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.

THE PROGNOSTIC SIGNIFICANCE OF P53, BCL2 AND MIB1 EXPRESSIONS RELATED WITH OTHER CLINICOPATHOLOGICAL VARIABLES IN SEROUS OVARIAN CARCINOMAS. A CLINICOPATHOLOGICAL STUDY IN PERITONEAL FLUIDS.

OBJECTIVE: The first cytological study examining the expression of P53, BCL2 and MIB 1 expressions in correlation with other clinicopathological parameters in ascitic fluids of patients with serous ovarian carcinomas. MATERIALS AND METHODS: Fifty women 35-75 years old were diagnosed cytologically and confirmed histologically after operation in the University Hospital of Crete. All carcinomas were serous type and eight(8) of grade I, eighteen (18) of grade II and twenty two (22) of grade III. All carcinomas were staged according to the Figo criteria. Fifteen (15) were of Figo stage III and thirty five (35) were of Figo stage IV. For p53 and bcl-2, staining was evaluated on a semiquantitative scale depending on the number of cells showing positivity. For MIB1, the percentage of positive nuclei was calculated. Main outcome measure(s): The expression of P53, BCL2 and MIB 1 (Ki 67) correlated with tumor grade and Figo stages were estimated by chi-square (χ2). RESULTS: The expression of P53 and MIB1 were found to be statistically significant (p < 0.005) correlated with Figo stage and tumor grade. A statistical significant correlation was also found between BCL2 expression and tumor Grade ( p < 0.005) but not between BCL2 expression and Figo Stage. The study found a high expression of P53 (64%) and MIB1 (72%) and an expression of BCL2 (48%) in ascitic fluid of patients with ovarian carcinoma. A statistically significant correlation between P53 and MIB1 expression correlated with tumor grade and Figo stage (p < 0.005) and a statistically significant correlation between BCL2 expression and tumor grade but no with the Figo stage was found (p < 0.005). There was a positive correlation between P53 and MIB1. No significant association was found between P53 and BCL2 expression or MIB1 labeling index. CONCLUSION(S): Our data show significant differences in the expression of these markers in ovarian tumors and suggest a possible role for these tumor-associated genes as supplemental tools in prognosis and further definition of the biologic potential of these tumors.

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.

Touch imprint cytological diagnosis of nodal Langerhans cell histiocytosis.

Touch imprint cytological diagnosis of nodal Langerhans cell histiocytosis. Langerhans cell histiocytosis (LCH) is a rare neoplasm of the mononuclear phagocytic immunoregulatory system of unknown aetiology. Nodal involvement is uncommon. Cytological findings have seldom been described. A case study of LCH, arising in a submandibular node of a 42-year-old female, is reported. Fine needle aspiration smears were highly cellular and composed of a mixed cell population including eosinophils, lymphocytes, neutrophils, and macrophages. Imprint slides from the surgical specimen of the excised node exhibited Langerhans cells with nuclear grooves, leading to a diagnosis suggestive of LCH. Immunohistochemical staining of the node sections with CD1a and S-100 confirmed this diagnosis. In conclusion, cytology may favorably contribute to the diagnosis of LCH.

Liquid Based Preparation (LBP) cytology versus Conventional Cytology (CS) in FNA samples from breast, thyroid, salivary glands and soft tissues. Our experience in Crete (Greece).

BACKGROUND: The improvement in quality of cytological preparations with the use of LBP methodology has been well-documented, but the cytological artifacts resulting from this technique have not been adequately described. This study describes and illustrates the cytological artifacts introduced by LBP technique when used on fine-needle aspirates (FNAs), and evaluates these artifacts as potential diagnostic pitfalls. STUDY DESIGN: We reviewed a total of 96 FNAs simultaneously processed by both conventional smears and LBP. FNAs were obtained from the following sites: lymph node (38), breast (28), soft-tissue sites (nine), salivary glands (six), and thyroid gland (15). RESULTS: The LBP smears were consistently devoid of obscuring elements, and the cells were adequately preserved and evenly dispersed. However, we noted some cytomorphological alterations that should be recognized to avoid erroneous diagnoses. The size of cell clusters was decreased, large branching sheets were fragmented, and there were more single cells, resulting in apparent discohesion. Small cells such as lymphocytes tended to aggregate. All cells were generally smaller and occasionally spindled, the chromatin detail was attenuated, and nucleoli were more prominent. Intranuclear inclusions were difficult to visualize. Background matrix was often altered in both quantity and quality. Extracellular particles, small mononuclear cells, red blood cells, and myoepithelial cells were markedly decreased in number. CONCLUSIONS: Cytopathologists should be careful in interpreting FNAs prepared using LBP technique if that is the only methodology employed. Familiarity with artifacts is essential to avoid misdiagnoses.

Axillary nodal metastasis of occult breast primary cancer.

Occult breast cancer presenting with axillary metastases is an unusual presentation and can be a diagnostic and therapeutic challenge. A comprehensive work-up, including mammogram, sonogram, magnetic resonance imaging, and even pathologic examination of the mastectomy specimen may not disclose the primary tumor in up to one third of patients. We report a case of a 42-year-old female with occult breast cancer presenting axillary nodal metastasis. She complained of a swelling of the right axillary lymph node, but no breast mass was palpable. Biopsy of the lymph node was performed and histological examination showed a metastatic carcinoma. Estrogen receptor of the lymph node was positive. Calcifications were obtained by mammography and ultrasonography of the right axillary node contained metastasis. All these data suggested an occult carcinoma of the breast and modified radical mastectomy was performed. Pathological findings of the removed specimen failed to find the primary breast cancer lesion. Our case is one more example of this rare occurrence. We assume that the primary carcinoma is so small as to escape detection by histology. It is doubtful if mammography can help to localize these elusive lesions. More refined high resolution methods, are needed to solve this oncologic problem.

Neck nodal metastases from unknown primary: case series.

BACKGROUND: Neck nodal metastases from occult primary constitute about 5%-10% of all hosts harboring carcinoma of unknown primary site. Metastases in the upper and middle neck (levels I-II-III-IV-V) are generally attributed to head and neck cancers, whereas the lower neck (level IV) involvement is often associated with primaries below the clavicles. Diagnostic procedures include a careful clinical evaluation and a fiberoptic endoscopic examination of the head and neck mucosa, biopsies from all suspicious sites or blindly from the sites of possible origin of the primary, computerized tomography (CT) scan, and magnetic resonance radiology (MRI). The most frequent histological finding is squamous cell carcinoma, particularly when the upper neck is involved. SETTINGS: We report three cases of patients presented with nodal metastases of the neck from unknown primary site and we also describe the diagnostic and therapeutic approach employed in each one. RESULTS: One patient harbored a neuroendocrine metastatic deposit, the second patient a poorly differentiated carcinoma and the third one a malignant melanoma. CONCLUSIONS: Diagnostic procedures should be aimed at clarifying the histology of the nodal metastases and detecting the primary tumor site.

Fibroadenoma masquerading carcinoma on fine-needle aspiration of the breast.

OBJECTIVE: Benign and malignant lesions of the breast may have similar appearances on fine-needle aspiration cytology. We report a case of fibroadenoma that was diagnosed as carcinoma by cytology. CASE STUDY: Breast fine-needle aspiration biopsy was highly cellular and composed of bland-appearing spindle/columnar cells that could represent either epithelial or stromal cells; the case was reported as positive and the patient had subsequent excisional biopsy taken. RESULTS: On microscopic examination, smears were hypercellular and had many single cells and clusters of columnar/ elongate cells No obvious bipolar cells of myoepithelial origin were seen. Significant atypia was noted. Immunocytochemistry for smooth muscle actin was not performed due to insufficient material. CONCLUSIONS: Some cases of fibroadenoma and carcinoma can be very difficult to distinguish on fine needle aspiration cytology smears. Immunocytochemistry may be of help if sufficient material is provided. To avoid false positive diagnosis on cytology, it is best to report such a case as intermediate (atypical/suspicious) with final interpretation pending excisional biopsy.

Intraoperative touch imprint cytological analysis of sentinel lymph nodes for the presence of metastases in malignant melanoma.

AIM: Sentinel lymph node (SLN) biopsy has revolutionized lymph node staging in patients with malignant melanoma. Intraoperative evaluation is a new addition to the SLN procedure that allows for a one-step regional lymph node dissection to be performed when the SLN biopsy findings are positive. The discriminatory immunostaining pattern with the S-100 and HMB45 monoclonal antibodies allows intraoperative immunocytochemical evaluation of imprint smears of SLNs for melanoma metastases. METHODS: One hundred twenty eight SLNs from a cohort of 52 patient-cases that had been identified using sulfur colloid as a radioactive tracer and isosulfan blue were bisected for rapid Diff-Quick stained touch preparations. Intraopera-tive evaluation of sentinel node status by imprint cytology was correlated with the histopathological results of permanent sections. Tumor-negative nodes in routine paraffin sections were further investigated with the employment of the S-100 and HMB45 antibodies. RESULTS: Thirty-six of all SLNs harbored metastases in paraffin sections, from which 32 were identified by imprint cytology (sensitivity 88.8%). Three SLNs were positive by imprint cytology and negative by histopathology of paraffin sections. Comparison of the results of the touch preparations with the final histopathology (hematoxylin-eosin and S-100/ HMB45 stains) demonstrated a sensitivity of 83.3% and a negative predictive value of 92.5%. The specificity and positive predictive value were 100% respectively. CONCLUSION: Touch imprint cytology is potentially useful for intraoperative evaluation of SLNs in malignant melanoma patients. Results can be improved if the surface sampled is appropriately enlarged and a rapid immunohistochemical S-100/HMB45 stain on the imprints is utilized.

Thyroglossal duct cyst: case series.

OBJECTIVE: Thyroglossal duct cysts are remnants of the embryonic thyroglossal duct that may occur anywhere from the base of the tongue to the thyroid gland. The majority, however, are found at the level of the thyrohyoid membrane, under the deep cervical fascia. They are midline or just off the midline, and move up and down upon swallowing. This paper presents five case reports of TDC seen in the Department of Ear-Nose-Throat Surgery Regional Hospital Of Chania, Crete, Greece. It also discusses the different diagnostic approaches and differential diagnoses of the lesion. STUDY DESIGN: The medical records of patients admitted from 1995-2006 were reviewed for patients treated for TDC. History and examination reports were studied. When possible, results and reports of special investigations were obtained and the investigations were re-evaluated. Surgical operation notes and histology reports were obtained and the histologic slides were re-examined as necessary. RESULTS: Five cases of thyroglossal duct cyst treated in our department are described with each having a different clinical picture. CONCLUSIONS: Although the clinical and histological presentations of these five cases are not rare, they do illustrate how varied thyroglossal duct cysts can be with respect to patient age, anatomic site, or associated signs and symptoms.