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  1. Cytologic features and differential diagnosis in chondroma of the breast: a case report
    Sivakumar S, Kaur G
    Acta Cytol., 2009 May-Jun;53(3):303-5.
    PMID: 19534271 DOI: 10.1159/000325312
    BACKGROUND: Extraskeletal (soft tissue) chondromas are rare neoplasms. They are seen most frequently in the soft tissues of hands and feet. A chondroma occurring in the breast is exceedingly uncommon. We present a case of pure chondroma of the breast in a young woman in whom fine needle aspiration (FNA) cytologic features suggested a cartilaginous neoplasm.

    CASE: A 28-year-old woman presented with a mobile lump in the left breast. Mammography showed a high-density nodule without microcalcifications. A clinical diagnosis of fibroadenoma was made. A differential diagnosis was obtained on FNA. Excisional biopsy of the lump showed the histopathologic features of chondroma. There was no recurrence or appearance of new lesion during 13 months of follow-up.

    CONCLUSION: Chondroma of the breast shows FNA cytologic features of cartilaginous tumor, but specific tumor typing may not be possible. This case highlights the difficulties that may arise in FNA diagnosis of cartilaginous tumor especially when it occurs at an unusual site. Awareness of the cytologic features combined with clinical and radiologic findings should guide the cytopathologist to make correct diagnosis of this neoplasm.
  2. Pilomatrixoma as a diagnostic pitfall in fine needle aspiration cytology: a case report
    Sivakumar S
    Acta Cytol., 2007 Jul-Aug;51(4):583-5.
    PMID: 17718128 DOI: 10.1159/000325801
    BACKGROUND: Pilomatrixoma (pilomatrixoma, calcifying epithelioma of Malherbe) is a relatively uncommon, benign neoplasm arising from the skin adnexa. The tumor can cause diagnostic difficulty not only for the clinician but also for the cytologist.

    CASE: A 62-year-old woman presented with a right submandibular swelling of 4 months' duration. The clinical findings were highly suspicious for malignancy. A fine needle aspiration biopsy was performed. Three preliminary differential diagnoses were offered: mucoepidermoid carcinoma of the submandibular salivary gland, squamous cell carcinomatous deposit in a submandibular lymph node and calcifying odontogenic tumor. Computed tomography demonstrated no bony lesion. No primary site of squamous cell carcinoma could be identified. An excisional biopsy of the swelling was performed, and the histologic diagnosis of pilomatrixoma was made.

    CONCLUSION: The cytologic presentation of pilomatrixoma of the right submandibular region can masquerade as that of a malignant tumor, in this case mucoepidermoid carcinoma, squamous cell carcinoma or odontogenic tumor. This case delineates the cytomorphologic features of pilomatrixoma that may mimic carcinoma.
  3. Role of fine needle aspiration cytology in detection of microfilariae: report of 2 cases
    Sivakumar S
    Acta Cytol., 2007 Sep-Oct;51(5):803-6.
    PMID: 17910352 DOI: 10.1159/000325846
    BACKGROUND: Filariasis is a major public health problem in developing countries, and the diagnosis is conventionally made by demonstrating microfilariae in the peripheral blood smear. However, microfilariae have been incidentally detected in fine needle aspirates of various lesions in clinically unsuspected cases of filariasis with absence of microfilariae in the peripheral blood.

    CASES: In case 1, a 21-year-old woman presented with multiple left axillary lymphadenopathy of 3 months' duration. In case 2, a 32-year-old woman presented with a thyroid nodule of 7 months' duration. Fine needle aspiration smears from both cases showed sheathed microfilariae of Wuchereria bancrofti. In both cases, microfilariae could not be demonstrated in the peripheral blood smears and the blood eosinophil counts were within normal limits. The histopathologic examination showed neither microfilariae nor adult worm.

    CONCLUSION: Although microfilariae in cytologic material are considered incidental findings, these cases illustrate the value of routine fine needle aspiration cytology in the detection of asymptomatic and clinically unsuspected cases of bancroftian filariasis. Absence of microfilariae in the peripheral blood does not exdude filarial infection.
  4. 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.
  5. Carcinosarcoma of the palate: report of a case with a diagnosis of sarcomatoid metastasis by fine needle aspiration cytology
    Jayaram G, Elsayed EM
    Acta Cytol., 2005 Sep-Oct;49(5):520-4.
    PMID: 16334029
    BACKGROUND: Carcinosarcoma (sarcomatoid carcinoma) is a rare tumor with a high predilection for the aerodigestive tract. Cytologic diagnosis of metastatic carcinosarcoma has been reported in very few cases.

    CASE: An 84-year-old woman presented with a 2-cm-diameter, right cervical lymph node that was referred for fine needle aspiration cytology (FNAC). She had received radiotherapy for a palatal squamous cell carcinoma 2 years earlier. The FNAC smears had a sarcomatoid appearance. Repeat fine needle aspiration was performed, with cytologic and immunocytochemical staining. Careful consideration of the cytologic and immunophenotypic features led to an impression of carcinosarcoma. Histologic sections of the palatal biopsy that had been previously diagnosed as squamous cell carcinoma were reviewed, and a final diagnosis of carcinosarcoma was established.

    CONCLUSION: Metastasis of rare lesions, such as carcinosarcoma may be confusing and difficult to diagnose on FNAC, especially when the cytologic sample shows a predominantly sarcomatoid component. The difficulty is compounded when the sarcomatoid component happens to have been overlooked on the initial histologic assessment. With representative cytologic sampling, immunocytochemical staining and review of the histologic material, the correct diagnosis was achieved in this case.
  6. Cytologic evaluation of prognostic markers in breast carcinoma
    Jayaram G, Elsayed EM
    Acta Cytol., 2005 Nov-Dec;49(6):605-10.
    PMID: 16450899
    To type breast carcinomaon on fine needle aspiration cytology (FNAC) material and correlate the results with histologic typing, to grade breast carcinoma on FNAC material and correlate the findings with Bloom-Richardson histologic grading, and to determine the estrogen receptor (ER) status in cases of breast carcinoma by immunocytochemical (ICC) staining of FNA cytologic material and correlate the findings with ER status, as determined by immunohistochemical (IHC) staining of tissue sections.

    STUDY DESIGN: Seventy-seven cases of breast carcinoma diagnosed on FNAC formed the basis of this study. Typing was done in all cases on the basis of cytologic features and grading in 62. (Fifteen cases were special types of breast carcinoma). In all cases, ER status was determined by immunostaining of cytologic smears. Results of tumor typing, grading and ER status on cytologic material were compared with the results of histologic typing, grading and immunostaining of histologic material obtained from mastectomy or wide excision specimens.

    RESULTS: Tumor typing was accurate in 73 of 77 cases (94.8%). Fifteen of 18 cases that were cytologically grade 3 were confirmed on histology, while 3 proved to be grade 2. Of 40 cytologic grade 2 cases, 26 were confirmed on histology, while 14 cases were grade 3. Three of 4 cytologically grade 1 cases were confirmed on histology while 1 was grade 2. The overall accuracy for cytologic grading was 71% (44 of 62 cases). Thirty-seven of 40 ER-positive cases (92.5%) were labeled ER positive on ICC. One case was ER negative on cytology, while in 2 cases the cellularity of the cytologic smear was insufficient to assess ER expression. Thirty-seven cases were negativefor ER on IHC. Nine of these showed ER positivity on ICC, 26 were negative, and 2 had cellularity that was inadequate for assessment of ER. Sensitivity and specificity rates for ER detection on ICC were 97.4% and 74.3%, respectively.

    CONCLUSION: Tumor typing, grading and evaluation of ER status on FNA C material in breast carcinomas are simple, quick and moderately reliable techniques that compare and correlate favorably with histologic typing, grading and ER status on IHC.
  7. 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.
  8. Intraventricular squamous papillary craniopharyngioma: report of a case with intraoperative imprint cytology
    Madhavan M, P JG, Abdullah Jafri J, Idris Z
    Acta Cytol., 2005 Jul-Aug;49(4):431-4.
    PMID: 16124175
    BACKGROUND: Squamous papillary craniopharyngioma is a distinct entity, and its cytologic features may be misleading. Because of the rarity of this tumor, this case is being reported with a note on the cytologic features.

    CASE: A 56-year-old Malay man who had 1-month history of generalized lethargy was admitted for altered sensorium. On examination, he was found to have neck stiffness, bilateral papilledema and generalized atrophy of muscles, with reduced power in all limbs. Magnetic resonance imaging of the brain showed a solid mass in the third ventricle causing obstructive hydrocephalus. Intraoperative cytology of the mass diagnosed intraventricular meningioma. However, the final histopathologic examination revealed squamous papillary craniopharyngioma.

    CONCLUSION: Craniopharyngioma, squamous papillary type, is a rare entity and usually occurs in adults as an intraventricular solid tumor. Awareness of this entity will aid in arriving at the correct cytologic diagnosis.
  9. 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.
  10. Fine needle aspiration cytology of lymph nodes in HIV-infected individuals
    Jayaram G, Chew MT
    Acta Cytol., 2000 Nov-Dec;44(6):960-6.
    PMID: 11127753
    OBJECTIVE: To assess the role of fine needle aspiration cytology (FNAC) in lymphadenopathy in human immunodeficiency virus-infected individuals (HIVII).

    STUDY DESIGN: Thirty-nine HIVII presenting with lymphadenopathy at University Hospital, Kuala Lumpur, were subjected to FNAC. Cytologic smears were routinely stained with May-Grünwald-Giemsa stain. Special stains and immunostains were used when necessary.

    RESULTS: In nine cases, the cytologic appearance was compatible with HIV type A and in one case with HIV type C lymphadenopathy. In 21 cases, acid-fast bacilli (AFB) were demonstrated in the cytologic smears, enabling a diagnosis of mycobacterial lymphadenitis. In one of these cases there was a concomitant infection with Penicillium marneffei that was overlooked on initial cytologic examination. The cause of granulomatous lymphadenitis could not be ascertained in one case, where neither AFB nor any other organisms were demonstrable. Two cases of histoplasma and one of cryptococcal lymphadenitis were diagnosed, as was one high grade non-Hodgkin's lymphoma that could be immunophenotyped on cytologic material. In three cases the aspirates were inadequate for a cytologic diagnosis.

    CONCLUSION: Lymph node FNAC is a valuable investigative modality in HIVII. Most opportunistic infections (bacterial and fungal) can be correctly identified, and high grade lymphoma can be diagnosed and phenotyped.
  11. Cytologic appearances in invasive lobular carcinoma of the breast. A study of 21 cases
    Jayaram G, Swain M, Chew MT, Yip CH
    Acta Cytol., 2000 Mar-Apr;44(2):169-74.
    PMID: 10740602
    OBJECTIVE: To examine the fine needle aspiration cytologic features of invasive lobular carcinoma of breast and to discuss problems that may occur in cytodiagnosis.

    STUDY DESIGN: Fine needle aspiration cytologic smears from 21 cases of invasive lobular carcinoma (ILC) of breast were subjected to detailed cytomorphologic analysis. Features studied included pattern of cells, size of cells, nuclear placement, pleomorphism, presence of intracytoplasmic lumina (ICL) and signet ring cells.

    RESULTS: Cellularity was generally moderate or high, and the pattern was predominantly or partly dissociated in 86% of cases. Rosettelike pattern was discerned in alveolar-type ILC. Cell size was usually small or intermediate, with nuclei placed eccentrically in most cases. ICLs with or without signet ring cells were present in 12 cases (57%).

    CONCLUSION: A cytologic picture consisting of predominantly dissociated small or intermediate-sized tumor cells with eccentric nuclei, with some of the cells showing ICLs, is highly suggestive of ILC. Indian file pattern, another characteristic feature of ILC, is, however, focal and inconsistent. Variant patterns of ILC may show other cytologic features, such as rosettelike pattern (alveolar variant of ILC) or large cell pattern (pleomorphic variant of ILC) and may consequently be difficult to categorize on cytologic smears.
  12. Cytology of Ki-1-positive anaplastic large cell lymphoma. A report of two cases
    Jayaram G, Abdul Rahman N
    Acta Cytol., 1997 Jul-Aug;41(4 Suppl):1253-60.
    PMID: 9990253
    Ki-1-positive anaplastic large cell lymphoma (Ki-1 ALCL), one of the more recently described pleomorphic types of lymphoma, affects mostly children and adolescents and is sometimes mistaken for carcinoma or sarcoma.
  13. Cystic lesion of the parotid gland with squamous metaplasia mistaken for squamous cell carcinoma. A case report
    Jayaram G, Pathmanathan R, Khanijow V
    Acta Cytol., 1998 Nov-Dec;42(6):1468-72.
    PMID: 9850664
    BACKGROUND: The diverse range of diseases that affect the salivary glands may lead to problems and pitfalls in cyto-diagnosis. While false negative diagnosis of cystic salivary gland tumors is well known, false positive cytodiagnosis in nonneoplastic salivary cysts is less well documented.

    CASE: An 85-year-old female presented with a painless left parotid gland swelling of three months' duration. Fine needle aspiration cytology yielded fluid, smears of which showed keratinizing squamous cells with nuclear atypia leading to a cytologic diagnosis of cystic squamous cell carcinoma. A total radical parotidectomy followed. Histopathologic study showed cystic dilatation of many of the salivary ducts, which were lined with metaplastic squamous epithelium that showed atypia. There was no evidence of squamous cell carcinoma.

    CONCLUSION: Squamous metaplasia is known to occur in benign salivary gland lesions, such as pleomorphic adenoma and Warthin's tumors, as well as in salivary duct cysts and necrotizing sialometaplasia. However, atypical squamous metaplasia of salivary duct cysts mimicking squamous cell carcinoma on cytology is unusual.
  14. Epidemiology of cervical carcinoma in Brunei Darussalam. Analysis of data on 27,208 women screened with cytologic examinations
    Affandi MZ, Dun T, Mantuano V, Sidhu R, Lumplugh C, Telisinghe PU
    Acta Cytol., 1993 Mar-Apr;37(2):175-80.
    PMID: 8465637
    During the five-year period from January 1985 to December 1989 a total of 27,208 women, representing 44.0% of the total female population over age 15 years in Brunei Darussalam, underwent a cytologic examination. The majority of them were Malays (62.32%), followed by Chinese (22.23%), while the remainder were the expatriate population living in the country. High grade squamous intraepithelial lesion (moderate dysplasia) was detected in 88 women (3.3/1,000), high grade squamous intraepithelial lesion (carcinoma in situ) was seen in 32 women (1.22/1,000), and invasive carcinoma was found in 43 women (1.37/1,000). The overall detection rate for cervical cancer was 2.79/1,000 women in the population screened. In Brunei Darussalam Malay women marry at an early age, 44% by the age of 19 years, leading to sexual contact before the age of 20. However, the incidence of cervical cancer is low among them. This could be because they belong to the Orthodox Muslim Society, in which promiscuity is not permitted. Hence, multiple sex partners could be an important factor in the etiology of cervical cancer, confirming the current trend of thought that cervical cancer is a sexually transmitted disease. A comparison of the epidemiologic risk factors among the various races living in Brunei Darussalam is made.
  15. Diagnostic Value of the EZH2 Immunomarker in Malignant Effusion Cytology
    Ang PP, Tan GC, Karim N, Wong YP
    Acta Cytol., 2020;64(3):248-255.
    PMID: 31352449 DOI: 10.1159/000501406
    BACKGROUND: Differentiating reactive mesothelial cells from metastatic carcinoma in effusion cytology is a challenging task. The application of at least 4 monoclonal antibodies including 2 epithelial markers (Ber-EP4, MOC-31, CEA, or B72.3) and 2 mesothelial markers (calretinin, WT-1, CK5/6, or HBME-1) are often useful in this distinction; however, it is not readily available in many resource-limited developing countries. Aberrant immunoexpression of enhancer of zeste homolog 2 (EZH2), a transcriptional repressor involved in cancer progression, is observed widely in various malignancy. In this study, we evaluate the diagnostic value of EZH2 as a single reliable immunomarker for malignancy in effusion samples.

    METHODS: A total of 108 pleural, peritoneal, and pericardial effusions/washings diagnosed as unequivocally reactive (n = 41) and metastatic carcinoma (n = 67) by cytomorphology over 18 months were reviewed. Among the metastatic carcinoma cases, 54 were adenocarcinoma and others were squamous cell carcinoma (n = 1), carcinosarcoma (n = 1), and carcinoma of undefined histological subtypes (n = 11). Cell block sections were immunostained by EZH2 (Cell Marque, USA). The percentages of EZH2-immunolabeled cells over the total cells of interest were calculated. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off score to define EZH2 immunopositivity.

    RESULTS: A threshold of 8% EZH2-immunolabeled cells allows distinction between malignant and reactive mesothelial cells, with 95.5% sensitivity, 100% specificity, 100% positive predictive value, and 93.2% negative predictive value (p < 0.0001). The area under the curve was 0.988.

    CONCLUSION: EZH2 is a promising diagnostic biomarker for malignancy in effusion cytology which is inexpensive yet trustworthy and could potentially be used routinely in countries under considerable economic constraints.

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