Artificial Intelligence: Exploring utility in detection and typing of fungus with futuristic application in fungal cytology.

Artificial Intelligence (AI) is an emerging, transforming and revolutionary technology that has captured attention worldwide. It is translating research into precision oncology treatments. AI can analyse large or big data sets requiring high-speed specialized computing solutions. The data are big in terms of volume and multimodal with the amalgamation of images, text and structure. Machine learning has identified antifungal drug targets, and taxonomic and phylogenetic classification of fungi based on sequence analysis is now available. Real-time identification tools and user-friendly mobile applications for identifying fungi have been discovered. Akin to histopathology, AI can be applied to fungal cytology. AI has been fruitful in cytopathology of the thyroid gland, breast, urine and uterine cervical lesions. AI has a huge scope in fungal cytology and would certainly bear fruit with its accuracy, reproducibility and capacity for handling big data. The purpose of this systematic review was to highlight the AI's utility in detecting fungus and its typing with a special focus on future application in fungal cytology. We also touch upon the basics of AI in brief.

Scalp metastasis of pulmonary blastoma-a rare entity: Cytomorphology with differential diagnoses.

BACKGROUND: Pulmonary blastomas are exceptionally rare tumours. These tumours behave aggressively, with a propensity to metastasise to the brain and mediastinum. A definitive diagnosis of pulmonary blastoma is challenging to obtain on cytomorphology alone. CASE REPORT: We herein describe a case of a 59-year-old female who presented with a scalp lesion. The patient was diagnosed to have pulmonary blastoma on histopathology of left lower lobectomy specimen. Fine needle aspiration cytology was done from this recently developed scalp swelling. Cytomorphology supplemented with immunocytochemistry on cell block confirmed the diagnosis of a metastatic pulmonary blastoma. CONCLUSIONS: In a known case of primary pulmonary blastoma, any newly developing lesion at any anatomical site should be carefully evaluated for metastasis. If metastasis is needled and no previous histology is available, it carries a reasonable risk of erroneous interpretation. It is essential not to overlook often subtle biphasic malignant cells on the smears, which otherwise resemble other poorly differentiated tumours. Immunocytochemistry coupled with morphology is confirmatory.

Primary leiomyosarcoma of the parotid gland: Aspiration cytology with emphasis on differential diagnosis.

Most salivary gland neoplasms are of epithelial origin. Sarcomas of the parotid gland, including leiomyosarcoma, are exceedingly rare mesenchymal tumours. A definitive diagnosis of leiomyosarcoma is challenging on cytomorphology alone. We herein describe a case of a 41-year-old woman who presented with parotid gland swelling. The patient was previously diagnosed with leiomyosarcoma of the parotid gland on histopathology. Fine needle aspiration cytology was done from this recurrent swelling. Cytomorphology combined with cell block immunocytochemistry was fruitful in confirming the tumour recurrence. Primary and recurrent/metastatic leiomyosarcoma of the parotid gland is a rarity and cannot be distinguished on cytology. Such a distinction is based on the known history of prior malignancy, which was forthcoming in the present case, or after an exhaustive work-up. Pertinent clinical history and radiology provide leads for the cytopathologist. They must be sought so that immunocytochemistry can be applied judiciously and a precise/nearly precise cytological diagnosis rendered, as it guides patient management. The diagnosis is challenging on cytology as the spindle cell lesions of the parotid gland range from reactive to benign to malignant tumours.

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.

Umbilical metastasis as an initial presentation of gastrointestinal stromal tumour diagnosed on aspiration cytology.

Umbilical metastasis is a rare event, with a majority being adenocarcinomas. Metastatic squamous cell carcinoma, small cell carcinoma, lymphoma, melanoma, and rarely malignant mesenchymal tumours like leiomyosarcoma can occur as umbilical nodules. These often emerge during a known malignancy, but once in a while they may be an initial presentation of an undetected tumour. An extensive literature search failed to reveal a case of gastrointestinal stromal tumour (GIST) with umbilical metastasis as an initial presentation. We believe that this is an exceptional phenomenon. The diagnosis may easily be missed considering the rarity of this occurrence. A history of primary diagnosis of GIST, when available, is helpful. Here we present cytological findings of metastatic GIST presenting as an umbilical lump, where the diagnosis was reached with the help of limited immunocytochemistry. A timely diagnosis is valuable for locating the primary and initiating surgical management, which may have survival benefits for the patient.

Cytology coupled with immunocytochemistry identifies Merkel cell carcinoma: A rare intruder in the cerebrospinal fluid.

Merkel cell carcinoma is an uncommon aggressive skin tumour which is well known for its recurrence and metastasis. Leptomeningeal metastasis involving the cerebrospinal fluid is extremely rare. The diagnosis may easily be missed as it simulates other much more common small round blue cell tumours. A patient history with a primary diagnosis may not always be available. Awareness and cytomorphological vigilance with judicious employment of appropriate immunomarkers on limited cerebrospinal fluid samples is indispensable for reaching the correct diagnosis. The tumour cells are usually monotonous small round cells, singly scattered or arranged in loosely cohesive clusters. Cells have round to elongated nuclei with coarsely granular chromatin, nuclear moulding in places and scanty basophilic cytoplasm. A limited immunocytochemistry panel employing CK20 and CD56, for which the tumour is positive, is confirmatory. We herein present a case of infiltration of cerebrospinal fluid by Merkel cell carcinoma.

Plentiful melanin pigment containing histiocyte-like cells in Coats disease: Awareness avoids diagnostic pitfall.

Coats disease is an exudative retinal vasculopathy characterised by presence of yellow-golden deposits in the retina and retinal detachment. Subretinal fluid drainage performed as a part of therapeutic management makes the fluid amenable to cytological examination. Infection by Toxoplasma may closely simulate the ocular symptoms seen in Coats disease. Awareness of the cytological findings in Coats disease helps to clinch accurate diagnosis. We herein present a case of Coats disease with many histiocyte-like cells with plentiful intracytoplasmic melanin pigment in cytology smears from subretinal fluid, where cytological diagnosis was challenging and a correct diagnosis was made with the aid of ancillary techniques.

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.

Phaeohyphomycosis Caused by Rhytidhysteron rufulum and Review of Literature.

Phaeohyphomycosis is caused by a heterogeneous group of mycelial dematiaceous (phaeoid) fungi, which produce melanin pigment. This condition is often confused with chromoblastomycosis. Rhytidhysteron is a dematiaceous fungus, which has been recently found to be causing human infections. Till date only three cases of infection with Rhytidhysteron rufulum have been reported in the literature. All three cases have been from North India. Hereby, we present another two cases where Rhytidhysteron was isolated. Both the patients belonged to Chandigarh (India) and presented with subcutaneous lesions. The isolates were confirmed by ITS sequencing. Both the patients were immunocompetent and gave no history of trauma or any other predisposing factor. Phaeohyphomycosis are often missed due to lack of knowledge regarding the fungi causing the infections and there is need for clinical, pathological and microbiological correlation for effective diagnosis and treatment in these cases.

Sudden Death Due to Coronary Blockade by Microfilaremia: An Autopsy Report.

Extralymphatic filarial disease has varied clinical manifestations and is largely underestimated worldwide. We report an autopsy case of extralymphatic filarial disease with coronary and pulmonary circulations being involved and causing sudden death. Such an isolated event is, perhaps, rare and has not been reported so far to the best of our knowledge. Microfilaremia on autopsy may be easily missed or overlooked due to unawareness. The present report emphasizes the importance of extensive careful scrutiny of autopsy sections.

Sudden cardiac death in 2 young siblings.

Hypertrophic cardiomyopathy is a disease known for exhibiting phenotypic and genetic heterogeneity. At times, sudden cardiac death may be the first and foremost manifestation of the disease. We report 2 cases of hypertrophic cardiomyopathy causing sudden death, which were diagnosed on autopsy with special emphasis on histopathological findings of this entity. The role of a pathologist cannot be undermined as the disease is a diagnostic challenge often overlooked by the neophytes in the field due to unawareness.

Neuroendocrine tumor of the liver in pregnancy: A very rare case report.

Neuroendocrine neoplasms (NENs) of the liver represent a rare entity. Amongst this group of uncommon diseases primary hepatic neuroendocrine neoplasm (PH-NEN) represent only 0.3% of all NENs. Moreover, PH-NEN has very rarely been reported in pregnancy. We report a 28-year-old young patient with metastatic small cell neuroendocrine carcinoma of the liver complicated with pregnancy. She was evaluated and managed through a multidisciplinary team approach and received two cycles of chemotherapy with a cisplatin/etoposide regimen during the antenatal period and delivered at 37 weeks period of gestation (POG). This case highlights the importance of major challenges faced during the diagnosis and management of this very rare disease in pregnancy and the successful fetomaternal outcome.

Opportunistic microsporidiosis unveiled by fine-needle aspiration cytology of cervical lymph node with literature review.

Microsporidia are highly specialized obligate intracellular organisms closely related to fungi, traditionally linked to diarrheal diseases in acquired immunodeficiency syndrome patients. Over the past two decades, an increasing incidence of extraintestinal infections affecting various organ systems, especially in immunocompromised individuals, has been observed. The report presents a unique case of lymph node microsporidiosis in a 38-year-old male, positive for human immunodeficiency virus, with coinfections of hepatitis B and C. Fine-needle aspiration cytology (FNAC) from cervical lymph node yielded pus-like, necrotic material with periodic acid-Schiff stained smear uncovering small round to oval spores on microscopy suspicious for microsporidia. Based on polymerase chain reaction and sequencing done with aspiration material, the causative agent was identified as Vittaforma corneae. This rare encounter highlights the significance of recognizing unique morphological characteristics of infectious organisms and employing appropriate ancillary techniques for precise identification. The case underscores the crucial role of FNAC in diagnosing opportunistic infections involving the lymph nodes and the growing significance of molecular tests for specific pathogen confirmation.

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.

Antifungal Susceptibility Profile of Clinical and Environmental Isolates of Aspergillus Species From a Tertiary Care Center in North India.

INTRODUCTION: Aspergillus species are ubiquitously found in the environment worldwide and are important causative agents for infection. Drug resistance among Aspergillus species is emerging, hence the present study was undertaken to look for antifungal susceptibility profiles of clinical and environmental isolates of Aspergillus species. MATERIALS AND METHODS: During the period from January 2018 to June 2019, a total of 102 Aspergillus isolates (40 clinical, 40 hospital, and 22 community environment) were tested for antifungal susceptibility testing for determination of minimum inhibitory concentration (MIC)/minimum effective concentration (MEC) as per Clinical and Laboratory Standards Institute (CLSI) M38-A3 method for itraconazole, voriconazole, amphotericin B, and caspofungin. RESULTS: Out of these 102 Aspergillus isolates, A. flavus was the most common species present. Aspergillus species were found to have low MIC values to azoles such as itraconazole and voriconazole except for one clinical isolate, which showed a MIC value of 2 µg/ml to voriconazole. Two isolates were non-wild-type for amphotericin B, but all isolates were wild-type for caspofungin. CONCLUSION: Antifungal susceptibility testing among clinical Aspergillus isolates and environmental surveillance studies in view of emerging drug resistance should be undertaken at a larger scale.

Mucormycosis: Cytomorphological Spectrum in Fine-Needle Aspiration Cytology.

Background: Mucormycosis is a fungal infection that can affect multiple organs. The role of fine-needle aspiration cytology (FNAC) in its diagnosis is not well documented. Aim: The objective of this study was to describe the detailed cytomorphologic features of mucormycosis on FNAC samples. Materials and Methods: A retrospective analysis of all cases diagnosed as mucormycosis on FNAC between January 2014 and July 2021 was performed for detailed cytomorphological evaluation and correlation to clinical data and microbiological studies wherever available. FNA was computed tomography-guided (n = 38), ultrasonography-guided (n = 31) or palpation-guided (n = 12), and slides were reviewed in two cases. Results: A total of 83 cases of mucormycosis were evaluated. An immunocompromised setting was observed in 48 cases. The most common site of FNA was the lung (n = 57) followed by liver, soft tissue, palate, mediastinum, orbital/ocular region, and lymph node. Isolated renal involvement, a unique feature, was seen in seven cases. The aspirates were necrotic to pus-like or blood-mixed particulate. Broad, nonseptate, foldable, ribbon-like fungal hyphae showing right-angled branching were seen. The tissue reaction was predominantly necro-inflammatory (n = 36), bland necrotic (n = 22), mixed inflammatory (n = 16), suppurative (n = 5), necrotizing granulomatous (n = 3), and granulomatous (n = 1). Immunocompromised patients showed mixed inflammatory responses more frequently. Fungal culture was positive for Rhizopus species in 2/13 cases and molecular testing in two additional cases corresponding to Rhizopus and Syncephalastrum spp. Conclusion: FNA provides quick and conclusive diagnosis of mucormycosis from varied anatomic sites enabling prompt institution of therapy. The tissue response is variable and to some extent dependent on the immune status of the patient.