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OBJECTIVE Rapid on-site evaluation (ROSE) is a fine needle aspiration (FNA) technique for ensuring sampling adequacy and triaging samples. The Milan system for reporting salivary gland cytopathology (MSRSGC) is a standardised reporting system which aims to improve risk stratification. There is scant literature on the diagnostic value and agreement of MSRSGC on ROSE with final cytological diagnosis in salivary gland FNAs. We aimed to assess the concordance of MSRSCG categorisation and diagnosis on ROSE with final cytological and histological diagnosis. METHODS This prospective study included consecutive salivary gland FNAs for which ROSE was performed over a six-month period. MSRSGC category and diagnosis on ROSE were compared with the final cytological diagnosis and MSRSGC category, and histopathological diagnosis, where available. RESULTS Sixty salivary gland aspirates were included. The adequacy rate with ROSE was 100%. Using the MSRSGC classification during ROSE, 26 (43.2%) samples were categorised as benign neoplasm, 21 (35%) as malignant neoplasm, 9 (15%) as non-neoplastic, and one each (1.7%) belonged to the remaining four categories. MSRSGC categorisation on ROSE concurred with final the cytological diagnosis in 58/60 cases (96.7%). Discrepancies in MSRSGC categories on ROSE included one atypia of undetermined significance with final report as non-neoplastic, and one non-diagnostic as suspicious for malignancy. Good correlation of MSRSGC categories on ROSE with final histopathological diagnosis (88.9% concordance) was also noted. CONCLUSIONS MSRSGC on ROSE shows good concordance with final cytology and histopathology diagnosis, indicating that categorisation according to MSRSGC has utility in ensuring that adequate material is obtained and triaged appropriately for the diagnosis of salivary gland aspirates.

Objective Langerhans cell histiocytosis (LCH) is a rare disease affecting predominantly children and young adults but can be found in any age group. Diagnosis of LCH is often difficult and can be delayed because of its rarity. The present study highlights the cytomorphological features in a large cohort of cases. An accurate cytological diagnosis may avoid unnecessary biopsy and guide appropriate management. Method Fourty seven (47) cases of LCH diagnosed on cytological material & fine-needle aspiration (FNA) over a period of 14 years (2003-2016) were retrieved from the archives. The cytological smears were evaluated and microscopic findings collected by semi-quantitative assessment done by two different pathologists RESULT: The age at the diagnosis of the patients ranged from 9 months to 28 years. The majority of cases were in the age group of 0-5 years. The most common site was head and neck region, which included cervical lymphadenopathy and scalp swelling. Two cases were diagnosed each from inguinal lymph node and bronchio-alveolar lavage (BAL). Cytological smears in the majority of the cases were moderate to highly cellular (58%) and showing abundant Langerhans cell in (72%) of cases. Areas of necrosis were seen in 38%, while 78% of cases showed giant cells. The majority of cases showed mild eosinophilia (61%), sparse lymphocytosis (83%) and mild neutrophilic infiltration (64%). There were 1-2 mitoses per 10 high power field in 12 cases (25.5%). No abnormal mitoses were identified. Conclusion The presence of cells with features of Langerhans cells associated with the expression of selected immunohistochemical markers allow the diagnosis of LCH on cytological samples, sparing more invasive procedure as a biopsy.

Objective Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is an aggressive extranodal lymphoma of NK-cell or T-cell lineage. Its clinical features overlap with those of several sinonasal mass lesions. While the histopathological features are well described, diagnosis is often difficult, owing to presence of extensive coagulative necrosis, so that repeated biopsies may sometimes be necessary for correct diagnosis. Literature on cytological findings of ENKTL is limited. Methods Cytomorphological features of cases of histologically confirmed ENKTL having corresponding cytology samples were reviewed retrospectively, to identify distinctive features that could possibly suggest this entity. Results Aspirates from five patients were studied: four from cervical nodes, one from cheek swelling and one from pleural fluid. Two aspirates were reported as positive for malignancy, two as atypical lymphoid proliferation and one was non-diagnostic. Pleural fluid was reported as malignant, favouring a diagnosis of carcinoma. On cytology, aspirates showed medium to large cells with folded, indented nuclei and abundant pale cytoplasm, some with tongue-like cytoplasmic protrusions. A distinctive feature was presence of large loose clusters of tumour cells with arborising capillaries running through them. Interestingly, necrosis was consistently absent. Subsequent biopsies from palate (three cases) and nasal masses (two cases) confirmed the diagnosis of ENKTL. Conclusions Suspicion of ENKTL on cytology is crucial for timely diagnosis to avoid diagnostic delay, especially when only highly necrotic biopsy samples are available. Awareness of distinctive cytomorphological features is required to make fine needle aspiration an effective diagnostic tool for initial diagnosis and for evaluation of possible recurrences.

Fine-needle aspiration cytology (FNAC) is an effective tool for early and quick diagnosis of malignant and metastatic liver masses. However, diagnosing a benign liver tumor on cytology is a challenging task as they are rarely assessed on cytology and also due to the limitations of the procedure. Mesenchymal hamartoma is an uncommon benign pediatric liver tumor and difficult to diagnose on cytology. We describe here a case of a child who presented with a huge liver mass and clinical suspicion of hepatoblastoma. The child underwent blind FNA, and was diagnosed as mesenchymal hamartoma based on the cytological features. A biopsy was performed subsequently which confirmed the same and then he underwent surgical resection of the tumor. The patient had an uneventful recovery and is disease free on follow up.

Giant cell tumor of the larynx is an uncommon entity with only 44 cases reported in the literature. These tumors occur most commonly in the epiphysis of the long bones of female patients in third decade. Here in we report a case of 23 years old male patient who presented with an anterior neck swelling since past 4 months. Ultrasound and computed tomography of neck revealed a heterogenously enhancing lesion involving posteroinferior half of right thyroid cartilage with extension into the extra laryngeal strap muscle and intralaryngeal right true vocal cord and false vocal cord. The findings were suggestive of a neoplastic cartilagenous lesion. A fine needle aspiration of the right anterior neck mass was performed which showed many mononuclear cells along with multinucleated osteoclast type giant cells. No thyroid follicular cells or inflammatory cells were seen. A diagnosis of giant cell tumor of the thyroid cartilage was rendered on cytology. A biopsy was subsequently performed for the patient which confirmed the same. Hence, although giant cell tumor of the larynx is a rare entity, with very few cases reported in the literature, these tumors should be included in the differential diagnosis of giant cell lesions of the neck and aspiration cytology can offer an accurate and quick diagnosis in such cases.

Solitary fibrous tumor (SFT) is a fibroblastic tumor of the pleura, and subcutaneous and deep soft tissues of the extremities, abdomen, pelvis, and retroperitoneum. In the head and neck region, the sinonasal tract and soft tissues of the orbit are involved most frequently. However, the lacrimal sac is an extremely unusual location for this tumor, with occasional case reports in literature. Being superficially located and palpable, lacrimal sac masses are easily amenable to FNAC. Despite cytological features of SFT being well-documented, they are often underdiagnosed on FNAC. Immunocytochemistry for STAT6 is a sensitive and specific marker that can aid in accurate diagnosis, as is required for planning appropriate management. We describe the case of a 45-year-old lady who presented with a mass at the medial canthus of the right eye, and was diagnosed as SFT on FNAC, based on cytomorphological features and immunopositivity for STAT6. The diagnosis was subsequently confirmed on histological examination.

OBJECTIVE Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a recently described, indolent thyroid tumor, with well-defined histopathological diagnostic criteria. Cytology features are not well documented. We reviewed cytology of histologically proven cases of NIFTP and some of its common differentials to look for salient diagnostic features. METHODS Cases reported on histopathology as follicular variant of papillary thyroid carcinoma (FVPTC), or NIFTP between July 2015 and April 2017 having available cytology smears were retrieved and reclassified as NIFTP, FVPTC, and classical papillary thyroid carcinoma with predominant follicular pattern (PTC-FP). Cytological features were assessed, classified as per The Bethesda System for Reporting Cytopathology and compared. RESULTS There were 23 NIFTP cases, 18 FVPTC and 8 PTC-FP. A microfollicle-predominant pattern was seen in all. Nuclear score was 2 in most NIFTP cases (61%). Pseudoinclusions were absent. NIFTP showed features of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (III) in 61%, follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) (IV) in 35% and suspicious for malignancy (SFM) (V) in 4%. Most of the FVPTCs were also called FN/SFN (IV) (56%) or AUS/FLUS (III) (22%). Nuclear features did not statistically differ from NIFTP. PTC-FP showed high-grade cytology in 75%, and higher nuclear score (3 in 75%) in contrast to NIFTP (P = .003). CONCLUSION NIFTP and FVPTC show a similar distribution among the Bethesda categories hence precluding conclusive distinction on cytology. PTC-FP, in contrast, was found to have a statistically significant higher nuclear score and more commonly showed malignant cytology.

AimsThe 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) recommends subclassification of atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) into six subcategories. The present study evaluates the risk of malignancy (ROM) and risk of neoplasm (RON) among these.MethodsAll thyroid aspirates reported as AUS/FLUS over a 4.5-year period, with available histology, were reviewed and subclassified as per TBSRTC. ROM and RON were calculated and compared.ResultsOf 2554 thyroid aspirates, 281 (11.0%) were AUS/FLUS. Eighty-one with available histology were evaluated. ROM was 51.8%. Cytologic and architectural atypia (AUS-C&A) was the most prevalent (62.9%), followed by Hürthle cell type (19.6%), AUS-A (11.1%), AUS-not otherwise specified (NOS) (7.4%), cytologic atypia (AUS-C) (4.9%) and atypical lymphoid cells (1.2%). Papillary thyroid carcinoma (PTC) and adenomatous goitre (AG) were the most common histological diagnoses (27% each). On histology, AUS-C had 2/4 PTC and 2/4 AG on histology. AUS-A had 4/9 follicular neoplasm (FN) and 2/9 non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) while AUS C&A had 18/51 PTC, 13/51 AG, 11/51 NIFTP and 5/51 FN. ROM and RON were similar across subcategories, ROM was the highest for AUS-C&A (58.8%), AUS-C (50%) and AUS-NOS (50%). NIFTP reclassification as non-malignant reduced ROM to 35.8% (absolute reduction of 16% and a relative decrease of 31%) with the greatest relative decrease seen in AUS-A (50%), followed by AUS-C&A (37%), and none in others.ConclusionsAUS/FLUS subcategorisation helped to indicate risk for the more likely neoplasm, whether PTC or FN. ROM was the highest for cases with cytological atypia but did not differ significantly across different subcategories. NIFTP changed the ROM of AUS-A and AUS-C&A, since both NIFTP and FN have microfollicles.

Objective Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is essential in patients of advanced non-small-cell lung cancer to determine eligibility for immunotherapy. PD-L1 IHC assays have been clinically validated only on formalin-fixed paraffin-embedded tissue; however, lung cancer is frequently diagnosed on cytology. PD-L1 immunocytochemistry (ICC) has shown high concordance of immunoexpression between cytology samples and paired small biopsies. Feasibility of liquid-based cytology (LBC) smears for PD-L1 ICC has not been analysed previously. Methods PD-L1 ICC and IHC (clone SP263) were performed on paired LBC smears and small biopsies, respectively, in patients with advanced non-small-cell lung cancer. Cases with fewer than 100 viable tumour cells on LBC smear/biopsy were excluded from analysis. PD-L1 was interpreted positive when 25% or more tumour cells showed membranous and/or cytoplasmic protein expression of any intensity greater than background staining. Results A total of 26 patients, harbouring adenocarcinomas (50%) and squamous cell carcinomas (50%), had available bronchial brushings/washings processed as LBC smears and concurrently obtained endobronchial biopsies. PD-L1 IHC was interpreted positive in 46% (12/26) biopsies. PD-L1 ICC was interpreted positive in 35% (9/26) LBC smears, all of which were IHC-positive. No IHC-negative case was positive on cytology. The overall concordance between LBC smears and small biopsies was 88.4%. Conclusion PD-L1 ICC can be performed on LBC processed smears, with certain challenges in interpretation inherent to LBC smears and their processing methods. Nevertheless, they represent a potential resource for ICC, especially when alternate histology material is not available. Future studies are required to validate the predictive value of PD-L1 ICC on LBC smears.

Background: Conventional transbronchial needle aspiration (c-TBNA) is an underutilized bronchoscopic modality. Endobronchial ultrasound (EBUS) guided-TBNA though efficacious is an expensive modality, facilities of which are available at only limited centers. c-TBNA is cost-effective and has potential for wide utilization especially in resource-limited settings. Rapid on-site evaluation (ROSE) improves the yield of c-TBNA. Materials and Methods: A retrospective review of the bronchoscopy records (May 2012 to July 2014) was performed. The patients who underwent c-TBNA with ROSE were included in the study and their clinical details were extracted. Convex probe EBUS-TBNA was being regularly performed during the study period by the operators performing c-TBNA. Results: c-TBNA with ROSE was performed in 41 patients with mean age of 42.4 (16.2) years. The most frequently sampled node stations (>90% patients) were the subcarinal and lower right paratracheal. Representative samples could be obtained in 33 out of the 41 patients (80.4%). c-TBNA was diagnostic in 32 [tuberculosis (TB)-8, sarcoidosis-9, and malignancy-15] patients out of the 41 patients. The overall diagnostic yield (sensitivity) of c-TBNA with ROSE was 78%. Mean procedure duration was 18.4 (3.1) min and there were no procedural complications. Conclusion: c-TBNA with ROSE is a safe, efficacious, and cost-effective bronchoscopic modality. When it was performed by operators routinely performing EBUS-TBNA, diagnostic yields similar to that of EBUS-TBNA can be obtained. Even at the centers where EBUS facilities are available, c-TBNA should be routinely performed.

Background Poorly differentiated thyroid carcinoma (PDTC) is an uncommon thyroid malignancy with biological behaviour intermediate between well-differentiated and undifferentiated thyroid carcinoma. The cytological diagnosis of PDTC is often difficult as a result of a lack of well-established cytomorphological features and a considerable degree of morphological overlap with other commoner thyroid neoplasms. Objective To review the cytomorphological features of PDTC with the aim of highlighting salient diagnostic morphological features and differential diagnostic problems. Methods Seven cases of histologically proven PDTC with available aspiration cytology smears were reviewed for the presence of distinguishing cytomorphological features. Results The architectural arrangement of tumour cells was the most important diagnostic parameter. Cellular nests, three-dimensional clusters dyscohesive aggregates and singly dispersed cells in the background were present in all cases. A unique ‘garlanded appearance’, owing to the peripheral orientation of nuclei within the tumour cell clusters, was noted (71.4%) along with the presence of basement membrane-like material (71.4%). Transgressing vessels (85.7%) and endothelial wrapping of cell clusters (71.4%) were also noted. Interestingly, most cases lacked necrosis and mitotic activity that are included in the histological diagnostic criteria for PDTC. Conclusion Although PDTC has considerable cytomorphological overlap with well-differentiated thyroid tumours, this present study highlights certain cytomorphological features that may suggest the correct pre-operative diagnosis, important for the appropriate management.

Background Sebaceous carcinomas (SBCs) are aggressive tumors with the potential to cause great morbidity and mortality. Poorly-differentiated tumors may at times pose challenges for the correct diagnosis. p40, a new antibody that targets a short isoform of p63 has been shown as a promising squamous cell marker. In this study, we sought to evaluate cytomorphological features of SBC and p40 expression analysis. Methods A total of 29 previously diagnosed cases of SBCs including fine-needle aspirates and histopathology specimens from various sites were reviewed and studied for p40 expression. p40 nuclear expression was semi-quantitatively assessed. Adequate positive and negative controls of non-small cell lung carcinoma were taken for comparison. Expression pattern of normal sebaceous glands was also analyzed. Results Of the 29 cases, 13 (44.8%) were from the periocular region. The most common extraocular site was parotid gland. Morphologically tumors were categorized into well- and poorly-differentiated varieties based on extent of sebaceous differentiation. p40 positivity was seen in all cases of cytology aspirates and histology sections with similar intensity. No difference in percentage positivity of cells was recorded in well- and poorly-differentiated tumors. Conclusion p40 can be a valuable marker when evaluating tumors with possible sebaceous differentiation. Although p40 expression in SBCs is not as useful for the differential diagnosis that includes poorly-differentiated squamous cell carcinoma, this study, for the first time in the literature, highlights an important observation that p40 can be utilized as a marker for sebaceous lineage. Diagn. Cytopathol. 2015;43:456–461. © 2015 Wiley Periodicals, Inc.

Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. DOG1 is a sensitive and specific immunohistochemical marker for the diagnosis of GIST. To date, no study has reported the utility of DOG1 immunocytochemistry on aspirate smears. Methods: Aspirates with a cytological diagnosis of GIST were retrieved. DOG1 immunocytochemistry was performed on aspirates with adequate material. Results: 23 cases were included (11 primary, 2 recurrent, 10 metastatic). Primary tumors were most frequently located in the stomach; most metastatic tumors were in the liver. Tumor cells were arranged in cohesive clusters with high cellularity. Cells were spindled, had a low N:C ratio, and a moderate amount of cytoplasm, which was elongated and tapering. Characteristic nuclear features included elongated nuclei with blunt or tapering ends, fine chromatin, mild anisonucleosis, and longitudinal grooves. The mitotic count was low, including in metastatic tumors. DOG1 immunopositivity was noted in 57% of the cases examined. Histopathology was available in 5 cases, all diagnosed as GIST. Conclusion: Cytology is a sensitive investigative modality for the preoperative diagnosis and confirmation of metastasis of GISTs. In ambiguous cases, DOG1 immunocytochemistry can serve as a valuable adjunct. Cytologic assessment, however, cannot predict malignant potential of GISTs as even metastatic tumors display bland nuclear features.

Objective: Direct microscopic visualization is the most specific method for detecting intestinal parasites and is commonly achieved by stool examination or mucosal biopsy. However, postfixation, the intestinal biopsy fragment is often curled, and the entire surface of the biopsied mucosa is seldom viewed microscopically. Tissue processing further distorts morphology of the organisms and causes diagnostic difficulties. Examining multiple sections for parasite detection is time-consuming and often requires aid of special stains and/or immunohistochemistry. To overcome these disadvantages, we hypothesized that the fixative in which biopsies are transferred may provide a valid representation of the biopsied mucosal surface and therefore aid in the identification of mucosal surface parasites.Materials and Methods: Formalin in which biopsies were transferred was retained, stored at 4°C and processed with a cytocentrifuge. Totally, 120 consequent duodenal biopsy fixatives were processed in this way and the cytocentrifuged smears visualized after May-Grunwald-Giemsa staining. Findings of these smears were correlated with their corresponding formalin fixed paraffin embedded tissue sections.Results: Cytocentrifuged formalin preparations were found to be representative of the mucosal surface contents. Giardia trophozoites were visualized in 10/120 preparations with distinct morphological characteristics which were seldom appreciable in tissue sections, eliminating the need for special stains. Furthermore, two of the corresponding histology sections did not demonstrate the parasites despite step sections, while in one case few parasites could be identified in the step sections. Conclusions: Cytocentrifuged fixative preparation is a simple and cost-effective technique which can be routinely employed for intestinal parasite characterization.

Background Urine cytology is a highly specific modality for diagnosing high-grade urothelial carcinoma (HGUC), but plagued by low sensitivity and wide inter-observer variability mainly ascribed to the lack of an established template of reporting. The Paris System (TPS) working group proposed such a template at the 2013 International Congress of Cytology, replete with objective criteria for categorising specimens into one of the seven categories: non-diagnostic, negative for HGUC, atypical urothelial cells, suspicious for HGUC, HGUC, low-grade urothelial neoplasm and others (including non-malignant entities). This study was undertaken to determine the impact of TPS criteria in the morphological interpretation of urine samples. Methods A total of 255 voided urine specimens from 97 patients who had follow-up biopsies were re-assessed according to TPS criteria and correlated with the final histological diagnosis. Results Sixty-three patients were diagnosed with HGUC, and 34 had low-grade papillary UC on biopsy. Earlier samples from 40 (41.2%) patients were categorised as merely “atypical” wheereas the “positive for malignancy” category was assigned to 33 (34%) patients. After re-evaluation of the same cases using TPS criteria, cytological features in 44 (69.8%) out of 63 HGUC patients were correctly recognised as HGUC and samples from additional seven patients were re-categorised as suspicious for HGUC (total 81%). The sensitivity of the HGUC category in predicting HGUC was 69.8% which rose to 81% when HGUC was grouped with suspicious for HGUC category. Conclusion The criteria outlined by TPS facilitated the standardisation of urine cytology reporting and significantly increased the sensitivity of diagnosing HGUC.

Background: Rosai-Dorfman disease (RDD) is a rare benign idiopathic histiocytic proliferation. Most commonly reported cases are lymph nodal. Only 30-40% of cases occur in extranodal sites. Although the morphological features of RDD are well documented, there is limited information about the morphometric variations in the histiocytes of this entity. Method: Twenty-two cases of RDD diagnosed on fine-needle aspiration cytology (FNAC) were retrieved from the archives. Both Papanicolaou- and May-Grünwald-Giemsa-stained slides were available for evaluation in all cases. Nuclear area, diameter and histiocyte size were measured taking reactive histiocytes as controls. Results: Among the 22 patients (male/female ratio 3:2; age range 5-55 years, mean 26 years), 3 cases were extranodal and 19 cases were nodal. The nodal sites included cervical, axillary, inguinal and submandibular lymph nodes. The extranodal sites were the retroperitoneum, mediastinum and skin. The most common clinical presentation was enlarged lymph nodes. Cytological features included numerous large benign histiocytes with emperipolesis. All the morphometric parameters were significantly (p < 0.01) higher in RDD histiocytes than in histiocytes in the reactive lymph node. Conclusions: In view of the rarity of the disease and the variable clinical presentation in RDD, accurate diagnosis is necessary. This is the first study to document the morphometric parameters of RDD histiocytes and their comparison with histiocytes in the reactive lymph node.

Objectives: Fine-needle aspiration cytology serves as a rapid and cost-effective tool for the diagnosis of melanoma, especially in the recurrent and metastatic cases. The diagnosis poses a challenge due to the varied morphological patterns. Spindle cell melanoma mimics other sarcomas and carcinomas on morphology. This study highlights the cytomorphological features of spindle cell melanoma and compares them with the conventional epithelioid type. Study Design: Cytology smears of 55 aspirates from 45 diagnosed cases of melanoma from various sites were reviewed. Histopathology correlation was done in spindle and mixed cell tumors. Results: Melanomas with a pure or mixed spindle cell component occurred in 31% of the cases and in a slightly higher age group. These demonstrated prominent cellular cohesion (p < 0.0001), mild to moderate nuclear atypia and inconspicuous to small nucleoli as compared to the epithelioid variant. The presence of melanin pigment was a useful clue to the diagnosis. Most of the cases correlated well with the histomorphology. Conclusion: Spindle cell melanoma is a morphological variant which can be readily misinterpreted due to a lack of classical cytological features of melanoma. Hence, these are vulnerable to be misinterpreted as other neoplasms. An awareness of clinical and cytological features is important to reach the correct diagnosis.

Objective: Microfilaria of Wuchereria bancrofti has been described in many cytological specimens, where typical blood film morphology has been used for evaluation. However, these studies have not documented the morphological variations in microfilaria in cytological smears. In the present study, cytological findings in 32 clinically unsuspected cases of filariasis were reviewed with emphasis on morphological details and image morphometric measurements. Study Design: A retrospective analysis of 32 cases of clinically unsuspected filariasis diagnosed by cytology from April 2001 to March 2011 was carried out. Results: All microfilariae were characterized as W. bancrofti and showed a wide variation in their length (202 to 300 µm) and width (6.2 to 8.4 µm). Terminal and subterminal swellings were seen in one of the cases causing diagnostic confusion with Brugia malayi. Microfilariae were shorter and wider in May-Grünwald-Giemsa stain than in Papanicolaou-stained smears. Conclusions: Natural variations in the size of microfilariae of W. bancrofti are the probable reason for the range of these findings. The overlapping features with microfilaria of B. malayi might be related to subspecies variations in W. bancrofti. Fixation, degeneration and staining procedure also seem to influence the morphological features. This morphometric study highlights the morphological disparities of microfilaria and the differential diagnostic considerations.

S. Kaushal, V. K. Iyer, S. R. Mathur and R. Ray Fine needle aspiration cytology of medullary carcinoma of the thyroid with a focus on rare variants: a review of 78 cases Background: The cytological features of variants of medullary carcinoma of the thyroid (MCT) are sparsely documented in the literature from case reports. Detailed cytomorphological analysis of MCT variants and features helping to distinguish them from usual MCT are presented here. Materials and methods: A total of 78 aspirates with a diagnosis of MCT over a period of 10 years were re-evaluated. Cytomorphological details were reviewed and semiquantitatively analysed. Histology slides were reviewed in 36 cases. Results: Most aspirates showed classical features of dispersed polygonal or plasmacytoid cells with areas of spindling. In 54 aspirates, a definite cytological diagnosis of medullary carcinoma was made, which in 87.1% was based on cytomorphology alone and in 12.9% was based on immunocytochemistry for calcitonin. In 30.1% of aspirates from MCT, a guarded report of tumour was given in the absence of calcitonin immunocytochemistry. Of the 78 cases, nuclear grooves were seen in 5.1%, intranuclear cytoplasmic inclusions in 28.2%, cytoplasmic granularity in 23.1% and bizarre cells with abrupt anisocytosis in 85.9%. A follicular arrangement was seen in 14.1% and was more frequent in the follicular type (one case) and mixed follicular and medullary carcinoma (one case). Melanin production was seen in aspirates from two cases. One case of the giant cell type of MCT was seen, in which background cells showed large pleomorphic nuclei and numerous bizarre tumour giant cells, prompting a differential diagnosis with anaplastic carcinoma. One example each of the small cell type, paraganglioma-like MCT and papillary MCT were seen. Conclusions: MCT has uniform cytological features in the majority of aspirates, including many of the histological variants. Searching for pigment in every aspirate of MCT may be rewarding. The giant cell type of MCT is rare and has to be differentiated from anaplastic carcinoma.

Objective To study the role of cytology and polymerase chain reaction (PCR) for the detection of Pneumocystis carinii pneumonia (PCP) in bronchoalveolar lavage fluid (BALF). Study design In a prospective observational study, a BALF pellet from 55 patients (35 immunosuppressed patients clinically suspicious for PCP and 20 immunocompetent individuals not suspicious for PCP) were subjected to cytology examination as well as PCR for PCP using the major surface glycoprotein gene. Additionally, DNA was extracted from destained cytology slide scrapings from 5 cases each positive for PCR and negative for PCP on BALF, respectively, and was further subjected to PCR. Results Of 35 immunosuppressed patients, 2 were positive on microscopy for PCP, while 5 (including 2 microscopy positive) were positive by PCR from BALF. Four of the 5 positive cases showed predominantly alveolar macrophages, while one showed 40% alveolar macrophages, 30% lymphocytes and 20% neutrophils upon cellular analysis of BALF. One case had coinfection with Cryptococcus. Destained smear scrapings of PCR-positive slides (n = 5) were all successfully amplified for PCP major surface glycoprotein PCR after DNA extraction, while control slides (n = 5) did not show amplification. Conclusion BALF is considered the sample of choice for the diagnosis of PCP. In our study, cases with PCP showed mainly alveolar macrophages on BALF examination by cytology and no or mild inflammatory cells. Thus, inflammatory cell population found on cytology may provide direction for PCR. Two-step screening of BALF using cytology followed by PCR from slides is possible and may overcome the limitations of BALF cytology alone for the diagnosis of PCP.

P. Das, V. K. Iyer, S. R. Mathur and R. Ray Anaplastic large cell lymphoma: a critical evaluation of cytomorphological features in seven cases Objective: Anaplastic large cell lymphoma (ALCL) is a rare subtype of non-Hodgkin’s lymphoma that is difficult to diagnose on fine needle aspiration cytology (FNAC). Detailed descriptions about the cytomorphological features of ALCL are few and do not illustrate the various categories of cells, which we have done in this study. Methods: Eight FNAC specimens from seven patients with biopsy-proven ALCL over a period of 6 years were reviewed. Cytomorphological details were analysed and the various cell types identified were enumerated on Papanicolaou and May–Grunwald–Giemsa (MGG)-stained smears. Results: Of the seven cases, five were of conventional type, one of the lymphohistiocytic variant and one of the small cell variant. Aspiration from the conventional type showed a mixed population of lymphoid cells with many plasma cells. The tumour cells were intricately admixed within and distributed as single cells without grouping. Distinct hallmark cells, doughnut cells, embryo cells, tennis racket cells, cells with wreath-like nuclei, Reed–Sternberg-like cells and nondescript cells were seen. Nucleoli were rounded, occasionally tubular in shape. The tumour cells showed abundant blue cytoplasm on MGG stain with a perinuclear hoff. Aspiration from the lymphohistiocytic and small cell variants showed a small number of similar characteristic giant cells. All cases were confirmed as ALK-1 positive. Conclusions: The morphological spectrum of ALCL is wide and it may be misdiagnosed as a metastatic poorly differentiated malignant tumour on FNAC. Identification of unusual giant cells on FNAC helps in establishing a diagnosis on an early lymph node biopsy.

This study examines variation of morphologic features, including emperipolesis, during the evolution of a case of Rosai Dorfman Disease (RDD). A 44-year-old male patient with RDD affecting the salivary glands, cervical lymph nodes, nasal and maxillary sinus mucosa had a waxing and waning course over two and a half years, with episodic sudden increase in size followed by involution and then a static course with moderate sized swellings. Multiple aspirations and biopsies were performed, which form the basis of this study. Four classical cases of RDD on aspirates and another four on biopsy were analyzed for comparison, with quantification of the number of lymphocytes engulfed by histiocytes (emperipolesis). Three nasal biopsies and one salivary gland excision of the index case, performed during acute exacerbation, showed chronic inflammation and foamy histiocytes without emperipolesis, the aspirate showing emperipolesis nil in 45%, 1-3 lymphocytes in 15%, 4-10 in 36% and > 10 in 4%. Two aspirations and one lymph node biopsy done from static phase showed classical features of RDD with extensive emperipolesis, the aspirate from left cervical lymph node showing emperipolesis nil in 2%, 1-3 in 5%, 4-10 in 35% and > 10 in 58% while right cervical lymph node aspirate showed emperipolesis nil in 9%, 1-3 in 21%, 4-10 in 29% and > 10 in 41%. A biopsy performed from involuting cervical lymph node showed extensive apoptosis and vasculitis without foamy histiocytes or emperipolesis. For comparison, eight classical RDD cases showed abundant emperipolesis with mild variation. Emperipolesis is variable in RDD depending on disease activity, which has differential diagnostic relevance and demonstrates the natural history of this rare disease.

Our objective was to determine the human papillomavirus (HPV)-type prevalence in cervical samples in women with and without cervical neoplasia in an opportunistic hospital-based cancer-screening program. A cross-sectional study of 524 women presenting from January 2003 through June 2005 with symptoms of persistent vaginal discharge, intermenstrual bleeding, and postcoital bleeding or detected to have an unhealthy cervix underwent HPV genotyping by consensus polymerase chain reaction and reverse line-blot hybridization assay, conventional Pap smear, and colposcopy, with directed biopsy from all lesions detected. The prevalence rates of HPV infection among women with normal, low-grade cervical neoplasia (CIN 1) and high-grade CIN (>CIN2) were found to be 7.6%, 42.3%, and 87.5%, respectively. Seventeen high-risk and 6 low-risk HPV types were identified by the reverse line-blot assay. Multiple infections were seen in 20% of women. In normal women, the 6 commonest types were HPV-16, HPV-89, HPV-39, HPV-52, HPV-62, and HPV-18, whereas in high-grade disease, these were all high-risk types HPV-16, HPV-18, HPV-33, HPV-39, HPV-35, and HPV-56. HPV-16 was the commonest type in all groups, seen in 49.4% cases overall and in 74.3% of high-grade squamous intraepithelial lesion. It was followed by HPV-18 (7.4%) and HPV-33 and HPV-39 (4.9% each). HPV-89 was the commonest low-risk type (9.9%). HPV-16/18 were associated with 34.3% of normal, 45.4% of low-grade and 65.7% of high-grade lesions. A wide spectrum of HPV types is seen in north Indian women, with the majority being HPV-16 in all grades of histology. A vaccine against HPV-16 and HPV-18 could prevent two thirds of cases of high-grade cervical neoplasia.

Mixed serous neuroendocrine neoplasms are extremely rare tumors that are usually seen in female patients and are often associated with von Hippel Lindau (VHL) disease. We describe the case of a 38-year-old male who presented with complaints of anorexia, weight loss, and abdominal pain. CT abdomen showed a mass in the head of the pancreas, multiple small nodules in the body of pancreas, and bilateral adrenal masses. Fine needle aspiration cytology (FNAC) from the mass showed features of a neuroendocrine tumor, with many of the cells demonstrating abundant clear cytoplasm. Histopathological examination of the pancreaticoduodenectomy specimen showed a mixed serous neuroendocrine neoplasm with two components viz. serous cystadenoma and neuroendocrine tumor (NET) World Health Organization (WHO) grade 2. In addition, he was diagnosed to have bilateral pheochromocytomas and a paraganglioma. The synchronicity of these tumors suggested the possibility of VHL disease. Thus, identification of a NET with clear cells or of a mixed serous neuroendocrine neoplasm should raise suspicion of VHL disease. In a mixed tumor, FNAC may identify only one of the two components. Thorough processing of all pancreatic serous tumors for pathological examination is recommended, as NET may occur as a small nodule within the serous cystadenoma.

Background Oncocytic carcinoid tumor of the lung is a rare variant of pulmonary carcinoid. This report describes the morphologic appearance of this rare tumor on filter membrane preparation along with potential pitfalls. Case A 49-year-old woman presented with cough and expectoration. On chest radiograph a mass lesion was seen in the upper zone of the right lung. Bronchial washings were sent for evaluation. On filter membrane (Millipore) preparation of bronchial washings the possibility of a non-small cell carcinoma, possibly squamous, was suggested. Right upper lobectomy was subsequently performed and a histologic diagnosis of oncocytic carcinoid given. The cytomorphologic features of this tumor on the Millipore preparation were reviewed. Conclusion Differential diagnosis of oncocytic carcinoid should be kept in mind while assessing cytologic material when tumor cells show abundant granular cytoplasm and prominent nucleoli. Oncocytic carcinoid also must be differentiated from oncocytoma and granular cell tumor. Immunocytochemistry and electron microscopy are useful in confirming the diagnosis.

Objective To delineate the cytomorphologic appearances of hepatoblastoma (HBL) in the largest series to date and to evaluate the feasibility of subtyping on fine needle aspiration cytology (FNAC). Study Design Papanicolaou- and May-Grunwald-Giemsa-stained smears of aspirates from 26 cases of HRL were analyzed by 2 observers, Histologic material, available in 15 cases, was correlated. A cytology group-ing system was proposed on the basis of which all cases were classified. Results The ages of the patients ranged from 4 months to 9 years. Twenty-five cases were categorized as epithelial HBL, with epithelial fragments showing a trabecular arrangement and acinar formation in all, and extramedullary hemopoiesis in 20 cases. It was possible to differentiate fetal and embryonal areas on FNAC. Six cases showed only fetal elements (cytology group F), characterized by cells with abundant cytoplasm and a small, rounded nucleus resembling a normal fetal hepatocyte. The chromatin was finely granular, with a single, central nucleolus. Pleomorphism and mitoses were not seen, and the nuclear/cytoplasmic ratio was ≤ 1/3. Fourteen cases showed, in addition to fetal elements, an embryonal component characterized by cells with scant cytoplasm, a pleomorphic nucleus, N/C ratio of ≥ 3/1, coarsely granular chromatin and 2-4 angulated nucleoli. Mitoses were seen in these cells (1-4/1,000 cells). Of these 14 cases, 6 showed predominantly fetal and scant embryonal cells, while 8 cases showed fetal and embryonal components in equal amounts (cytology groups Fe and FE, respective-ly). Four cases showed predominantly embryonal cells (cytology group E). One case was unclassifiable (U). On histology, 8 of 14 cases were of mixed epithelial and mesenchymal type, but mesenchymal tissue was not seen on the corresponding cytology. The cytology grouping system correlated well with histology. One case was small cell undifferentiated HBL and resembled a round cell tumor without differentiation. Macrotrabecular arrangement was not seen on cytology but was seen on histology in I case. Conclusion Epithelial HBL can be easily diagnosed in aspirates and further classified into fetal and embryonal subtypes, -which may be of prognostic relevance. The proposed cytology grouping system is effective in semiquantification of the observed subtypes.

The largest series, to date, of fine-needle aspiration cytology (FNAC) findings in clear-cell sarcoma of the kidney (CCSK) is presented. All fine-needle aspirates of pediatric renal masses over a 17-yr period were reviewed. Eight out of 119 aspirates from late-stage childhood renal tumors (6.72%) were found to be CCSK. Ten aspirates from these eight patients and histopathological confirmation in six patients were available. Aspirates were cellular with three cell types: cord cells, septal cells, and small pyknotic cells. Cord cells, seen in all aspirates, were large polygonal cells with abundant eccentrically placed wispy cytoplasm, round to oval nuclei, and fine dusty chromatin. Occasional bare nuclei and frequent nuclear grooves were also seen. Small pyknotic cells were a degenerative change identified in 9 out of 10 aspirates. Stromal fragments with branching vascular cores were seen in 8 out of 10 aspirates, 6 of which had myxoid substance surrounding the vessel. Septal cells were spindle shaped and usually embedded in the stromal fragments. On the basis of cytology and histology, cases were classified into classical CCSK (5 cases), spindle-cell CCSK (1 case), and anaplastic CCSK (2 cases). Classical CCSK showed mostly cord cells with few stromal fragments. Spindle-cell CCSK showed preponderance of myxoid stromal fragments and septal cells. Anaplastic CCSK showed bizarre pleomorphic nuclei, coarse chromatin, and atypical mitosis. Cytology of CCSK is a spectrum with varying proportions of cord cells, septal cells, and mucopolysaccharide substance. Anaplastic CCSK is liable to misdiagnosis as Wilms tumor (WT) with unfavourable histology. Presence of eccentric cytoplasm in cord cells and nuclear grooves are the key to differentiation from Wilms tumor, including anaplastic variants.

Background Nocardiosis is an uncommon infection and presents as an opportunistic infection in an immunocompromised host. Pulmonary infection by Nocardia may be difficult to diagnose based on clinical and radiologic features, as these are not specific. Sputum examination, bronchoalveolar lavage and transthoracic ultrasound/computed tomography-guided fine needle aspiration cytology offer a simple means of procuring material for diagnostic evaluation. Very few articles have described the morphologic appearance of this uncommon pathogen in cytologic material. Cases Three cases occurred in patients with an underlying immunocompromised state. Patient 1 was on steroid therapy for nephrotic syndrome, patient 2 was on immunosuppressant therapy after renal transplantation, and patient 3 was HIV positive. A diagnosis of pulmonary nocardiosis was suspected on Papanicolaou stain. Modified Ziehl-Neelsen stain and silver methanamine stains were useful in confirming the diagnosis. Conclusion A high index of suspicion for nocardiosis must be maintained while assessing cytologic material in immunosuppressed individuals as it may be masked by the intense inflammatory exudate associated with this infection. A meticulous search may reveal the presence of delicate, thin, faintly stained, branching filaments of Nocardia on routine Papanicolaou stain. Special stains and culture studies are useful in confirming the diagnosis.

Giant cell tumor of tendon sheath (GCTTS) is a unique soft tissue lesion of the hands and feet. As the cytomorphological features of this lesion are rarely documented, the spectrum of cytomorphological features in 20 cases of GCTTS seen in fine-needle aspiration (FNA) smears are presented. Patients were in the 12-64-yr age group with an equal sex ratio. Fingers or thumb were the commonest site (16 cases), followed by foot (3 cases) and palm (1 case). FNA smears were cellular and composed of varying proportions of stromal and giant cells. Stromal cells showed a dispersed arrangement and were polygonal to spindle shaped. Nuclear grooves and convolutions were found in some of the stromal cells in all cases. Intranuclear cytoplasmic inclusions were occasionally seen. Polygonal cells with round nuclei and nucleoli having abundant cytoplasm, along with binucleate forms, were also found in all cases. Histological sections were available in 10 cases and corroborated the cytological features. Hemosiderin-laden macrophages (11 of 20 cases) and abundant foamy vacuolation of stromal cells (3 of 20 cases) were also observed in FNA smears. In tissue sections, both features were seen in all cases, but with a patchy distribution. The cytological features of GCTTS are uniform, and FNA cytodiagnosis is possible.

Background: Anaplastic large-cell lymphoma (ALCL) is a rare subtype of non-Hodgkin's lymphoma (NHL) characterized by the presence of unusual giant cells. It is a CD30+lymphoma of T-cells lineage, which shows anaplastic lymphoma kinase-nucleophosmin (ALK-NPM) rearrangement. ALCL on fine needle aspiration cytology (FNAC) shows unusually large and bizarre tumor cells. Materials and Methods: All aspirates seen over a 6-year period from November 2009 to November 2015 in which a diagnosis of ALCL or Hodgkin's lymphoma (HL) with bizarre giant cells were suspected on cytomorphology were prospectively selected. Twenty such aspirates were subjected to CD-30 and ALK-1 immunocytochemistry (ICC). Subsequent biopsy was available in all cases. Results: Out of 20 cases, seven cases, suspected to be ALCL on FNAC, were confirmed on biopsy. ALK-1 was positive in both cytology and biopsy of 6/7 of these. Two cases suspected to be ALCL on cytomorphology were HL (1) and diffuse large B-cell lymphoma (DLBCL) (1) on biopsy, both of which were ALK-1 negative on cytology. Eight cases of HL and three cases of large-cell NHL, which were all ALK negative on cytology, were confirmed on biopsy. Conclusion: ICC for ALK and CD30 is useful in aspiration cytodiagnosis of ALCL. One CD30 positive DLBCL and one ALK negative ALCL showed concordant results of ICC on cytology and histology.

A 58 years old lady reported with history of progressively increasing lump in the neck. Patient had earlier undergone sub-total thyroidectomy (details not available) in a private institute one year back. Fine needle aspiration cytology (FNAC) of the present lump revealed features of papillary carcinoma thyroid. Patient subsequently underwent total thyroidectomy along with excision of a tumor nodule in the larynx. Gross examination of the specimen revealed a tumor nodule in the right lobe of the thyroid. Microscopic examination of the tumor nodule in the thyroid and larynx revealed a columnar cell variant of papillary carcinoma thyroid. Very few reports describing the cytomorphologic features of this variant of papillary carcinoma are available in the published literature. These reports highlight the absence or paucity of nuclear grooves and intranuclear inclusions in this variant. We describe a case of columnar cell variant of papillary carcinoma where nuclear grooves were prominently seen. In addition, we report the occurrence of rosette-like structures which were brought out better on FNA smears. These rosette-like structures have not been emphasized earlier in the published literature. The cytomorphologic features of this rare variant are also reviewed in this report.

The cell block (CB) is a routine procedure in cytopathology that has gained importance because of its pivotal role in diagnosis and ancillary studies. There is no precise review in the published literature that deals with the various methods of preparation of CB, its utility in diagnosis, immunocytochemistry (ICC) or molecular testing, and its drawbacks. An extensive literature search on CB in cytology using internet search engines was performed for this review employing the following keywords: cell block, cytoblock, cytology, cytopathology, methods, preparation, fixatives, diagnostic yield, ancillary and molecular studies. Ever since its introduction more than a century ago, the CB technique has undergone numerous modifications to improve the quality of the procedure; however, the overall principle remains the same in each method. CBs can be prepared from virtually all varieties of cytological samples. In today's era of personalized medicine, cytological specimens, including CBs, augment the utility of cytological samples in analysing the molecular alterations as effectively as surgical biopsies or resection specimens. With the availability of molecular targeted therapy for many cancers, a large number of recent studies have used cytological material or CBs for molecular characterization. The various techniques of CB preparation with different fixatives, their advantages and limitations, and issues of diagnostic yield are discussed in this review.

Objectives: Flexible bronchoscopy with exfoliative cytology is an important tool for the diagnosis of pulmonary fungal infections. The question of colonization versus true fungal infection is of critical importance. Study Design: A 5-year retrospective analysis of all cases of pulmonary fungal infection diagnosed using exfoliative cytology was performed. Clinical, radiological, bronchoscopy and histopathology findings were recorded. Results: A total of 69 cases of mycoses were retrieved. The most common fungal organism identified was Aspergillus followed by Candida and Pneumocystis. Most cases of Aspergillus and Candida in cytological specimens presented as a pulmonary mass or endobronchial growth and were diagnosed as carcinomas in biopsy specimens, thus representing colonization. All cases of Pneumocystis with bilateral ground glass infiltrates and cryptococcosis with parenchymal mass lesion in radiology represented true infection. Histoplasma was identified in pleural fluid from a known case of lung carcinoma. Conclusion: Aspergillus and Candida species are the most common fungal organisms. Most of these represent colonization of malignant growths. However, true fungal infections may also present as mass lesions and may masquerade malignancy clinically. Fluid cytological examination is an important diagnostic modality for pulmonary mycoses; however, it is important to correlate results with clinical, bronchoscopy and biopsy findings for accurate diagnosis and appropriate management.

PubMedID: 22011444 Background: The frequencies of various causes of pulmonary granulomas in pathological material are unknown, as is the influence of geographical location on aetiology. The aim of this study was to identify the causes of pulmonary granulomas in pathological specimens, to define their frequencies, and to determine whether these causes vary by geographical location. Methods: 500 lung biopsies and resections containing granulomas were reviewed retrospectively by expert pulmonary pathologists from 10 institutions in seven countries. Fifty consecutive cases from each location were assigned a diagnosis based on histological features and available clinical/microbiological data. Results: A specific cause was identified in 58% of cases (290/500), most commonly sarcoidosis (136, 27%) and mycobacterial or fungal infections (125, 25%). Mycobacteria were identified in 19% of cases outside the USA versus 8% within the USA. In contrast, fungi accounted for 19% cases in the USA versus 4% in other locations. Fungi were mostly detected by histology, whereas most mycobacteria were identified in cultures. In 42% of cases (210/500) an aetiology could not be determined. Conclusions: Across several geographical settings, sarcoidosis and infections are the most common causes of pulmonary granulomas diagnosed in pathological specimens. Fungi are more commonly identified than mycobacteria in the USA, whereas the reverse is true in other countries. A definite aetiology cannot be demonstrated in more than a third of all cases of pulmonary granulomas, even after histological examination. These findings highlight the need to submit material for histology as well as cultures in all cases in which granulomatous disease enters the differential diagnosis.

Extramedullary deposits may be the presenting feature of acute myeloid leukemia. An early and accurate diagnosis on cytology will aid in correct patient management. This is especially true for patients with acute megakaryoblastic leukemia (AML M7), where bone marrow aspiration may yield only a dry tap. While cytomorphological features of myeloid sarcoma of other types are well recognized due to its rarity, there are only two case reports discussing the morphological details of megakaryoblastic differentiation on aspiration cytology. We present the case of a 25-year-old patient with extramedullary involvement of lymph node and cerebrospinal fluid by AML M7, describing in detail, the morphological features on aspiration as well as exfoliative cytology.