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Villoglandular adenocarcinoma of cervix--a tumour with bland cytological features: report of a case missed on cytology

Jayaram G, Razak A

Malays J Pathol, 2003 Dec;25(2):139-43.
PMID: 16196371

The diagnosis of villoglandular adenocarcinoma of cervix on cytological smears is often missed due to the relatively bland cytological features of this tumour. A 45-year-old female with an exophytic cervical growth had three cervical smears reported as unsatisfactory. A cervical biopsy followed by Wertheim's hysterectomy showed a villoglandular adenocarcinoma (VGA) of cervix. Vaginal recurrence of VGA was again missed on the first post-operative vault smear. The second and third vault smears showed characteristic features of VGA that enabled correct identification. Review of some of the smears previously reported as unsatisfactory showed architectural features of VGA in the three dimensional (3-D) fragments that were previously considered to be benign.
The value of cytology in granulomatous mastitis: a report of 16 cases from Malaysia

Yip CH, Jayaram G, Swain M

Aust N Z J Surg, 2000 Feb;70(2):103-5.
PMID: 10711470

BACKGROUND: Granulomatous mastitis is a rare condition of the breast that can mimic a carcinoma. There are characteristic histological features, the most important of which is a predominantly lobular inflammatory process. It must be differentiated from known causes of granulomatous inflammation, such as tuberculosis.
METHODS: In the present paper, the clinical and pathological features of 16 patients with granulomatous mastitis seen over a 3-year period in the University Hospital, Kuala Lumpur, are described.
RESULTS: A clinical suspicion of malignancy was present in 10 cases. One of the patients was nulliparous. One had an associated hyperprolactinaemia, while two had systemic lupus erythromatosis. One of the patients was pregnant at the time of presentation. Four patients had localized lumps excised, five were treated conservatively because the lesion was too extensive to resect, and seven patients required drainage procedures for abscess formation.
CONCLUSION: Awareness of this condition is important because it mimics a carcinoma, and surgery may not be the best treatment for recurrent disease.
Fulltext The experience with fine needle aspiration cytology in the management of palpable breast lumps in the University Hospital Kuala Lumpur

Yip CH, Jayaram G, Alhady SF

Med J Malaysia, 2000 Sep;55(3):363-7.
PMID: 11200718

A total of 676 palpable breast lumps seen in the Breast Clinic, University Hospital, Kuala Lumpur from August 1993 to August 1994 were subjected to fine needle aspiration cytology. Fifty-four were reported as inadequate, 501 benign, 95 malignant and 26 suspicious. One hundred and eighty-seven aspirates had histological correlation, while 34 of the malignant aspirates had clinical correlation. The majority of the other 455 patients were followed up for a period of 60 to 72 months without any malignancies becoming apparent. For analysis, only the 221 cases with histological or clinical correlation were included, (the suspicious category was included into the positive group and the inadequate cases were excluded), giving a sensitivity of 91.7%, a specificity of 91.7% and a diagnostic accuracy of 91.7%. Breast cytology was an accurate and rapid method of diagnosis of breast diseases, and in a busy surgical unit with limited operating time, it allowed for the triage of patients with breast complaints in deciding which cases needed early open biopsy. A negative cytology does not exclude the possibility of cancer, as there was a false negative rate of 11%. However by utilising a diagnostic triad of clinical examination, radiological assessment and fine needle aspiration cytology, the risk of missing a malignancy is small.
The diagnostic usefulness of tumour markers CEA and CA-125 in pleural effusion

Sthaneshwar P, Yap SF, Jayaram G

Malays J Pathol, 2002 Jun;24(1):53-8.
PMID: 16329556

Pleural effusion is a common diagnostic problem. The analysis of serum and pleural fluid for tumour markers is widely used as a diagnostic aid in clinical practice. The aim of the present study was to determine the usefulness of simultaneous quantification of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA-125) in distinction of malignant from benign effusion. Data from a total of 78 patients including 53 patients with benign and 25 patients with malignant effusion was evaluated. The cut-off values for differentiating benign from malignant effusions were determined using results obtained from patients with known benign effusions (mean + 2 SD, 95% confidence interval). The cut-off for CEA and CA-125 were 5.1 ng/ml and 1707 IU/ml respectively. CEA assay in pleural fluid had an acceptable sensitivity and good specificity of 64% and 98% respectively. CA-125 had a sensitivity of 36% and specificity of 94%. The combination of the two tumour markers gave a sensitivity of 72% and specificity of 92.4%. We suggest a good clinical strategy may be to begin with CEA measurement (assay specificity 98%); if CEA is below the cut-off value (negative), CA-125 could then be measured to improve the sensitivity of detection of malignant effusions. However, measurement of these tumour markers is not cost effective from the point of view that it does not give information on the type of malignancy present. The latter has to be determined either by histological or cytological study.
Fulltext The Breast Clinic in University Hospital--a four-month survey

Yip CH, Alhady SF, Jayaram G

Med J Malaysia, 1995 Sep;50(3):268-71.
PMID: 8926907

The breast clinic in the university Hospital Kuala Lumpur was started in August 1993 to cater for the increasing number of women seeking treatment for breast complaints. A four-month survey carried out from January to April 1994 found that Chinese women are more "breast conscious" than Malay and Indian women. The majority of patients were in the reproductive age group. Benign breast diseases form the majority of cases of breast diseases seen. The pick-up rate for new cases of breast cancer was 3.1%. Fine needle aspiration biopsy had a 100% sensitivity during the four-month study, and was a quick method of obtaining a diagnosis.

Study site: Breast clinic, University Malaya Medical Centre (UMMC)
Fulltext Prostate-specific antigen in breast disease

Poh BH, Jayaram G, Sthaneshwar P, Yip CH

Malays J Pathol, 2008 Jun;30(1):43-51.
PMID: 19108411 MyJurnal

The aim of this study is to assess tissue and serum prostate-specific antigen (PSA) in breast lesions; to compare tissue PSA with serum PSA; to compare tissue PSA in benign and malignant lesions and to compare PSA with known prognostic factors in breast carcinoma. Tissue PSA immunoreactivity in twenty women with breast carcinoma was compared with PSA in twenty-three women with benign breast lesions. Tissue PSA was also compared with known prognostic indicators such as tumour size, axillary nodal status, histological type, histological grade, oestrogen receptor status, progesterone receptor status and c-erbB-2 oncoprotein over-expression. Serum free PSAlevels from these women were measured pre- and post-operatively and an attempt was made to correlate serum PSA with tissue PSA expression. 40% and 43% of malignant and benign breast lesions respectively showed tissue PSA immunoreactivity. No significant difference was observed in the tissue PSA expression between these two groups as also between tissue PSA and known prognostic indicators. As serum PSA levels were below the detection limit (< 0.004 ng/ml) in all except two benign cases, no statistical evaluation was done for the latter. Tissue PSA expression did not correlate with other prognostic markers and detectable serum PSA levels were present in too few cases for statistical analysis. Although no definitive conclusion is possible in this preliminary study regarding the role of PSA in breast disease, it stimulates interest in further research in this direction.
Papillary cystic type of acinic cell carcinoma of parotid: fine needle aspiration cytological features of a high grade variant with oncocytic metaplasia

Jayaram G, Othman MA, Kumar M, Krishnan G

Malays J Pathol, 2002 Dec;24(2):107-12.
PMID: 12887170

A 60-year-old female developed a right parotid swelling six months after surgery for intra-oral squamous cell carcinoma. Fine needle aspiration (FNA) cytological smears showed dissociated large and small pleomorphic tumour cells with abundant mitoses and oncocytic features. A cytological diagnosis of parotid acinic cell carcinoma (ACC) was made. Histological study of the subtotal parotidectomy specimen showed a papillary cystic variety of acinic cell carcinoma (ACC-PCV). FNA cytological features in this case of ACC-PCV differs from the two previously reported cases in that it showed prominent oncocytic and high grade features and absence of papillary pattern in the cytological smears. ACC-PCV is an uncommon tumour and knowledge of its varied FNA cytological features is important for the diagnosis of this neoplasm.
Papillary carcinoma arising in a thyroglossal duct cyst

Jayalakshmi P, Prepageran N, Jayaram G, Gopalakrishnan

Malays J Pathol, 2002 Jun;24(1):67-70.
PMID: 16329558

A 21-year-old lady was admitted with a one year history of painless swelling in the neck. The clinical features and radiological findings suggested a thyroglossal duct cyst. Histology of the excised duct cyst showed papillary carcinoma. Ultrasound examination of the thyroid gland was normal. The patient is on regular follow-up and is well two years following surgery.
Papillary breast lesions diagnosed on cytology. Profile of 65 cases

Jayaram G, Elsayed EM, Yaccob RB

Acta Cytol., 2007 Jan-Feb;51(1):3-8.
PMID: 17328487

OBJECTIVE: To analyze the cytologic features of nipple discharge and fine needle aspiration (FNA) cytologic smears from breast lesions reported as showing papillary features and to correlate them with histopathologic features.

STUDY DESIGN: The study group consisted of FNA smears and/or nipple discharge smears from 65 breast lesions diagnosed on cytology as duct papilloma, papillary lesion, fibrocystic condition, fibroadenoma, papillary neoplasm or papillary carcinoma. Cytomorphologic features assessed included cellularity, cell pattern (clusters, papillary, 3-dimensionality, etc.) and cell characteristics (monomorphism, pleomorphism, apocrine change, plasmacytoid features). Histological material was available for review and cytohistologic correlation in all cases.

RESULTS: Forty-six specimens were FNA smears, and 16 were nipple discharge smears; in 3 cases FNA and nipple discharge cytologic smears were available for review. Cytologic study could predict the presence of a papillary pattern in all neoplasms with pure or focal papillary differentiation. There was an overlap in cytomorphologic features between papillary and nonpapillary benign lesions as well as between benign and malignant papillary neoplasms. Frank blood in the aspirate, cell dissociation and atypia, however, were more frequent in the last.

CONCLUSION: Overlap of cytologic features in nonneoplastic and neoplastic benign papillary lesions and between benign and malignant papillary neoplasms necessitates histologic evaluation in all cases diagnosed as papillary on cytology. Since 49.2% of lesions showing papillary features on cytology prove to be malignant, all cases reported as papillary on cytology should be excised urgently for histologic assessment.
Nucleolar organizer regions distribution in fine needle aspiration cytological smears from breast lesions

Hasnan J, Jayaram G

Malays J Pathol, 1996 Jun;18(1):35-41.
PMID: 10879223

Fine needle aspiration (FNA) cytology is now an integral part of the pre-operative investigation of breast lesions and the therapeutic protocol is today often planned on the basis of cytodiagnosis. However, from time to time the cytological picture may be equivocal or inconclusive. In recent years, nucleolar organizer region (NOR) scores have been explored for potential value in the diagnosis of malignancy as the scores in malignant nuclei are seen to be higher than in benign or reactive nuclei. With a view to applying NOR scoring in the evaluation of cytologically equivocal cases, we adopted the argyrophil technique for staining NOR s (AgNOR) in FNA cytological smears of 56 breast lesions, comprising 31 benign and 25 malignant lesions. Histological correlation was possible in 26 of these cases (17 malignant and 9 benign) and AgNOR scoring was done on paraffin sections of these as well. There was a significant difference between mean AgNOR scores in benign and malignant lesions in the cytological smears (P < 0.001). The AgNOR scores ranged from 2.5 to 5.0 per cell in benign lesions and 5.8 to 17.2 per cell in malignant lesions. None of the cases fell into the gray zone of overlap. One malignant lesion that was cytologically equivocal showed a mean AgNOR score of 6.08. The AgNOR scores on histological sections also showed a statistically significant difference (P < 0.001) between benign and malignant lesions with mean scores ranging from 1.34 to 2.58 dots per cell in benign lesions and scores of 2.42 to 5.28 dots per cell in malignant lesions. However, the scores overlapped in four cases and therefore it was considered unsuitable for routine diagnostic work. From this preliminary study, we conclude that an FNA AgNOR score of 5.0 and less strongly favours a benign lesion whereas a score above 5.0 would be in favour of a malignant lesion. A larger study would be needed to verify our impression that AgNOR scoring can be useful in cytologically equivocal cases.
Mucoepidermoid carcinoma of the thyroid: a case report

Jayaram G, Wong KT, Jalaludin MA

Malays J Pathol, 1998 Jun;20(1):45-8.
PMID: 10879264

Primary mucoepidermoid carcinoma (MEC) of thyroid is an uncommon tumour and reports on its' cytology are consequently scanty. A 46-year-old male presented with a thyroid nodule of nine months duration. Fine needle aspiration (FNA) cytology of the nodule showed features of a malignant tumor that was different from the usual types of thyroid carcinoma. Monolayers and syncytial clusters of round and spindle tumour cells with large vesicular nuclei and single macronucleoli were present. A diagnosis of carcinoma was given with the comment that this was unlike any of the usual types of thyroid cancer and that a metastatic malignancy should be ruled out. The cytological picture of MEC may not always be distinctive enough for accurate tumour typing. Nevertheless the cytological features are usually sufficiently different to rule out all of the usual types of thyroid carcinoma. This distinction may be important from the point of view of differing prognosis in MEC of thyroid (as compared to differentiated thyroid cancers) and the need to exclude a metastatic carcinoma, especially from a primary in one of the salivary glands.
Mucinous carcinoma (colloid carcinoma) of the lung diagnosed by fine needle aspiration cytology: a case report

Jayaram G, Yaccob R, Liam CK

Malays J Pathol, 2003 Jun;25(1):63-8.
PMID: 16196380

Mucinous carcinoma of the lung, also known as colloid carcinoma, is an uncommon tumour that is rarely encountered in fine needle aspiration (FNA) cytological practice. A 64-year-old Chinese male presenting with blood stained sputum and hoarseness of voice was discovered to have a 3 cm sized mass in the left lung. Neither bronchial washings nor transthoracic FNA yielded positive results at this stage. Six months later the patient returned to the hospital with a larger tumour and mediastinal lymphadenopathy. Transbronchial lymph node FNA, reported as negative for malignancy showed normal, hyperplastic and mildly atypical bronchial epithelial cells as well as a few single cells and extracellular mucin. Transthoracic FNA of the lung lesion performed under computed tomographic guidance showed characteristic cytological features of this tumour, establishing the diagnosis.
Microfilaria in hydrocele fluid cytology

Chandran PA, Jayaram G, Mahmud R, Anuar AK

Malays J Pathol, 2004 Dec;26(2):119-23.
PMID: 16329565

Filariasis, a parasitic infection endemic in parts of India, Myanmar, islands of the South Pacific, West and East Africa and Saudi Arabia can be diagnosed from various types of cytopathological specimens. This case documents the detection of filarial infection from hydrocele fluid cytology in a 30-year-old Myanmar migrant worker in Malaysia.
Malignant teratoma of the thyroid with predominantly neuroepithelial differentiation. Fine needle aspiration cytologic, histologic and immunocytochemical features of a case

Jayaram G, Cheah PL, Yip CH

Acta Cytol., 2000 May-Jun;44(3):375-9.
PMID: 10833994

BACKGROUND: Teratoma of the thyroid in adults is extremely rare, and most are malignant. Only nine cases have been adequately documented in the English-language literature, and there are no reports detailing the fine needle aspiration (FNA) cytologic characteristics.

CASE: A 32-year-old female presented with a left-sided nodular thyroid mass with left cervical lymphadenopathy. FNA cytology of the thyroid and lymph nodes was done. The cytologic and immunocytochemical features were that of a small round cell tumor with neuroepithelial (NE) differentiation, metastasizing to the cervical nodes. Microscopic study of the thyroidectomy specimen showed a tumor showing an NE pattern with occasional islands of squamous and cuboidal epithelium, leading to a diagnosis of malignant teratoma.

CONCLUSION: Knowledge of FNA cytologic features of rare but highly malignant lesions like thyroid teratomas allow early recognition so that suitable and possibly aggressive treatment protocols can be adopted in the hope of prolonging survival.
Malignant rhabdoid tumour of the kidney: report of a case showing focal glomeruloid differentiation

Jayaram G, Looi LM

Malays J Pathol, 1994 Jun;16(1):83-7.
PMID: 16329582

A five-month-old male baby presented with an abdominal mass which was found on computerised tomography (CT) to be involving the left kidney. Nephrectomy and histopathological study showed morphological featues of a malignant rhabdoid tumour. The tumour cells stained strongly for cytokeratin and epithelial membrane antigen and less intensely for vimentin. Electron microscopy revealed concentric whorled arrays of intermediate filaments within the tumour cell cytoplasm. The child was put on post-operative chemotherapy and radiotherapy but developed bilateral lung metastases and died three months after surgery.
Fulltext MRI appearances of peritoneal mesothelioma--a case report

Hashim S, Abdullah BJJ, Jayaram G

Med J Malaysia, 1999 Sep;54(3):358-60.
PMID: 11045063

A rare case of diffuse malignant peritoneal mesothelioma in a 71 year-old Malay man with no previous history of asbestos or radiation exposure is described. The clinical manifestation was a large abdominal mass. At laparotomy he was found to be in the advanced stage of the disease. The tumour was not resectable and patient was sent home. He gradually deteriorated and died three months after diagnosis was made. The magnetic resonance imaging (MRI) features of peritoneal mesothelioma which has not been previously reported are described.
Fulltext Localised nodular pulmonary amyloidosis in a patient with sicca syndrome

Srinivas P, Liam CK, Jayaram G

Med J Malaysia, 2000 Sep;55(3):385-7.
PMID: 11200724

A 52 year old Chinese woman with a 25 year history of sicca syndrome (primary Sjogrens syndrome) was investigated for 3 episodes of haemoptysis. Clinical examination was unremarkable except for the presence of dry eyes and xerostomia. Computed tomography of the chest revealed a lobulated mass in the posterior basal segment of the left lower lobe. Histopathological examination of this resected nodule confirmed the diagnosis of nodular amyloidosis. The normal radiolabelled serum amyloid P component scintigraphy and the absence of monoclonal plasma cell dyscrasia in the bone marrow strongly support the diagnosis of localised nodular pulmonary AL amyloidosis in this patient. Nodular pulmonary amyloidosis can be associated with sicca syndrome and often simulates bronchogenic carcinoma, bronchiectasis or pulmonary tuberculosis.
Leiomyosarcoma of the breast: report of a case with fine needle aspiration cytologic, histologic and immunohistochemical features

Jayaram G, Jayalakshmi P, Yip CH

Acta Cytol., 2005 Nov-Dec;49(6):656-60.
PMID: 16450908

BACKGROUND: Leiomyosarcoma of the breast is a rare neoplasm. We present a case of primary leiomyosarcoma of the breast in a middle-aged female in whom fine needle aspiration cytologic features suggested sarcoma.

CASE: A 55-year-old female presented with a rapidly growing breast lump of 1 month's duration. On examination, an ulcerating, 12 x 10 cm tumor was seen involving the lower medial and lateral quadrants of the right breast. Fine needle aspiration cytology showed variably sized, dissociated and loosely clustered polygonal, plump and spindle cells with pale blue cytoplasm and vesicular nuclei that were round, oval or irregular. Occasional giant forms and nucleolated and mitotic cells were present. A single cluster of benign ductal cells was seen. The tumor cells did not express immunocytologic reactivity to estrogen receptor protein. A cytologic diagnosis of sarcoma was given with differential diagnoses of metaplastic carcinoma and malignant phyllodes tumor. Histologic study established the diagnosis of leiomyosarcoma. Leiomyosarcoma of the breast shows fine needle aspiration cytologic features of sarcoma, but specific tumor typing may not be possible, especially when the cytologic material is inadequate for ancillary staining required to distinguish leiomyosarcoma from metaplastic carcinoma and malignant phyllodes tumor.
Interdigitating dendritic reticulum cell sarcoma: cytologic, histologic and immunocytochemical features

Jayaram G, Mun KS, Elsayed EM, Sangkar JV

Diagn Cytopathol, 2005 Jul;33(1):43-8.
PMID: 15945093

Tumors of dendritic reticulum cells are rare neoplasms that exhibit significant morphologic overlap with other malignancies. Fine-needle aspiration cytologic appearances of this neoplasm are not well understood. A 33-yr-old woman presented with a rapidly growing nodular mass in the right upper cervical region and right-sided ptosis. Fine-needle aspiration cytology of the mass showed dissociated as well as clustered, large, polygonal cells that showed high nuclear-cytoplasmic ratio. Nuclei were round, oval, or irregular in shape. Large and small blastoid forms with prominent nucleoli and chromatin clumping as well as binucleated cells and cells with lobulated nuclei were seen. Numerous mitoses were observed. The tumor cells expressed focal immunocytochemical reactivity to CD45 and CD68, but were negative for CD2, CD3, CD4, CD8, CD20, CD30, CD45RO, epithelial membrane antigen (EMA), cytokeratin, and HMB45. Histologic sections of the biopsy from the growth showed nodal tissue effaced by a tumor composed of large, pleomorphic neoplastic cells with some binucleate and multinucleate forms resembling Reed-Sternberg cells. The intervening stroma contained numerous small lymphocytes. Tumor cells expressed vimentin, S-100 protein, CD68, and MAC387, but were negative for LCA, CD1a, CD3, CD15, CD20, CD21, CD23, CD30, CD35, carcino-embryonic antigen, HMB45, cytokeratin AE1/3, EMA, myeloperoxidase, lysozyme, smooth-muscle actin, and desmin. The combined histologic and immunohistologic features suggested a histiocytic/dendritic reticulum cell neoplasm and a diagnosis of interdigitating dendritic reticulum cell sarcoma was made.
Four quadrant fine needle aspiration cytology of non-palpable benign proliferative breast lesions

Jayaram G, Lamba S, Kakar A

Malays J Pathol, 1993 Dec;15(2):131-6.
PMID: 8065174

Seventy-eight symptomatic females without palpable breast lumps were subjected to bilateral four quadrant fine needle aspiration cytology. Cytological evidence of an epithelial proliferative lesion was seen in 44 of these cases. Based on the cytological evidence of proliferation, the site for open biopsy was determined. Histopathological study of the breast biopsies in these patients showed proliferative disease without atypia (PDWA) in 40 cases, atypical ductal hyperplasia (ADH) in two, atypical lobular hyperplasia (ALH) in one and ADH with ALH in one case. Cytology was thus useful in establishing the presence of proliferative activity, commenting on the extent of proliferation, and thereby roughly mapping out the area of the breast most suitable for biopsy. On cytological grounds, it was not possible to distinguish the atypical hyperplastic lesions from the proliferative diseases without atypia.

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