas of spinal cord are rarely recognizable in CSF samples. Except in patients with myxopapillary tumours and anaplastic tumours, cytomorphologic features of ependymoma have been described only in case reports of intraoperative imprinting or fine needle aspiration biopsies (FNABs) and not in CSF cytology.

Apoptosis and cell proliferation correlated with tumour grade in peritoneal fluids of patients with serous ovarian cancer.

OBJECTIVE: Apoptosis and cell proliferation in peritoneal fluids of patients with ovarian serous adenocarcinoma have not been well described in cytology. To investigate the contribution of cell death to the growth of this tumour we analysed both apoptosis and cell proliferation in peritoneal fluids of patients with ovarian serous adenocarcinoma. METHODS: We studied 40 tumours from 40 patients with ovarian serous adenocarcinoma. Twelve tumours were high grade, 13 were moderately differentiated and 15 were poorly differentiated. The detection of DNA fragments in situ using the terminal deoxyribonucleotidy transferase (TDT)-mediated dUTP-digoxigenin nick-end labelling (TUNEL) assay was applied to investigate active cell death (apoptosis), and the MIB-1 antigen was used to investigate cell proliferation. RESULTS: The TUNEL indices were 0.29 ± 0.05, 0.79 ± 0.10 and 2.1 ± 0.90 in Grade I, Grade II and Grade III ovary carcinomas, respectively. The MIB-1 antigen labelling indices were 6.5 ± 0.09, 12.9 ± 3 and 25.8 ± 6.2, respectively, in the same order of tumour differentiation. The differences in both TUNEL and MIB-1 labelling indices were statistically significant between Grade I, Grade II and Grade III carcinomas and there was a positive correlation between the two indices (P < 0.001). CONCLUSIONS: Apoptosis and cell proliferation increased as the grade of tumour increased in ovarian serous adenocarcinoma, suggesting a rapid turnover of the tumour cells in tumours of higher grade, and may play an important role in the growth and the extension of such cancer cells in the peritoneal cavity.

Apoptosis and cell proliferation correlated with tumor grade in patients with lung adenocarcinoma.

BACKGROUND: Apoptosis and cell proliferation in patients with adenocarcinoma of the lung have not been well described with relation to fine-needle aspiration biopsies (FNABs). To investigate the contribution of apoptosis to the growth of adenocarcinoma of the lung, both apoptosis and cell proliferation were analysed for correlation with the grade of the tumor. PATIENTS AND METHODS: Fifty tumors from 50 patients with adenocarcinoma of the lung were studied. Twelve tumors were well-differentiated, 22 were moderately differentiated and 16 were poorly differentiated. The detection of DNA fragments in situ using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay was applied to investigate active cell death (apoptosis) and the MIB-1 antigen was used to investigate cell proliferation. RESULTS: The TUNEL indices were 0.55±0.09, 0.90±0.33 and 3.1±0.99 in well-, moderately and poorly differentiated adenocarcinoma of the lung respectively. The MIB-1 antigen labeling indices were 7.1±0.12, 14.3±3.5 and 28.7±6.9, respectively, in the same order of tumor differentiation. The differences in both TUNEL and MIB-1 labeling indices were significant between well-, moderately and poorly differentiated adenocarcinoma of the lung and a positive correlation was found between the TUNEL indices and the MIB-1 indices. CONCLUSION: Apoptosis (cell death) and cell proliferation increases as the grade of differentiation decreases in adenocarcinoma of the lung, suggesting a rapid turn over of the tumor cells in tumors with a lower grade of differentiation.

Endometriosis-associated Lyme disease.

The aim of this study is to report three cases of patients with endometriosis and infertility, and associated with Lyme disease. The medical files of 405 women with endometriosis and 200 without endometriosis were studied retrospectively. We report 3 cases with endometriosis and Lyme disease. Of 405 patients with endometriosis treated in our study over a 6-year period, 3(0.8%) had Lyme disease. All cases presented with typical erythema migraines, fever and fatigue. The serological findings were positive for Borrelia burgdorferi, for 3 cases. Two out of 3 women underwent IVF-ET procedures and one of them conceived in the first cycle without complication during pregnancy or after childbirth recorded. We concluded that women with endometriosis are more likely to have chronic fatigue syndrome, systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, multiple sclerosis, and other autoimmune inflammatory and endocrine diseases. A review of the literature confirms the uniqueness of the co-existence of Lyme disease in women with endometriosis in these cases.

Correlation of heat shock protein (HSP70) expression with cell proliferation (MIB1), estrogen receptors (ER) and clinicopathological variables in invasive ductal breast carcinomas.

The aim of our study was to evaluate the relationship between the expression of HSP70 protein, cell proliferation, the expression of ER receptors and the clinicopathological variables Grade and LNS in breast invasive human tumors along with the role of HSP70 protein in the prognosis of human breast cancer. A strong association between HSP70 expression and ER content, in agreement with previous data, was found which revealed a statistically significant association between HSP70 positivity and ER expression (p<0.008) in 50 cases of invasive primary human breast cancers. We also found a strong correlation between HSP70 expression, Grade and LNS of invasive ductal breast carcinomas. This suggests that the expression of HSP70 plays a significant role in the progression of human breast cancer, and might prove useful in many other malignancies as an important marker for the outcome of the disease.

HSP-70, C-myc and HLA-DR expression in patients with cutaneous malignant melanoma metastatic in lymph nodes.

HSP-70, C-myc and HLA-DR were examined in patients with cutaneous malignant melanoma metastatic to lymph nodes. Lymph-nodal fine-needle aspiration biopsies (FNABs) were analyzed and the results were correlated to other variables, such as the gender of the patients, Clark level and Breslow thickness of the primary tumor. Thirty cases of metastatic melanoma in lymph nodes from 30 patients with cutaneous malignant melanoma were studied. All patients (100%) had microscopic regional nodal metastasis and a recurrence of the lesion during the first two years. The HSP-70, C-myc and HLA-DR expressions were investigated immunocytologically, using the APAAP (alkaline phosphatase) method on the FNAB samples. The immunocytochemical expressions of HSP-70 protein, C-myc oncogene, and HLA-DR antigen were found in 18 cases (60%), in 14 cases (43.3%) and in 12 cases (40%), respectively. Clark levels were significantly associated with HSP-70 protein (< 0.01), C-myc oncogene expression (< 0.05) and HLA-DR antigen (< 0.01) expression. The HLA-DR antigen was also found to be related (< 0.05) to higher Breslow thickness (> 1.5 mm). The clinical course of malignant cutaneous melanoma is related to the expression of these indices, which seem to play a significant role in the metastasis and prognosis of this aggressive tumor. The immunocytochemical expression of HSP-70 in the malignant melanoma tumor could be of particular value in the identification of patients with poor prognosis.

Modulation of vascular endothelium by imatinib: a study on the EA.hy 926 endothelial cell line.

In this study the EA.hy 926 endothelial cell line--simulating endothelial cells--was treated with imatinib in order to define a possible anti-angiogenic role for imatinib. Dose and time response experiments were performed. Cell morphology was studied, while migration efficiency, intercellular permeability and VE-cadherin expression were assayed, both in the presence and in the absence of imatinib. Imatinib-induced EA.hy 926 cell apoptosis was also examined. Results showed that imatinib reduced the endothelial cell population, changed cell monolayer morphology and reduced cell-to-cell cohesiveness. Migration efficiency was significantly decreased while intercellular permeability was 2.76-fold increased in the presence of imatinib. Indirect immunofluorescence microscopy showed nearly complete down-regulation of VE cadherin in imatinib-treated cells. Furthermore, apoptotic activity was detected in imatinib-treated cells. Altogether our results support an antiangiogenic profile for imatinib that possibly contributes to its therapeutic potential.

Telomerase activity as a marker of invasive ductal breast carcinomas on FNABs and relationship to other prognostic variables.

To study the activity of telomerase and the relationship between telomerase and other prognostic variables in cases of invasive ductal breast carcinomas, fifty fine-needle aspiration biopsies (FNABs) obtained from the same number of female patients, diagnosed cytologically and confirmed histologically after surgery, were examined. The same cases were studied immunocytochemically using monoclonal antibodies to telomerase, estradiol receptors (ER) and HER-2 (CB11) and a standard alkaline phosphatase (APAAP) method. Telomerase activity was found in 72% of the carcinomas studied. An association was found between telomerase activity, ER receptors and HER-2 expression (p <0.005). A relationship between telomerase activity, histological grade and lymph node status (LNS) was found as well (p<0.005). The above results seem to be significant prognostic factors and should be taken into consideration in the follow-up of patients after appropriate treatment for breast cancer.

Topoisomerase II alpha expression in breast ductal invasive carcinomas and correlation with clinicopathological variables.

Topoisomerase II alpha (topo IIa) is an enzyme that in normal cells is expressed predominantly in the S/G2/M-phase of the cell cycle. In malignant cells, in vitro studies have indicated that the expression of topo II alpha is both higher and less dependent on the proliferation state in the cell. To study the expression of topo IIa and the relationship between that expression-and other variables in cases of breast ductal invasive carcinomas, 50 fine-needle aspiration biopsies were performed from the same number of female patients, diagnosed cytologically and confirmed histologically after surgery. The same cases were studied immunocytochemically using monoclonal antibodies to topo IIa and Her2/neu (CB11) by the alkaline phosphatase method (APAAP). Topo IIa was found in 32 cases (64%) of the carcinomas studied. An overexpression between topo IIa and Her2/neu was found (p < 0.005). A relationship between topo IIa expression, histological grade and lymph node status (LNs) was also found (p < 0.005). Increased topo IIa expression seems to be related to an aggressive form of breast cancer featuring Her2 amplification and lymph node metastasis.

Lens epithelial apoptosis and cell proliferation in human age-related cortical cataract.

PURPOSE: To probe the presence of apoptosis in the epithelium of human lenses with age-related cortical cataract as well as to assess cell proliferation, a predicted consequence of apoptotic cell death, in this specific cell population. METHODS: DNA fragmentation was assessed using terminal digoxigenin-labeled dUTP nick end labeling (TUNEL) in capsulotomy specimens obtained from patients who underwent either extracapsular cataract extraction for the removal of adult-onset cortical cataract (n=27) or clear lens extraction for the correction of high myopia (n=25). Cell proliferation was assayed in 23 epithelia of cataractous lenses, and 20 epithelia of non-cataractous lenses with the proliferation marker MIB1, a monoclonal antibody against the nuclear antigen Ki-67 that is detected throughout the cell cycle but is absent in the resting (G0) cell. RESULTS: TUNEL staining was observed in 25 (92.6%) specimens of cataractous lenses, whereas cells undergoing apoptosis were identified in 2 (8%) of the epithelia from non-cataractous lenses. Only two MIB1-positive samples were detected, one of which was a capsule obtained during intracapsular cataract extraction. CONCLUSIONS: The epithelium of human lenses with cortical cataract undergoes low rate apoptotic death. This limited epithelial apoptosis is unlikely to result in any significant cell density decrease since epithelial gaps are likely to be replaced by cell proliferation at the germinative zone of the anterior lens capsule. Nevertheless, the accumulation of small-scale epithelial losses during lifetime may induce alterations in lens fiber formation and homeostasis and result in loss of lens transparency.

First-line intra-arterial chemotherapy (IAC) with epirubicin and mitoxantrone in locally advanced breast cancer.

BACKGROUND: Approximately 20% of patients with breast cancer present with locally advanced disease without distant metastases. This phase II double-center trial aimed at investigating the activity of epirubicin (Farmorubicin)--mitoxantrone (Onkotrone/Novantrone) combination as first-line intra-arterial chemotherapy (IAC) in locally advanced breast cancer patients. PATIENTS AND METHODS: Thirty-six patients with locally advanced disease and no prior exposure to anthracyclines received the following regimen: epirubicin (Farmorubicin) 30 mg/mq and mitoxantrone (Onkotrone/Novantrone) 10 mg/mq by IAC short infusion on day 1, every 3 weeks for up to six cycles. Prior to IAC an arteriogram of subclavian, internal mammary and lateral thoracic arteries was obtained in all patients, followed by infusion of a blue dye solution into the arteries to determine the most appropriate vessel that supplies the tumor area. RESULTS: Objective responses, confirmed at least 4 weeks after the first documentation, were observed in 25 patients (70%; 95%CI, 62% to 80%): 3 CR, 22 PR. Although three of the patients showed complete tumor regression, operative removal or toilet mastectomy became feasible in 25 patients since tumor shrinkage ranged over 75%. A total of 25 mastectomies were carried out for 36 patients. Four patients had bulky tumors (> 13 cm tumor diameter), while 8 patients had ulcerated tumors, two of which presented with complete infiltration of normal breast tissue. The median time to progression and median overall survival were 11 and 27 months, respectively. The time to local response was 3 weeks and time to mastectomy was 9 weeks. Transient neurological disorders developed in six patients and skin chemical burns with painful inflammatory reactions were encountered in ten patients. No systemic toxicity was observed in terms of bone marrow depression and hair loss. No cardiotoxicity was observed. In all specimens necrosis was reported (complete 3 cases, partial 16 and minimal 6). CONCLUSION: A combination of epirubicin (Farmorubicin) and mitoxantrone (Onkotrone/Novantrone) as IAC appears to be a safe and well tolerated treatment for locally advanced breast cancer without clinical evidence of distant metastases. When combined with surgery it offers interesting results in terms of local control and allows a high rate of mastectomies in otherwise inoperable cases.