Cerebrospinal fluid infiltration by chronic myeloid leukaemia: Evaluation of cytomorphological features.

BACKGROUND AND AIM: To describe the cytomorphological findings of all cerebrospinal fluid (CSF) cytology samples showing infiltration by chronic myeloid leukaemia (CML) and their correlation with haematological findings. MATERIALS AND METHODS: A retrospective analysis of all CSF samples reported as showing infiltration by CML on cytology from January 2014 to December 2021 was performed. RESULTS: A total of 10 cases with positive CSF cytology were evaluated. The mean age of the patients was 34.1 years (range 17-70 years). There were more males than females. All cases were pre-diagnosed cases of CML on haematological investigations. On cytology, the smears showed atypical/immature blast-like cells, with a high nucleo-cytoplasmic ratio, opened-up chromatin, 1-2 conspicuous nucleoli and a scant to moderate amount of agranular to fine granular cytoplasm along with occasional granulocytic precursors. The shortest time interval for CSF positivity in a known case of CML was 5 months, and the longest interval was 11 years. CONCLUSION: It is extremely uncommon to encounter CML infiltration in CSF. Timely analysis of CSF cytology samples can allow quick diagnosis and alter the patient management protocol.

Neither Russell nor Magenta bodies: A cytological dilemma in breast fine needle aspiration cytology.

Neuroendocrine neoplasms (NENs) are a rare heterogeneous group of breast epithelial tumours showing predominant NE differentiation. NENs of the breast account for less than 1% of all NENs. The index case calls for recognition of these tumours using morphology adjunct with ancillary techniques such as immunohistochemistry on FNA cell blocks.

Identifying the primary site of malignancy in carcinomatous serous effusions using immunocytochemistry.

INTRODUCTION: Malignant effusions are commonly encountered in day-to-day cytology practice. Determining the primary site of malignancy in carcinomatous effusions is a Herculean task. Cytology coupled with immunocytochemistry (ICC) is often found to be helpful in this context. MATERIALS AND METHODS: This study was conducted to evaluate the diagnostic utility of ICC on sections from cell blocks (CBs) in the detection of the primary site of origin in cases of metastatic carcinomatous effusions. To determine the origin of the primary tumour, TTF1 (lung), PAX-8 (ovary), CDX2 (colorectal), GATA3 (breast), and CK19 (pancreaticobiliary) were employed, depending on the clinical and radiological findings, and serum tumour markers. RESULTS: A total of 13,459 serous effusion samples were received for cytological evaluation from January 2017 to December 2021, of which 2708 (20.1%) were carcinomatous effusions. Out of these, 1044 (38.5%), 1611 (59.5%), and 53 (2.0%) were from pleural, peritoneal and pericardial cavities, respectively. Of these, the majority were adenocarcinoma. ICC was performed in 309 (11.4%) cases. The ovary was the most common primary site in 179 cases (57.9%), followed by the lung (75, 24.3%), pancreaticobiliary system (12, 3.9%), colon/rectum (8, 2.6%), breast (6, 1.9%), prostate (2, 0.6%) and kidney (1, 0.3). The lung was the most common primary site in pleural (67/113, 59.3%) and pericardial (6/8, 75%) effusions. The ovary (168/188, 89.4%) was the most common primary site for carcinomatous effusions in the peritoneal cavity. However, in 17 (5.5%) cases, the exact primary site could not be established. CONCLUSIONS: Judicious and methodical use of ICC on CBs helps to identify the primary site of the tumour in most carcinomatous effusions. This is of immense help to the treating clinician in directing appropriate therapy.

Metastatic germ cell tumour in effusion cytology.

BACKGROUND: Germ cell tumours infrequently metastasise to body cavities, where early detection on fluid samples is possible and can spearhead early treatment and survival. MATERIALS AND METHODS: A total of seven cases of metastatic germ cell tumours were retrieved out of 7500 effusion samples received for cytopathological examination from 2015 to 2021. Detailed cytological features of metastatic germ cell tumours in effusion samples were studied, along with a correlation between clinical, radiological, and histopathological features. RESULTS: A total of seven cases of metastatic germ cell tumours were analysed in effusion samples which included dysgerminoma (2), immature teratoma (2), yolk sac tumour (1), embryonal carcinoma (1), and mixed germ cell tumour (1). The smears showed predominantly discrete or loose clusters of cells. The cells with round nuclei and prominent nucleoli were helpful in detecting dysgerminoma and yolk sac tumours. Immature teratoma showed tiny groups of small cells and mature squamous cells. Serum tumour markers were raised in the majority of cases. CONCLUSION: Metastatic germ cell tumours in effusion are uncommon, but detailed clinical history, including serum markers and characteristic cytological features, are helpful in their diagnosis.

Differentiating benign and malignant pancreatic masses: Ga-68 PSMA PET/CT as a new diagnostic avenue.

OBJECTIVE: Differentiation of malignant and benign pancreatic lesions on anatomical imaging is difficult in some cases with overlapping features. Prostate-specific membrane antigen (PSMA) is overexpressed during angioneogenesis in many tumors. We aimed to evaluate the PSMA expression in pancreatic lesions to differentiate these lesions and explore the performance of Ga-68 PSMA-PET/CT vis-a-vis F-18 FDG-PET/CT. METHODS: Patients with pancreatic lesions on conventional imaging were prospectively recruited. All the patients underwent a whole-body F-18 FDG-PET/CT and a regional abdominal Ga-68 PSMA-PET/CT. Focal tracer uptake (FDG or PSMA) on PET images was considered positive. Histopathology and/or cytopathology were considered the reference standard. RESULTS: A total of forty patients (27 males, mean age 55.3 ± 9.8, range 37-71 years) were enrolled. Of these, 19 were diagnosed as malignant on histopathology/cytology. Patients with benign lesions showed no worsening of symptoms for at least 6 months on follow-up. FDG-PET/CT revealed 17 true-positive (TP), 9 false-positive (FP), 12 true-negative (TN), and 2 false-negative (FN) findings, whereas PSMA-PET/CT had 18 TP, 2 FP, 19 TN, and 1 FN finding. The sensitivity, specificity, PPV, NPV, and accuracy for FDG-PET/CT were 89.5%, 57.1%, 65.4%, 85.7%, and 72.5%, respectively, while for PSMA-PET/CT were 94.7%, 90.5%, 90%, 95%, and 92.5%, respectively. ROC curve analysis showed that the SUVmax value of 4.8 on PSMA-PET/CT could predict the malignant potential of a lesion with a specificity of 90.5% and a sensitivity of 84.2%. CONCLUSIONS: Ga-68 PSMA-PET/CT imaging helped in establishing a non-invasive pre-operative diagnosis of primary pancreatic malignancy with a higher degree of specificity and accuracy compared with FDG-PET/CT. KEY POINTS: • Conventional imaging such as CT and MRI are unable to reliably differentiate localized malignant pancreatic lesion from benign lesions mimicking malignancy such as mass-forming pancreatitis. • FDG PET/CT helps in detecting malignant foci in view of their increased glucose metabolism. However, it may be falsely positive in inflammatory lesions which may occasionally hinder its ability to differentiate between benign and malignant lesions. • Apart from prostatic malignancy, PSMA is overexpressed in neovasculature of many non-prostatic malignancies. The present study highlights that Ga68 PSMA PET/CT performed better in diagnosing malignancy non-invasively than FDG-PET/CT with a higher PPV (90.5% vs. 65.4%) and accuracy (92.5% vs. 72.5%).

Diagnostic accuracy and cytomorphological spectrum of Wilms tumour in fine needle aspiration biopsy cytology samples supplemented with cell blocks.

OBJECTIVE: Paediatric malignant renal neoplasms are subjected to neoadjuvant chemotherapy as per Societe Internationale d'Oncologie Pediatrique; International Society of Pediatric Oncology (SIOP) protocol. An accurate tissue diagnosis is required prior to institution of chemotherapy, and hence the aim of this study was to evaluate the diagnostic accuracy of fine needle aspiration biopsy cytology (FNABC) along with cell block histology. MATERIALS AND METHODS: A retrospective audit of all paediatric renal neoplasms diagnosed by FNABC between 2015 and 2019 was performed. Histopathology correlation was done wherever available. WT cases were subjected to detailed cytomorphological evaluation. RESULTS: A total of 121 cases of paediatric renal neoplasms including 109 WT, four clear cell sarcoma, one malignant rhabdoid tumour and three mesoblastic nephroma were evaluated. The age range was 4 weeks to 8 years. FNABC samples were adequate for diagnosis in 120 of 121 cases (99.18%) and a definitive cytological diagnosis was achieved in 117 cases (96.7%). The specificity and sensitivity for a cytopathological diagnosis of WT were 98.7% and 97.4%, respectively. On detailed cytomorphological analysis of 68 histopathology-proven WT, 40 (58.8%) cases were triphasic, 23 (35.3%) were biphasic and four were composed of blastema only. The corresponding cell blocks provided additional information over the conventional smears in 23 (33.8%) cases, with epithelial or mesenchymal elements recognised and evidence of rhabdomyoblastic differentiation. CONCLUSION: FNABC along with cell block histology is highly accurate for diagnosis of WT and other malignant paediatric renal neoplasms and is recommended as the technique of choice in centres with cytopathology expertise for establishing a cellular diagnosis prior to commencement of neoadjuvant chemotherapy.

'Rollover' abdominal paracentesis versus standard technique: protocol of a crossover randomized comparative trial.

The sensitivity of single abdominal paracentesis for diagnosis of peritoneal carcinomatosis in patients with malignant ascites is 40-70%. Tumor cells shed from the peritoneum settle preferentially in certain recesses of the peritoneum. We aim to compare the standard technique of abdominal paracentesis versus a rollover technique in a randomized crossover study to assess the cytological yield in patients suspected to have peritoneal carcinomatosis. Each patient will serve as their own control and the outcome assessor (cytopathologist) will be blinded to the method of paracentesis performed. The primary objective will be to compare the tumor cell positivity between the standard paracentesis group and the rollover group among enrolled patients. Clinical Trial registration: CTRI/2020/06/025887 and NCT04232384.

Lay abstract Existing methods of diagnosing cancer-related ascites are dependent on microscopic evaluation of fluid obtained from the ascites. However, this may not diagnose all such cases because the fluid may not contain many tumor cells. This may be due to the settling of tumor cells in certain inaccessible locations of the peritoneum (the lining of the abdominal cavity). This trial will look at whether rolling the patient from side to side could be helpful in increasing the chances of finding tumor cells in the ascites.

Clinical and morphological spectrum of cutaneous metastases on cytology: A study of 225 cases.

INTRODUCTION: Any type of cutaneous metastasis indicates dismal outcome of the disease. Skin is an unusual location for metastatic deposits from any tumour and has an incidence of about 0.8%-5%. Fine needle aspiration cytology (FNAC) helps in the rapid diagnosis of metastasis with minimum pain. AIM: To study the cytomorphological spectrum of cutaneous metastasis on FNAC. MATERIAL AND METHODS: A total of 225 patients with diagnosis of cutaneous metastasis on cytology were analysed. May-Grünwald Giemsa and haematoxylin-eosin-stained smears were studied and examined for the cytomorphological spectrum of cutaneous metastasis. Cell block was prepared in a few cases. In a subset of cases, immunohistochemistry was done to pinpoint the primary. RESULTS: Amongst the 225 patients studied, the mean age was 53.9 years. There was female preponderance with 125 females and 100 males. The commonest site was abdominal wall (n = 89) followed by chest wall (n = 60). The most common type of metastasising tumour was adenocarcinoma. CONCLUSION: Clinicians and pathologists must be aware of the clinico-morphological spectrum of cutaneous metastasis for instant diagnosis followed by prompt management.

Fine needle aspiration cytology with the aid of immunocytochemistry on cell-block confirms the diagnosis of solid pseudopapillary neoplasm of the pancreas.

INTRODUCTION: To determine the diagnostic efficacy of fine needle aspiration cytology (FNAC) in cases of pancreatic solid pseudopapillary neoplasm (PSPN) with emphasis on the cytomorphological features and to evaluate the contribution of immunocytochemistry on FNAC cell-block (CB) in cases of PSPN. METHODS: It is a retrospective study in which ultrasound-guided FNAC of pancreatic lesions diagnosed as PSPN between years 2009 and July 2019 were reviewed along with cytohistological correlation. Immunocytochemistry on CB was performed, wherever required. RESULTS: A total of 16 patients with a cytological diagnosis of PSPN of the pancreas were identified. The most common cytological findings were characteristic branching pseudopapillary fragments with central thin, delicate capillaries associated with the amorphous myxoid substance, surrounded by tumour cells with mild pleomorphism. Immunocytochemistry was performed on CB of six cases. The tumour cells revealed nucleocytoplasmic positivity for ß-catenin, cytoplasmic positivity for vimentin, membranocytoplasmic positivity for CD10 and nuclear positivity for progesterone receptor in all the cases, while they were negative for chromogranin, CD56, pan-cytokeratin and epithelial membrane antigen. The resected histopathological specimen was available in 10cases, and all were confirmed as PSPN. CONCLUSION: Although PSPN has a characteristic cytomorphology, cell-block immunocytochemistry on FNA material confirms the diagnosis in problematic cases and excludes other pancreatic tumours, thus helping in appropriate management.

Ultrasound-guided fine needle aspiration of ovarian masses: Assessment of diagnostic accuracy and risk stratification using a categorical reporting system.

INTRODUCTION: The present study was undertaken to assess the accuracy of fine needle aspiration cytology (FNAC) and cell-block immunocytochemistry, and to estimate the risk of malignancy, using a categorical reporting system, in the diagnosis of ovarian masses. METHODS: This was a 5-year retrospective study of FNAs of ovarian masses. The cytological diagnoses were categorised as inadequate, non-neoplastic, benign neoplasms, indeterminate for malignancy, suspicious for malignancy and malignant neoplasms. The cytology was correlated with the corresponding histopathology to assess the diagnostic accuracy and risk of malignancy associated with each diagnostic category. RESULTS: Of a total of 66 703 FNAs performed during the study period, 580 (0.9%) were performed on ovarian masses. Of these, 40 (6.9%) were reported as non-neoplastic; 76 (13.1%) as benign neoplasms; 14 (2.4%) as indeterminate for malignancy, 48 (8.3%) as suspicious for malignancy, 337 (58.1%) as malignant neoplasms and 65 (11.2%) as inadequate for interpretation. Immunocytochemistry (ICC) was performed on 99 (17%) aspirates. Subsequent histopathology was available in 208 (35.8%) cases. On cyto-histopathological correlation, 183 (88%) were concordant and 25 (12%) were discordant. The overall sensitivity, specificity, positive and negative predictive values and diagnostic accuracy for diagnosing ovarian malignancy were 88.4%, 85.7%, 96.8%, 60.0% and 88% respectively. Risk of malignancy for each category was 80%, 0%, 4.5%, 66.7%, 88.5% and 98.5% respectively. CONCLUSIONS: Ultrasound-guided FNAC has high specificity and diagnostic accuracy for preoperative diagnosis of ovarian malignancies and hence is a valid diagnostic procedure in certain clinical situations. Reporting using a categorical system imparts uniformity and also provides the clinicians with an associated risk of malignancy to guide further management.

Fever of Unknown Origin in Older Adults: A Prospective Observational Study from North India.

OBJECTIVES: Fever of unknown origin (FUO) has different etiology in different age groups. We aimed to determine the spectrum of FUO in older patients and to establish the underlying etiology. METHODS: This was a hospital-based prospective observational study conducted between January 2018 to June 2019 at Postgraduate Institute of Medical Education and Research, Chandigarh, India. Fifty-one consecutive patients aged 60 years and above met the qualitative criteria of FUO. RESULTS: The etiological distribution was infections in 21 patients (41.2%), malignancies in 16 (31.4%) and noninfectious inflammatory disorders in 8 (15.7%). Six patients (11.8%) remained undiagnosed. Among infections, 15 patients (29.4%) had tuberculosis, and 10 had an extrapulmonary disease. Twelve out of 16 cases with malignancies had a hematological cause, and eight had lymphoma. ;Regarding decisive methods of diagnosis, 18F-fluorodeoxyglucose positron emission tomography was diagnostic in 17 out of 27 patients (63%) and computed tomography in 21 out of 42 cases (50%). Imaging or endoscopy-guided procedures provided a diagnostic clue in 12 out of 14 patients (85.7%), and bone marrow examination results were useful in 9 out of 19 (47.4%). CONCLUSIONS: Infections and malignancies contributed to about three-fourths of cases, with tuberculosis and lymphoma being the commonest etiologies.

Fine-needle aspiration cytology of extra-salivary adenoid cystic carcinoma.

INTRODUCTION: Adenoid cystic carcinoma (ACC) is a ubiquitous tumour which can occur in several sites of the human body. Commonly, it affects the salivary glands but also can rarely occur in various extra-salivary locations. AIM: To study the clinical and cytological features of extra-salivary ACC on fine needle aspiration cytology. METHODS: In this paper, we included 27 patients with extra-salivary ACC on fine needle aspiration cytology over a period of 5.5 years. The complete cytomorphological spectrum of extra-salivary ACC was studied. RESULTS: The mean age of the patients was 50.2 years, with age ranging between 14 and 80 years. Male to female ratio was 1:1.7 with 17 females and 10 males. The most frequent primary site was the orbit, and the most frequent sites of metastasis were liver and lung. CONCLUSION: Cytopathologists should be alert about the full range of location as well as the cytological spectrum of extra-salivary ACC for greater precision in diagnosis and prompt treatment.

Fine needle aspiration cytology of primary and metastatic gastrointestinal stromal tumour.

AIM: To explore the cytological spectrum of the gastrointestinal stromal tumour (GIST) including its metastatic sites. MATERIAL AND METHODS: A total of 42 patients (45 sites) diagnosed with GIST or its metastases on fine needle aspiration cytology were studied over a period of 5 years. May-Grünwald Giemsa- and haematoxylin and eosin-stained smears were reviewed and analysed for the cytomorphological spectrum of GIST. RESULTS: Primary GIST alone was seen in 24 cases, E-GIST in eight cases and metastasis in 11 cases (one patient showing metastasis at two distinct sites), whereas concurrent primary and metastatic lesions were noted in two cases. Amongst primary sites, the most commonly affected location was stomach (n = 22), followed by ileum (n = 2), duodenum (n = 1) and rectum (n = 1). Extra-GIST was seen in retroperitoneum and pelvis (n = 3 each), omentum and mediastinum (n = 1 each). Fine needle aspiration cytology was done from 11 metastatic sites of GIST which included liver, gall bladder fossa, chest wall, and thigh. The classic spindle cell arrangement was the predominant cytological pattern. About 8.8% cases showed predominant epithelioid cell morphology and 15.5% cases had a mixed cytomorphology comprising of both spindle cell and epithelioid cell patterns. Nuclear pseudoinclusions, perinuclear vacuoles and multinucleation were seen in four cases. Immunocytochemistry on cell-block sections for confirmation was performed in 18 cases and all these cases showed strong c-KIT positivity. CONCLUSION: In this largest case series of cytomorphological diagnosis of GIST, we describe the cytomorphology and immunocytochemistry of primary and metastatic GIST. GISTs with predominant epithelioid cell morphology may pose a diagnostic dilemma therefore in all suspected cases of GIST, immunocytochemistry for c-KIT and/or DOG1 should be employed on cell-block preparations to confirm the diagnosis of GIST.

The chemotherapy response score is a useful histological predictor of prognosis in high-grade serous carcinoma.

AIMS: High-grade serous carcinoma (HGSC) is the most common tubal/ovarian malignant tumour, and usually presents at an advanced stage. Interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT) is being increasingly used for the management of these patients. The chemotherapy response score (CRS) has been proposed for grading the response of tubo-ovarian HGSC to NACT on the basis of examination of IDS specimens. Our aims were to evaluate the CRS in post-NACT cases, assess the interobserver agreement, and correlate it with overall and progression-free survival. METHODS AND RESULTS: The CRS was applied by two independent pathologists on omental and adnexal tumour tissue sections from post-NACT patients with HGSC who had undergone IDS. The assigned primary site of tumour origin was documented. The interobserver agreement and prognostic significance of the CRS were evaluated. There were 103 cases, and in 61.1% of cases a fallopian tubal origin was confirmed. There were 26, 35 and 42 cases with CRSs of 1, 2, and 3, respectively. The interobserver variability for CRS was low (κ = 0.806). The CRS showed a significant correlation with progression-free survival (CRS 1 and 2 versus 3: median survival 16 months versus 18 months; P = 0.004); however, after controlling for debulking status, this association was not significant. The CRS applied to adnexal sections did not show any prognostic significance for either progression-free or overall survival. CONCLUSION: The CRS is an easy and reproducible method for predicting the prognosis in post-NACT HGSC patients.

Cytohistological correlation of urine cytology in a tertiary centre with application of the Paris system.

OBJECTIVES: Urine cytology has a high sensitivity in morphological recognition of high-grade urothelial carcinoma (HGUC) as compared to low-grade urothelial neoplasms. The Paris system (TPS) was designed to standardise the reporting of HGUC on urine cytology. We evaluated the diagnostic efficacy of urine cytology in routine practice with the cytohistological correlation and application of TPS. METHODS: A retrospective review of urine cytology reported from 2014 to 2015 was carried out with cytohistological correlation, wherever available. The cases were also recategorised according to TPS with the calculation of malignancy risk of all categories. RESULTS: More than 4000 specimens from 1396 patients were evaluated. Histopathology was available in 244 cases. Urine cytology had a sensitivity of 70.5%, specificity of 78.4%, with an overall diagnostic accuracy of 71.7%. The urine cytology when categorised by TPS had 0.9% unsatisfactory cases, 75.9% negative for HGUC, 8.5% atypical urothelial cells, 0.2% suspicious for HGUC, 14.1% HGUC and 0.4% cases of other malignancies. The risk of HGUC with each category of negative for HGUC, atypical, suspicious for HGUC, HGUC and other malignancy was 11.6%, 12.3%, 33.3%, 58.8% and 80%, respectively. CONCLUSION: Urine cytology continues to show high diagnostic accuracy for the detection of urothelial carcinoma with a relatively high sensitivity for HGUC. TPS for reporting urine cytology defines specific criteria for diagnosing atypical and HGUC but increases the cases in the atypical category.

Fine-needle aspiration cytology of retroperitoneal myoepithelial carcinoma: A rare encounter with diagnostic dilemmas.

Myoepithelial carcinoma (MC) arises from the myoepithelial cells. It is a rare tumor with a predilection for salivary glands. MC in soft tissue is uncommon. Soft tissue MC exhibits dual epithelial and smooth muscle phenotype. The extremities and limb girdles are commonly affected. We present cytological findings of retroperitoneal MC with an accurate diagnosis being rendered with the aid of immunocytochemistry on the cell block and demonstration of EWSR1 rearrangements by fluorescence in situ hybridization on cytology smear. The smears were cellular, showing loose clusters and sheets of tumor cells embedded in dense eosinophilic to myxoid matrix material. The cells were oval to polygonal, with focal areas showing moderate nuclear pleomorphism, vesicular to coarse chromatin, and vacuolated cytoplasm with clearing. On immunocytochemistry, tumor cells were positive for epithelial membrane antigen, pan-cytokeratin, calponin, smooth muscle actin, and S-100. A literature review shows only a handful of cases of soft tissue MC. The current report emphasizes the need for cytomorphological awareness with the employment of ancillary testing for accurately diagnosing this rare tumor at an uncommon location. We also discuss the diagnostic challenges and troubleshooting.