A Correlation of Tumour Budding and Tumour-Stroma Ratio with Clinicopathological Factors in Oral Squamous Cell Carcinoma.

Objectives: This study aimed to analyse the association of tumour budding (TB) and tumour-stroma ratio (TSR) with clinicopathological parameters that can be easily viewed on routine haematoxylin and eosin (H&E)-stained slides to provide an easy and cost-effective method for prognosticating oral squamous cell carcinoma (OSCC). Methods: This study was conducted at the ESIC Medical College and Hospital in Faridabad, India, from July 2022 to October 2022. In patients with histologically diagnosed OSCC, TB and TSR were evaluated via routine H&E-stained sections and correlated with clinicopathological parameters. Statistical analysis was performed using Chi-squared test. Results: A total of 50 patients were included. The mean age of participants was 61 ± 12.72, and the male-to-female ratio was 7.1:1. Most of the tumours were located on the tongue (46%), followed by the buccal mucosa (26%), gingivobuccal sulcus (12%) and retromolar trigone (8%). The palate and alveolus were the other sites involved, constituting 4% each. TB and TSR were both found to be significantly associated with the tumour grade, lymph node metastasis and tumour size. A highly significant correlation was also found between TB and TSR (P = 0.001). Conclusions: Both TB and TSR can be easily evaluated on routine H&E sections; they are highly reproducible and were found to be reliable independent prognostic markers in OSCC. Therefore, this simple and cost-effective method of prognostication, which is currently lacking in clinical practice, will help clinicians to identify patients with poor prognosis and thus individualise their treatment plan.

COVID-19-associated mucormycosis - "The Black fungus" with associated invasive aspergillosis and actinomycosis infection: Series of 5 cases in the Indian scenario.

COVID-19 caused by SARS-CoV-2 has been studied and reported widely since November 2019, after its first case was detected in Wuhan, China. It has proven to be a fatal disease worldwide. COVID-19 causes severe disease in patients with immunosuppression and has always been associated with high mortality in such patients. Immunocompromised patients are always at a higher risk of getting co-infections too, and the same is true with COVID-19. It predisposes to the development of many fungal infections of which, mucormycosis is one of the most common ones, especially in the Indian population where a large group of the population is predisposed to diabetes mellitus. India has the world's largest population of diabetic patients; therefore, the prevalence of COVID-19-associated mucormycosis (CAM) is also the highest in India. Also, the use of corticosteroids over a long duration of time predisposes the patients to the development of mucormycosis owing to immunosuppression. Hypoxia, low total leukocyte count, and high ferritin are the other predisposing factors that lead to the growth of mucormycosis associated with COVID-19. Here, we present five cases within a span of 2 months, of mucormycosis-associated COVID-19 with mixed infections of aspergillosis and actinomycetes. Four cases had mucormycosis with aspergillosis and one with mucormycosis with Actinomyces. Three patients recovered fully after being treated with intravenous amphotericin B; however, unfortunately, two of our patients could not be saved.

A critical appraisal of mucormycosis in COVID- 19 patients in a tertiary care centre in India.

Background and Purpose: Morbidity and mortality of opportunistic fungal infections in COVID-19 patients are less studied and defined. The patients receiving immunosuppressive therapy, broad-spectrum antibiotics, corticosteroids, and invasive and non-invasive ventilation are the high-risk groups. Materials and Methods: The demographic profile as well as clinical and radiological findings of all the patients with COVID-19 suspected of Mucormycosis (MM) were recorded. The tissue samples from all the patients were sent for microbiological (KOH mount and culture) and histopathological analysis for confirmation of MM. Results: In total, 45 COVID-19 patients suspected of MM were included in the study and MM was confirmed in 42 patients. The mean age of the patients was 50.30±14.17 years with a female: male ratio of 1.1:1. The most common symptom was headache (52.38%) followed by purulent nasal discharge (38.09%) and facial pain in 33.33% of the cases. The ocular symptoms included a diminution of vision (33.33%) and redness of the eye (2.38%). The most common site of involvement was rhino-orbital (42.85%) followed by sinonasal (23.80%) and rhino cerebral (19.04%). Majority (38.09%) of the patients were diagnosed with stage II of Rhino-orbital-cerebral Mucormycosis (ROCM) based on radiology. A history of diabetes mellitus and steroids was present in 97.61% and 85.71% of the cases, respectively. Moreover, KOH was positive for MM in 97.61% of the cases while the culture was positive in only 35.71% of the cases. In addition, on histopathology, MM was confirmed in 64.28 % of the cases. Mixed growth with Aspergillus species and Rhizopus species was observed in 14.28% of the cases in culture and 11.90% of the cases in histopathology test. Furthermore, angioinvasion was found in 23.80% of the cases according to the histopathology test. Conclusion: Based on the results, the most common conditions associated with MM in COVID-19 patients were diabetes mellitus and steroid therapy. A high level of clinical suspicion aided with diagnostic tests, including KOH mount, culture, histopathology, and radiology which helped the early detection of opportunistic fungal infection in COVID-19 patients to ensure timely treatment.

A rare case of complicated malaria presenting as warm autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) has been rarely reported worldwide or from India as the underlying cause of anemia in malaria. We hereby present a case of complicated Plasmodium falciparum malaria with concomitant warm AIHA in a 31-year-old male. Direct Antiglobulin Test (DAT) was positive and elution studies showed pan-agglutination reaction. Clinico-hematological and serological follow-up of the patient was done post artesunate treatment until day 9. We suggest that it is important to establish the immune basis of anemia in malaria patients for guiding the treatment plan for the clinicians and providing packed red blood cell transfusion if required.

Primary leiomyosarcoma of ovary: A rare malignancy as an incidental finding.

Primary leiomyosarcoma (PLMS) of the ovary is extremely rare tumors comprising 1% of ovarian tumors. About 3% of all ovarian malignancies are primary ovarian sarcomas. Only 72 cases have been reported till date. A 57-year-old postmenopausal female presented with abdominal pain for the last 6 months. Ultrasonography and MRI revealed a heterogeneously enhancing solid lobulated mass in the left adnexa abutting the fundus of the uterus and bowel loops. The endometrial cavity was normal. Ovarian markers CA 125, CEA, CA 19.9, and all hematological parameters were within normal limits. LDH was near normal (284 IU/ml). The specimen was sent for frozen section and a diagnosis of malignant spindle cell lesion of ovary was rendered. Histopathology of the ovarian mass revealed intersecting fascicles of tumor cells consisting of ovoid to spindle-shaped cells having a moderate amount of cytoplasm. Bizarre and atypical cells were seen singly dispersed and in small aggregates along with the brisk mitotic activity. Focal areas of necrosis and hemorrhage were also noted. Immunohistochemistry showed strong positivity for smooth muscle actin and Caldesmon while focal positivity for Desmin and Epithelial Membrane Antigen (EMA) was noted. The lesion was negative for Inhibin, Calretinin, and CD 117 and S100. The final diagnosis of primary ovarian Leiomyosarcoma was given based on histopathology and Immunohistochemistry. PLMS of the ovary are rare incidental findings in postmenopausal women. These are highly malignant tumors and carry a poor prognosis. Hence, early diagnosis and surgical treatment with cytoreduction improve patient survival.

COVID-19 Associated Coagulopathy in an Indian Scenario: A Correlation with Disease Severity and Survival Status.

Covid-19 pandemic reveals that the virus causes Covid-19 associated coagulopathy and it is well known that thrombotic risk is associated with ethnicity. To describe the Covid-19 associated coagulopathy in Indian population and to correlate it with the disease severity and survivor status. A cross sectional descriptive study of 391 confirmed Covid-19 cases was carried out over a period of 1.5 months. Patients were categorised as mild to moderate, severe and very severe and also labelled as survivors and non survivors. Prothrombin time (PT), International normalised ratio (INR), activated partial thromboplastin time, D dimer, Fibrin degradation products (FDP), fibrinogen and thrombin time and platelet counts were investigated among the subgroups. Mean age was higher in patients with severe disease (57.62 ± 13.08) and among the non survivors (56.54 ± 12.78). Statistically significant differences in D dimer, FDP, PT, INR and age were seen among the 3 subgroups and survivors. Strong significant positive correlation was noted between D dimer and FDP (r = 0.838, p < .001), PT and INR (r = 0.986, p < 0.001). D dimer was the best single coagulation parameter as per the area under curve (AUC: 0.762, p < 0.001) and D dimer + FDP was the best combination parameter (AUC: 0.764, p = 0) to differentiate mild moderate from severe disease. Raised levels of D dimer, FDP, PT, PT INR and higher age correlated positively with disease severity and mortality in Indian Population.

Association of Hematologic biomarkers and their combinations with disease severity and mortality in COVID-19- an Indian perspective.

BACKGROUND: COVID-19 is a systemic viral infection with a significant impact on the hematopoietic system, hemostasis as well as immune system. It would be of utmost importance to explore if the most routinely used tests could serve as an aid in determining patient's clinical status or predicting severity of the disease. METHODS: A prospective cross-sectional study was conducted on 506 Covid-19 positive patients and 200 controls over a period of two months (June and July 2020). The cases were sub-classified based on disease severity into mild to moderate (n=337), severe (n=118) and very severe (n=51) and based on survivor status into survivors (n=473) and non-survivors (n=33). RESULTS: There were statistically significant differences in WBC count, Absolute neutrophil count (ANC), Absolute lymphocyte count (ALC), absolute monocyte count (AMC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) Red blood cell distribution width (RDW-SD) and RDW CV between covid cases vs controls; among the clinical subgroups and among the survivors and non-survivors. There was a significant strong positive correlation between various parameters, that is, NLR and MLR (r: 0.852, P=0), MPV and PDW (r: 0.912, P=0), MPV and PLCR (r: 0.956, P=0), PDW and PLCR (r: 0.893, P=0). NLR (AUC: 0.676, P=0) was the best single parameter and NLR+RDW-CV was best combination parameter as per area under curve (0.871) of ROC to distinguish severe from mild to moderate disease. CONCLUSIONS: Leucocytosis, neutrophilia, lymphopenia and monocytosis were characteristic findings in covid cases while NLR and NLR+RDW-CV emerged as the most effective single and combination CBC parameters in distinguishing mild to moderate and severe cases respectively.

An analysis of hematological, coagulation and biochemical markers in COVID-19 disease and their association with clinical severity and mortality: an Indian outlook.

BACKGROUND: The "cytokine storm" (CS) in COVID-19 leads to the worst stage of illness which can be controlled only with timely intervention. There is an urgent need to identify laboratory markers of disease progression for optimum allocation of resources in developing countries like India. METHODS: A cross-sectional study was conducted on 100 COVID-19 positive patients over two months. The cases were sub-classified based on disease severity into mild to moderate (n=61), severe (n=26) and very severe (n=13) and into survivors (n=85) and non-survivors (n=15) based on survivor status. These patients were tested for hematological parameters (total blood lymphocyte counts, NLR, PLR, platelet indices etc.), coagulation markers (D-dimer, fibrin degradation products (FDP), fibrinogen etc.) and biochemical markers (LDH, ferritin, IL-6, procalcitonin, hs-CRP). RESULTS: Statistically significant differences were observed in hematological variables (ANC, NLR and ESR), coagulation parameters (D-dimer, FDP, fibrinogen and thrombin time) and biochemical markers (LDH, ferritin, IL-6, procalcitonin and hs-CRP) with regard to subcategories based of disease severity as well as survivor status. There was strong correlation between NLR, D-dimer, IL-6, procalcitonin and ferritin. IL-6 emerged as the single best marker of disease severity (AUC: 0.997, P=0.00), however procalcitonin, LDH, D-dimer, FDP and NLR could also predict severe disease with a good sensitivity and specificity. CONCLUSION: To conclude, study demonstrates a plethora of biomarkers which could be utilized to accurately identify the hyperinflammation and tissue damage reminiscent of cytokine storm in COVID-19 patients so that timely, safe, and effective therapies can be administered to prevent progression and potentially reduce mortality.

Granular Cell Tumor Breast Masquerading as a Malignancy Cytologically: a Rare Case Presenting a Diagnostic Dilemma.

Granular cell tumor (GCT) also known as Abrikossoff's tumor is an uncommon soft tissue tumor of neurogenic origin. GCT of the breast accounts for < 0.1% of breast tumors and 6% of all reported cases of granular cell tumor. Although GCT is a benign tumor, malignant GCT can be seen in 1% v of the cases. GCT of the breast is diagnostically challenging as it can imitate carcinoma clinically and radiologically but need to be differentiated from breast malignancy since they have totally different approach in treatment and prognosis. GCT has a great ability to mimic a variety of lesions from benign histiocytic to malignant epithelial/mesenchymal lesions, thereby presenting a diagnostic challenge to the practicing cytopathologist. We report a case of GCT of breast cytologically masquerading as a malignancy in a 45-year-old female. Although, fine needle aspiration (FNA) is a first-line diagnostic tool, the present case reemphasizes the role of histopathology as the gold standard for a definite diagnosis clubbed with ancillary techniques like immunohistochemistry and special stains.

A Clinicopathological Correlation of International Federation of Gynecology and Obstetrics's PALM-COEIN Classification of Abnormal Uterine Bleeding: Indian Scenario.

BACKGROUND: Abnormal uterine bleeding (AUB) is a common problem affecting the women of reproductive age group and may also have a significant impact on their physical, social, and emotional aspects directly affecting their quality of life. The International Federation of Gynecology and Obstetrics (FIGO) devised a universally acceptable system of nomenclature and classification, namely PALM-COEIN classification of AUB in the year 2011. The objective of the present study was to analyze the structural (PALM) and functional (COEIN) component of FIGO system in the Indian scenario. MATERIALS AND METHODS: Three hundred patients with complaints of AUB were taken. A clinical diagnosis according to PALM-COEIN system was made after thorough history and clinical examination. Additional investigations if required were done, and endometrial sampling or hysterectomy was done whichever indicated. A histological diagnosis was made, and each case was allocated a category according to PALM-COEIN classification. A clinicopathological correlation was done in the hysterectomy cases for structural causes (PALM). RESULTS: Leiomyoma (30%) was the most common cause of AUB closely followed by adenomyosis (29.66%) overall. The clinicopathological correlation in hysterectomy cases was good with concordance rate of 85.03%. The concordance between clinical and pathological diagnoses for AUB-L, AUB-A, AUB-M, and AUB-A, L was statistically significant with P < 05 in positive cases. However, additional finding of adenomyosis was diagnosed in 48.2% of the cases apart from primary clinical diagnosis. CONCLUSION: A good clinicopathological correlation was seen in the cases when classified according to PALM-COEIN classification. The system also provides for consideration of multiple etiologies contributing toward AUB both clinically and histopathologically. However, histopathology remains the cornerstone in establishing the accurate diagnosis as the cases without specific symptoms can be missed clinically.

IAC standardized reporting of breast fine-needle aspiration cytology, Yokohama 2016: A critical appraisal over a 2 year period.

BACKGROUND: Breast cytology is a significant component of the "Triple approach" for pre-operative diagnosis of breast lumps, the other two being clinical assessment and radiological imaging. The role of Fine needle aspiration cytology (FNAC) as a first line investigation in diagnosing breast lesions is well documented, however histopathology is the gold standard. Cyto-histopathological correlation is of great relevance and also increases precision.AIMS \& OBJECTIVES:The present study was conducted with the aim to categorize breast lesions according to the latest standardized reporting system proposed by International academy of cytologists (IAC) in 2016. Evaluation of diagnostic accuracy, sensitivity and specificity of FNAC in diagnosing breast lesions and cyto-histopathological correlation was planned. MATERIALS AND METHODS: All FNAs of breast lesions over a period of 2 years were included in the study. The cases were grouped into five standardized categories proposed by the International academy of cytology: Category I (Insufficient material), Category II (Benign), Category III (Atypical, probably benign), Category IV (Suspicious, probably in situ or invasive) & Category V (Malignant) respectively. Specificity, sensitivity, diagnostic accuracy, negative and positive predictive value of FNAC were calculated and cyto-histopathological correlation assessed wherever possible. RESULTS: Out of 468 breast lesions reported on FNAC, the category wise distribution was - Category I, II, III, IV & V accounting for 23(4.9%), 342(73.07%), 7(1.5%), 11(2.35%) and 85(18.16%) respectively. Histopathology was performed in 331/468 cases with cyto histological concordance of 98.4% and a type agreement rate of 90.9%. The sensitivity, specificity, positive and negative predictive value and diagnostic accuracy was 98.90%, 99.16%, 97.82%, 99.58% and 99.09% respectively. CONCLUSION: FNAC is a simple, reliable, cost effective, first line diagnostic procedure for all breast lumps. In collaboration with physical examination and imaging studies (triple approach), FNAC is a highly sensitive diagnostic tool. Adopting a universally acceptable standardized reporting system for breast cytology can enhance the diagnostic accuracy of FNAC.

Medullary carcinoma of thyroid mimicking Hurthle cell neoplasm on cytology: a diagnostic dilemma.

Medullary carcinoma of thyroid (MCT) is a neuroendocrine neoplasm derived from the parafollicular cells or C cells. It constitutes 5% of thyroid carcinomas. We present a case of 36-year-old female with a left lower lobe thyroid swelling since 8 to 9 years. Swelling was smooth, nontender, and moving with deglutition. Contrast-enhanced computed tomography (CECT) findings were suggestive of malignant thyroid nodule. Fine-needle aspiration cytology (FNAC) smears were highly cellular comprising predominantly Hurthle cells arranged in sheets, clusters, and follicles with few singly scattered cells. Background was hemorrhagic with scant colloids. An impression of follicular neoplasm or suspicious of follicular neoplasm was given with an additional note mentioning that the possibility of Hurthle cell neoplasm could not be excluded. Left hemithyroidectomy was done and sections showed a well-circumscribed tumor suggestive of MCT, which was confirmed based on immunohistochemistry for calcitonin and carcinoembryonic antigen. It is difficult to differentiate MCT from Hurthle cell neoplasm. There may be cellular pleomorphism within a single aspirate, but the presence of mixed cell population is a diagnostic pointer for MCT. In the presence of predominant Hurthle cell population, distinguishing these entities by cytomorphology alone is difficult. Hence, clinical findings and histopathology with immunohistochemistry are mandatory in such cases to reach to a correct diagnosis to ensure proper management.

Are all Granulomatous Mastitis Cases Tuberculous?: A Study on the Role of Cytology in Evaluation of Granulomatous Mastitis.

OBJECTIVE: Granulomatous mastitis is a rare inflammatory condition of the breast clinically mimicking breast carcinoma and pyogenic abscess, thereby creating a diagnostic dilemma. Tuberculous mastitis is a rare clinical entity accounting for approximately 3% of all mammary lesions. All cases of granulomatous mastitis diagnosed cytologically over a period of 3 years were evaluated to ascertain the cases with tuberculous etiology. MATERIAL AND METHOD: Fine needle aspiration cytology of the breast lump was performed and all the cytological parameters were evaluated. Wherever histopathology was available, the diagnosis was confirmed on Hematoxylin & Eosin stained sections and the Ziehl Neelsen (ZN) stain was applied. RESULTS: A total of 10 cases of granulomatous mastitis were diagnosed on cytology during the 3-year period. On cytological smears, four cases showed presence of ill-formed granulomas and one case had scattered epithelioid histiocytes; however, the rest of the cases had well-formed granulomas. Finally, four out of ten cases were labeled as tuberculous mastitis based on the ZN stain/Tuberculosis-Polymerase chain reaction (TB-PCR) and the other six cases were granulomatous mastitis. CONCLUSION: Cytology plays a significant role in the diagnosis of granulomatous mastitis. This study re-emphasizes the role of the cytopathologist in the accurate and early diagnosis of these lesions so that unnecessary surgery can be avoided, and also highlights the fact that all granulomatous mastitis cases are not tuberculous.

A critical appraisal of the Milan system for reporting salivary gland cytology (MSRSGC) with histological correlation over a 3-year period: Indian scenario.

BACKGROUND: Fine needle aspiration cytology (FNAC) is the first line investigation for pre-operative diagnosis of salivary gland lesions, but due to its inherent limitations remains a challenge for the cytopathologists. The recently proposed international risk stratification scheme, the Milan System for Reporting Salivary Gland Cytology (MSRSGC) aims to promote and standardise the communication between cytopathologist and clinician thereby improving patient care. METHODS: A retrospective study of all salivary gland cytology cases was performed over a 3-year period, reviewed by pathologists and categorised into 1 of the 6 diagnostic categories according to MSRSGC, namely, non-diagnostic, non-neoplastic, atypia of undetermined significance (AUS), benign neoplasm, and salivary gland neoplasm of undetermined significance (SUMP), suspicious for malignancy (SFM), and malignant neoplasm. Cyto- histological correlation was done wherever possible. Risk of malignancy (ROM) was calculated for each diagnostic category. RESULTS: Out of a total of 150 salivary FNAC cases, histopathology was available for 64 cases. The sensitivity of FNAC was 81.8%, specificity was 100% while the diagnostic accuracy was 96.9%. The positive and negative predictive values were 100% and 96.4% respectively. The ROM for non-diagnostic, non-neoplastic, AUS, benign neoplasm, SUMP, SFM, and malignant categories were 0%, 10%, 50%, 2.5%, 50%, 100%, and 100% respectively. CONCLUSION: MSRSGC fulfils the critical need for a uniform, internationally acceptable reporting system with ROM specified for each category. However, large scale multi centre studies need to be conducted before its reliability and validity is proven.

Primary cutaneous adenoid cystic carcinoma of the chest wall: a rare entity.

Primary Cutaneous Adenoid Cystic Carcinoma (PCACC) is a rare form of cutaneous carcinoma. It closely resembles adenoid cystic carcinoma of salivary glands. The lesion tends to infiltrate and recur locally but rarely metastasizes to distant organs and lymph nodes. We present here a case of a31-year-old male with complaints of swellings in the chest wall and scalp, progressively increasing in size over a period of 10 years. Clinical diagnosis of sebaceous cysts of scalp and chest wall was made. Histopathology revealed PCACC of the chest wall and dermoid cyst of the scalp.

Cytology of hyalinising trabecular adenoma-like variant of medullary thyroid carcinoma.

Medullary thyroid carcinoma is a rare thyroid neoplasm that can be either sporadic or familial. It occurs in adults, presenting as a solitary cold nodule on thyroid scan. Most are solid, firm, and non-encapsulated, and occur in the mid portion or upper half of the thyroid gland, corresponding to areas with greater numbers of C cells. We present a case of a 36-year-old female with a swelling in the front of her neck for six years. Fine needle aspiration done elsewhere revealed spindle cells, suggestive of a 'spindle cell neoplasm'. The histopathology of the thyroidectomy specimen showed features of a hyalinizing trabecular adenoma-like variant of medullary carcinoma. Subsequently, we performed aspiration on the received specimen and studied the cytological findings. The cytological diagnosis of this variant requires identification of the dual spindle and ovoid cell population and the granular neuroendocrine chromatin.