Evaluation of aspiration cytology of ovarian masses with histopathological correlation

T. Sood, U. Handa, H. Mohan and P. Goel
Evaluation of aspiration cytology of ovarian masses with histopathological correlation Objectives: To evaluate the efficacy and diagnostic accuracy of fine needle aspiration cytology (FNAC) in distinguishing non‐neoplastic and neoplastic ovarian lesions and to determine reliable cytological criteria for typing neoplastic ovarian masses into benign and malignant tumours and their subtypes. Methods: FNAC was performed on 50 patients diagnosed as having an ovarian mass clinically and/or ultrasonographically. Detailed history, clinical examination and ultrasound findings in each case were recorded. The cytological diagnoses were categorized as neoplastic and non‐neoplastic and further into benign and malignant neoplasms. These cytological diagnoses were then compared subsequently with the histopathological diagnoses. Results: The study material consisted of 57 aspirates from 50 patients. A comparison of cytological findings with the histological diagnosis was possible in 53 aspirates; in the remaining four cases (7%) the smears were acellular. On cytology, 31 lesions were diagnosed as neoplastic and 22 as non‐neoplastic. The overall sensitivity of cytology in diagnosing neoplastic and non‐neoplastic ovarian lesions was 93.9% and the specificity was 100%. The positive predictive value was 100% and negative predictive value 90.9%. The overall diagnostic accuracy was 96.2 %. Conclusion: FNAC of ovarian masses is a minimally invasive procedure that can differentiate neoplastic from non‐neoplastic ovarian lesions. It may help avoid unnecessary operations and preserve the reproductive ability in young patients. Furthermore, it also enables a satisfactory sub‐categorization of ovarian tumours, which facilitates the choice of appropriate therapy.     

Aspiration cytology of 147 adnexal cysts with histologic correlation.

OBJECTIVE: To assess the usefulness of cytology in the diagnosis of 147 histologically established adnexal cysts. STUDY DESIGN: Retrospective, macro-microscopic study based on fluid aspirated from 132 ovarian and 15 extraovarian cysts and projected as a cytohistologic correlation. RESULTS: Typical macroscopic features were identified in 76% of endometriotic cysts, in 53% of mucinous neoplasms and in 67% of dermoid cysts. Cytology helped to identify 67% of nonneoplastic and 56% of neoplastic cysts. The lowest diagnostic sensitivities were observed in functional cysts and benign serous neoplasms (50%), while the highest were shown by endometriotic cysts (76%) and malignant epithelial neoplasms (71%). Inadequate samples were obtained from all types of cysts, even malignant ones (two mucinous cystadenocarcinomas). Diagnostic cytology was useless in extraovarian cysts (33% sensitivity). An adult granulosa cell tumor was erroneously diagnosed as a follicular cyst by cytologic examination. CONCLUSION: Examination of the cyst fluids obtained by aspiration demonstrated low sensitivity, with 43% of inadequate samples obtained from all types of cysts. Malignant cystic neoplasms may be overlooked in inadequate samples. Our study also revealed that specificity in this type of analysis is high in inadequate samples, provided that the technique is carried out correctly.     

Role of fine needle aspiration cytology in the diagnosis and management of Warthin’s tumour of the salivary glands

J. M. Viguer, B. Vicandi, J. A. Jiménez‐Heffernan, P. López‐Ferrer, P. González‐Peramato and C. Castillo
Role of fine needle aspiration cytology in the diagnosis and management of Warthin’s tumour of the salivary glands Objective: Local excision surgical procedures and non‐surgical conservative management are considered alternatives to superficial parotidectomy in the treatment and management of Warthin’s tumour (WT). Such therapeutic alternatives demand accurate diagnosis. In order to determine whether fine needle aspiration cytology (FNAC) is capable of rendering such a minimally invasive diagnosis, we evaluated its accuracy and diagnostic parameters in a large series of histologically proven cases of WT. Methods: A cytohistological study of 116 salivary tumours from 110 patients (four WT were bilateral) with a histological or cytological diagnosis of WT. Results: Histology confirmed the cytological diagnosis in 103 of 114 tumours (90.4%). Two tumours were incorrectly diagnosed on cytology as WT. In 11 cases of WT there was an erroneous or non‐representative cytological diagnosis. The sensitivity was 90.4%, and positive predictive value 98.1%. Regarding malignancy, there were three misdiagnoses. One tumour diagnosed as WT was a low‐grade mucoepidermoid carcinoma. Two cases considered ‘suspicious of squamous cell carcinoma’ corresponded to WT. After review, 81.3% of the cases of WT were considered typical and 18.7% non‐typical; all misdiagnoses were in the latter group. Cytological difficulties could be divided into three areas: (i) absence of one or more diagnostic components; (ii) ‘squamoid’ pattern; and (iii) mucinous metaplasia. Degenerated oncocytes were present in 65% of cases. Conclusions: FNAC offers the possibility of a reliable diagnosis of WT. Pathologists must pay attention to the squamous appearance of degenerated oncocytes. Cytology, when coupled with clinical and image findings, may permit conservative tumour management.     

Role of fine needle aspiration cytology in the diagnosis of soft tissue tumours

Fine needle aspiration cytology (FNAC) is a widely accepted safe, simple and rapid diagnostic procedure used in the examination of neoplastic and non‐neoplastic lesions of various locations. Since its introduction, FNAC has developed into an effective diagnostic tool practiced in a large majority of medical centres evaluating and treating oncological patients. The role of FNAC has been limited in the examination of primary soft tissue lesions, however, as many physicians working in this area recommended against using FNAC. An increasing use of minimally invasive diagnostic procedures in the last decade has resulted in a better acceptance of FNAC as a first‐line approach or as a complementary tool to core needle biopsy in the diagnosis of musculoskeletal lesions. This review discusses the role and value of FNAC in the evaluation and treatment of soft tissue tumours based on the experience gathered over the course of 48 years at the Sarcoma Center in Lund, Sweden. FNAC reports most often provide diagnostic information allowing the initiation of treatment or, when definitive diagnosis cannot be rendered from a cytological examination, guiding the continued diagnostic investigation. The main advantages of soft tissue FNAC are good sensitivity and specificity, low morbidity, speed of diagnosis, and low cost/benefit ratio. The most important disadvantages stem from limited experience in cytological diagnosis of soft tissue tumours and a lack of standardised and uniform reporting system for soft tissue FNAC.     

Stereotactic biopsy and cytological diagnosis of solid and cystic intracranial lesions

Cytological smears from 115 consecutive cases of stereotactic biopsies of intracranial lesions were reviewed. Ninety-five lesions were solid and 20 cystic. Material from 90 solid and 13 cystic lesions was sent both for cytological and histological examination. In 66 of the solid lesions, the cytological diagnosis was confirmed by histology (five were benign lesions and 61 malignant tumours: 56 primary brain tumours, three metastases and two lymphomas). In 24 cases with discrepant cytology and histology, the histology was inconclusive or insufficient in 14 cases, while cytology established the diagnosis of astrocytoma grade II (seven cases), metastases (two cases), gliosis (one case) and benign (four cases). Necrosis of tumour type was observed cytologically in six patients representing glioblastoma (two cases), anaplastic astrocytoma (one case), lymphoma (one case) and normal brain (two cases) histologically. Three cases reported cytologically as benign were primary brain tumour (two cases) and gliosis (one case). One smear of a glioblastoma was insufficient for cytological diagnosis. Cystic lesions were cytologically benign in 17 cases and malignant in three cases. Histology from the cyst wall confirmed the malignant diagnosis in three cases and showed tumour in six more cases, a benign process (two cases), changes induced by radiotherapy for arteriovenous malformation (one case) and insufficient material (one case). In conclusion, cytology from solid brain lesion allows an accurate diagnosis and subtyping of tumours in a majority of cases, and can thus be used to choose type of therapy. In cystic brain tumours, however, examination of the cystic fluid, is often inconclusive and a biopsy from the cyst wall should be performed if there is clinical or radiological suspicion of tumour.     

The plasticity of germ cell cancers and its dependence on the cellular microenvironment

So far, the understanding of germ cell cancer (GCC) pathogenesis is based on a model, where seminomas and non‐seminomas represent distinct entities although originating from a common precursor termed germ cell neoplasia in situ (GCNIS). Embryonal carcinomas (ECs), the stem cell population of the non‐seminomas, is pluri‐ to totipotent and able to differentiate into cells of all three germ layers, giving rise to teratomas or tumours mimicking extraembryonic tissues (yolk sac tumours, choriocarcinomas). With regard to gene expression, (epi)genetics and histology, seminomas are highly similar to GCNIS and primordial germ cells, but limited in development. It remains elusive, whether this block in differentiation is controlled by cell intrinsic mechanisms or by signals from the surrounding microenvironment. Here, we reviewed the recent literature emphasizing the plasticity of GCCs, especially of seminomas. We propose that this plasticity is controlled by the microenvironment, allowing seminomas to transit into an EC or mixed non‐seminoma and vice versa. We discuss several mechanisms and routes of reprogramming that might be responsible for this change in the cell fate. We finally integrate this plasticity into a new model of GCC pathogenesis, allowing for an alternative view on the dynamics of GCC development and progression.     

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA): experience of an academic centre in the USA

S. Zhang, D. V. S. DeFrias, R. Alasadi and R. Nayar
Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA): experience of an academic centre in the USA Objectives: Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) has become widely accepted as an effective modality for obtaining tissue for primary diagnosis and staging. We have been using EUS‐FNA since July 2001 and herein we summarize our experience over a 5‐year period. Methods: A computer‐based search for in‐house EUS‐FNA was performed in the pathology database from July 2001 to October 2006. To calculate the sensitivity, specificity and accuracy of EUS‐FNA, the cytology diagnosis was compared with the surgical follow‐up. Results: A total of 951 EUS‐FNAs were performed during the study period and included 279 pancreatic solid lesions, 186 pancreatic cyst lesions, 249 lymph node aspirations, 111 gastrointestinal (GI) tract submucosal lesions, and 126 miscellaneous lesions. EUS‐FNA had a very high sensitivity and accuracy for solid pancreatic lesions (94.7 and 97.7%, respectively), low sensitivity and accuracy but high specificity (47, 64.8 and 95%, respectively) for cystic lesions. Cyst fluid carcinoembryonic (CEA) levels were significantly higher in mucinous neoplasms than non‐neoplastic cysts. EUS‐FNA also had very high sensitivity and specificity for detecting metastatic carcinoma in lymph nodes (95 and 100%, respectively). GI submucosal spindle cell tumours were further classified with immunohistochemical stains performed either on a cell block or a core biopsy obtained via EUS guidance. Conclusions: EUS‐FNA has a very high sensitivity and accuracy for pancreatic solid lesions, but the sensitivity for cystic lesions is generally low. Cyst fluid chemical analysis for CEA is helpful, but the overlap between mucinous neoplasm and non‐neoplastic cysts is significant. Recognizing GI contamination is important and immunohistochemical stains are useful for GI submucosal spindle cell lesions.     

Cytological diagnosis of soft tissue tumours

Cytological diagnosis of soft tissue tumours The aims of this study were to determine the patterns of soft tissue tumours and also to try to assess the utility of fine needle aspiration cytology (FNAC) in diagnosing soft tissue tumours. Of 15 361 patients who visited the cytology diagnostic service of the Pathology Department, Medical Faculty, Addis Ababa University, 623 (4.1%) cases with a diagnosis of soft tissue tumours were retrieved from the department's records for the years 1991-96. Fifty-three soft tissue tumours (25 benign and 28 malignant tumours) with combined FNAC and surgical biopsy results were traced for cyto-histological correlations. Twenty-two out of 25 benign soft tissue tumours were correctly diagnosed, with three false cytologic diagnoses where one mesenchmal neoplasm, one haemangioma, and one haemorragic lesion were identified; and out of 28 malignant soft tissue, 23 were correctly diagnosed however, the five false cytological diagnoses were one soft tissue sarcoma, one dermatofibrosarcoma, one malignant mesenchymal neoplasm, one spindle cell neoplasm and one menechymal neoplasm. Thus, in this study a sensitivity and specificity of 88.5% and 81.5% respectively for the diagnosis of soft tissue tumours were reported. In conclusion, FNAC of soft tissue tumours is a fast, effective and reliable diagnostic tool that may help in categorizing soft tissue tumours into benign and malignant groups for clinical management.     

Importance of FNAC in the detection of tumours within multinodular goitre of the thyroid

The primary challenge in the management of a multinodular thyroid gland is to rule out malignancy. The present study was undertaken to assess the value of preoperative ultrasound-guided fine needle aspiration cytology (FNAC) in diagnosing tumours of the thyroid gland. Of the 80 patients operated for multinodular lesions, malignant tumours were found in 29 and benign tumours in 36 patients (81%) and non-tumorous lesions in 15 (19%) patients. Compared with the histopathological postoperative diagnosis, the overall sensitivity of FNAC was 85% and specificity 88%. Current morphological diagnosis of the nodules in multinodular goitre requires thorough preoperative examination, including ultrasound-guided FNAC in order to establish the appropriate management.     

Neural tumours of the neck presenting as thyroid nodules: a report of three cases

OBJECTIVES: Neural tumours of the neck may at times secondarily involve the thyroid and manifest clinically as thyroid nodules. On cytological evaluation these nodules may be confused with other spindle lesions of the thyroid. We report two cases of schwannoma and one case of a malignant peripheral nerve sheath tumour (MPNST) of the neck, which presented as thyroid nodules and evaluate the role of cytology in identifying these tumours. METHODS: The thyroid nodules in all the three cases were sampled by the non-aspiration technique using a 23-gauge needle. Both alcohol-fixed and air-dried smears were prepared and stained by the Papanicolaou and May-Grünwald-Giemsa stains. Cytology smears and histology sections from the resected specimens were reviewed, and the findings noted. RESULTS: Both the cases of schwannoma were correctly identified on cytology while the case of MPNST could only be typed as a spindle cell tumour. However, on cytology it was not possible to state whether the tumours were thyroidal or extrathyroidal in origin. CONCLUSIONS: Schwannomas of the neck are easily identifiable on cytology compared with MPNST. However, cytology alone is not helpful in identifying the origin of these tumours. As primary neural tumours of the thyroid are rare, the possibility of a soft tissue neural tumour extending into the thyroid should always be ruled out while evaluating these cases.     

Difficulties in diagnosing small round cell tumours of childhood from fine needle aspiration cytology samples

There are four basic reasons for the difficulties in diagnosing small round cell tumours (SRCT) in childhood from fine needle aspiration cytology (FNAC) samples. First, SRCTs are rare and it is difficult for cytopathologists to obtain enough experience for rendering reliable diagnoses. Second, SRCTs are morphologically very similar. Third, many SRCTs do not have specific antigens which could be demonstrated with immunocytochemistry (ICC) or they lose them when poorly differentiated. In addition, cross reactivity exists between some SRCTs. Unstandardized performance of ICC also contributes to the difficulties due to unreliable results. Fourth, suboptimal FNAC samples add additional pitfalls. The latter may be due to partly degenerate samples or to unrepresentative ones in cases where a SRCT is a heterologous component of another nosological entity. Lymphoma, neuroblastoma, nephroblastoma, Ewing's tumour/primitive neuroendocrine tumours and rhabdomyosarcoma are discussed in detail, while other less common SRCTs are mentioned as differential diagnoses when appropriate. The use of cytogenetic and molecular techniques for differentiating between certain SRCTs is helpful in some doubtful cases. However, there are still problems in the use of these techniques, especially their cost which may delay their being introduced in every cytopathology laboratory.     

Fine needle aspiration cytology in the diagnosis of bone lesions

OBJECTIVE: Fine needle aspiration cytology (FNAC) in combination with radiological examination has recently gained clinical recognition for evaluating skeletal lesions. We evaluated our experience with the use of FNA in diagnosing bone lesions with emphasis on areas of difficulty and limitations. MATERIALS AND METHODS: Over a period of 5 years FNA was performed in 66 cases of bone lesions. Aspirations were done by cytopathologists using 22-gauge needle. Out of 66 cases unsatisfactory aspirate was obtained in 12 cases. Cytohistological correlation was available in 19 cases. RESULTS: Adequate aspirates were categorized into neoplastic (27 cases) and non-neoplastic (27 cases) lesions. Of the 27 neoplastic aspirates, 20 were malignant (12 primary, 8 metastatic deposits) and 7 were benign. In the malignant group osteosarcoma was correctly diagnosed in 3 cases while other 3 were labeled as sarcoma NOS because of lack of osteoid. Metastatic deposits were sub-typed in 6 cases; from renal cell carcinoma (3 cases), proststic adenocarcinoma, follicular carcinoma thyroid, and squamous cell carcinoma. Neoplastic group comprised of 6 cases of cysts and 21 cases of chronic osteomyelitis. Thirteen cases were diagnosed as tuberculous osteomyelitis. CONCLUSIONS: FNA is a frequent indication in metastases in the bone where distinct cytologic features can even identify an unknown primary. However, diagnosis of primary tumours of the bone is limited by precise subtyping of the tumours. FNA has emerged as a cost effective tool for initial diagnosis of both neoplastic and non-neoplastic lesions of the bone.     

Fine needle aspiration biopsy of three cases of squamous cell carcinoma presenting as a thyroid mass: cytological findings and differential diagnosis

M. Rosa and K. Toronczyk Fine needle aspiration biopsy of three cases of squamous cell carcinoma presenting as a thyroid mass: cytological findings and differential diagnosis Objective: Primary squamous cell carcinomas of the thyroid gland are extremely rare, comprising about 1% of thyroid malignancies. Although squamous cell carcinomas are readily identified as such on aspiration cytology in the majority of cases, the differentiation of primary versus metastatic tumour might not always be easy. Herein, we report three cases of squamous cell carcinomas involving the thyroid gland. Methods: Fine needle aspiration cytology (FNAC) was performed in three patients with a thyroid mass using standard guidelines. Smears were stained with Diff‐Quik and Papanicolaou stains. Results: Two patients were male and one was female, aged 59, 45 and 35 years, respectively. In all three patients a thyroid mass was present. FNAC smears in all cases showed cytological features of squamous cell carcinoma including keratinization and necrosis. After clinical and cytological correlation, one case appeared to be primary, one case metastatic, and in the third case no additional clinical information or biopsy follow‐up was available for further characterization. Conclusions: Because primary squamous cell carcinoma of the thyroid is a rare finding, metastatic squamous cell carcinoma should always be excluded first. Metastatic disease usually presents in the setting of widespread malignancy, therefore a dedicated clinical and radiological investigation is necessary in these cases. In both clinical scenarios the patient’s prognosis is poor.     

Fine Needle Aspiration Cytology of Cutaneous Vascular Tumours

We have studied 12 cutaneous vascular tumours by means of fine-needle aspiration cytology (FNAC): six capillary haemangiomas, one cavernous haemangioma, one Masson's pseudo-angiosarcoma, two angiosarcomas, one benign haemangioendothelioma and one glomus tumour. We describe the main cytopathological findings and we discuss the differential diagnosis in each case. We consider that the cytopathological findings of the above lesions, evaluated in the context of the clinical findings, are sufficiently characteristic for us to be able to make a definitive diagnosis. We believe that FNAC can play an important part in the diagnosis and therapeutic planning of these tumours.     

Fine needle aspiration cytology of basal cell adenoma of the salivary gland: a cytohistological correlation study of 35 cases

B. Vicandi, J.A. Jiménez‐Heffernan, P. López‐Ferrer, P. González‐Peramato, M. Patrón and J.M. Viguer
Fine needle aspiration cytology of basal cell adenoma of the salivary gland: a cytohistological correlation study of 35 cases Objective: In order to evaluate the possibility of a specific cytological recognition of basal cell adenoma (BCA) we reviewed our experience with 35 histologically proven cases. Few series describing cytological features of BCA are available and diagnostic cytological criteria are not well established. Methods: This study was based on 41 cytology samples from 35 patients with BCA. Thirty‐five aspiration procedures were performed pre‐operatively and six on tumour recurrence. Nineteen of the 35 patients were men and 16 women. The mean age at diagnosis was 55 years old (range 24–92). The series includes one non‐representative case. Except for one tumour located in the upper lip, all of them involved the parotid gland. Results: Aspirates were cellular, showing groups with dense, homogeneous metachromatic stroma and single cells. Relevant features were the trident‐like configuration of groups, intimate relationship between neoplastic cells and stroma and cellular polymorphism. In approximately half of the cases a precise diagnosis was given. Most of the remaining tumours were diagnosed as benign but they were difficult to differentiate from pleomorphic adenoma. Regarding malignancy, there were two misdiagnoses of acinic cell carcinoma, due to high epithelial cellularity along with scarcity of stroma, and one case was considered to be suspicious of malignancy. Conclusion: BCA shows characteristic cytological features that allow a precise diagnosis. The main differential diagnosis is epithelial‐rich pleomorphic adenoma, while acinic cell carcinoma is a potential false positive.     

Posters. P17 Accuracy of fine needle aspiration cytology in diagnosis of thyroid swellings

Introduction Fine needle aspiration cytology is regarded as the gold standard investigation in diagnosis of thyroid swellings. Published data suggest an overall accuracy rate of 75% 1 in the detection of thyroid malignancy. The aim of this study was to determine the accuracy of FNA cytology in detection of thyroid malignancy in our surgical unit. Methods Between 1989–2002, 144 patients who underwent thyroid resection by single consultant surgeon and who had pre‐operative FNA were enrolled in this retrospective study. The pre‐operative FNA results were compared with definitive histological diagnosis following thyroid resection. Fine needle aspiration cytology was performed using aspirate and non‐aspirate techniques on each thyroid swelling. The cytological sample was assessed by a single cytopathologist and was classified as inadequate, non‐neoplastic, neoplastic, suspicious or indeterminate. The histology was classified as non‐neoplastic (benign) and neoplastic (malignant). Results Fine needle aspiration cytology analysis revealed 94 (13.88%) non‐neoplastic, six (65.27%) neoplastic and 20 (4.16%) suspicious aspirates. Twenty (13.88%) samples were inadequate and four (2.77%) samples were indeterminate. Histological analysis showed 118 (81.94%) benign, 26 (18.05%) malignant specimens. Fine needle aspiration cytology had a sensitivity, specificity and accuracy rate of 52.6%, 86.6% and 79.1%, respectively for diagnosing thyroid malignancy. Conclusion The results are comparable with the current published data and demonstrate that FNA cytology in our hands is accurate investigation for pre‐operative diagnosis for the detection of thyroid malignancy.     

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

A. Kalogeraki, I. Karvela‐Kalogeraki, P. E. Petraki, I. Zois, D. Tamiolakis and E. N. Stathopoulos
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.