Application of liquid biopsy in lung cancer management.

ABSTRACT: Current advances in the understanding of the lung cancer landscape have drastically changed the approach to treating a patient with lung carcinoma. The field has progressed from analyzing single gene to using advanced techniques like next-generation sequencing and microarray technology. While a tumor tissue sample is considered the gold standard, it has several limitations. The limitations of invasive procedures, long processing periods, inaccessibility, and sample inadequacy are being addressed by sampling biofluids, termed 'liquid biopsy,' which offers a less invasive and more accessible way to obtain tumor-related information. Liquid biopsy has transformed the care of lung cancer patients by directly targeting somatic alterations from tumors. This article provides insights into the biology, technical aspects, limitations, and practical applications of 'liquid biopsy,' focusing on cell-free DNA and circulating tumor DNA in the context of lung cancer.

Multifocal lower limb hemangioendothelioma in a young female: a case report and review of the literature.

A 26-year-old female presented with pain and swelling of distal thigh and distal leg. She was diagnosed with multifocal epitheloid hemangioendothelioma (EHE) and was successfully treated with wide resection of femoral and tibial lesions followed by their reconstruction using vascularised fibular graft and local bone grafting. One year into follow-up, the patient remained asymptomatic with full Range Of Motion (ROM) and full weight bearing walking. This case illustrates a unique multifocal presentation of hemangioendothelioma and early surgical intervention leading to complete recovery, highlighting the importance of early diagnosis and intervention to help improve prognosis and quality of life of the patient.

Case of angioimmunoblastic T-cell lymphoma presenting as peripheral and bone marrow plasmacytosis: A diagnostic conundrum.

ABSTRACT: Angioimmunoblastic T-cell lymphoma (AITL), a subtype of peripheral T-cell lymphoma (PTCL), is associated with unique clinical, morphological, and immunohistochemical features. The peripheral circulation might show presence of an occasional reactive plasma cell but significant plasmacytosis masquerading as plasma cell leukemia is rare. We report a case of AITL in a 42-year-old male, who presented with two-month history of generalized lymphadenopathy. On investigations, he had hypergammaglobulinemia and plasmacytosis in the peripheral blood and bone marrow masquerading as plasma cell leukemia. Immunohistochemistry and serum protein electrophoresis revealed polyclonal nature of plasma cells. Diagnosis of AITL was made on cervical lymph node biopsy. This case highlights the diagnostic challenge faced due to heterogeneity in the clinical presentation and pathological findings and to alert the clinician so that timely accurate diagnosis can be made to initiate the treatment.

Diagnosis of peritoneal metastasis in an unruptured hepatocellular carcinoma on ascitic fluid cytology: A rare scenario with brief review of literature.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy in adults occurring in a background of cirrhosis. Peritoneal dissemination of HCC is an unusual presentation with an incidence of 2%-16%. Peritoneal metastasis of an unruptured HCC is extremely uncommon. Despite low yield, ascitic fluid cytology serves as a valuable tool for diagnostic evaluation in a patient of cirrhosis with suspicion of malignant transformation. We present a rare case scenario in an elderly female with cirrhosis where the diagnosis of peritoneal metastasis was established on ascitic fluid cytology and confirmed by immunocytochemistry. This report illustrates the unique clinical presentation of an unruptured HCC with its cytological features and a brief review of literature.

Vascular tumors of the liver: A brief review.

Vascular tumors of the liver are mesenchymal lesions from endothelial cells. They range from common benign lesions such as haemangioma, intermediate tumors like Kaposi sarcoma, and perivascular epithelioid cell tumor to malignant tumors such as hepatic epithelioid hemangioendothelioma and hepatic angiosarcoma in adults. Pediatric vascular tumors of the liver also include benign, locally aggressive, borderline, and malignant masses with haemangiomas being the most common benign tumors and epithelioid hemangioendothelioma being an uncommon pediatric malignancy. The list of these lesions is completed by nodular regenerative hyperplasia, solitary fibrous tumour, and hepatic small vessel neoplasms (HSVN). Some of these tumors are uncommon and rare. This review article aimed to enumerate hepatic vascular tumors along with their imaging, histopathology, molecular findings for accurate diagnosis that can result in better management.

Neurosarcoidosis - A diagnostic challenge?

Background: Sarcoidosis is an inflammatory granulomatous multisystem disease with an unknown etiology. Neurosarcoidosis is a cryptogenic neuroinflammatory manifestation of sarcoidosis. Objective: This article aims at better understanding of one of the rarer diseases whose diagnosis may be difficult leading to delay in definitive management of the patient. Method: We describe a case of neurosarcoidosis with initial presentation similar to acute invasive fungal rhinosinusitis, whose diagnosis was challenging and delayed owing to the presenting symptoms. Conclusion: The diagnosis of neurosarcoidosis becomes challenging when it presents as isolated clinical neurological symptoms. We want to highlight the variable nature of neurosarcoidosis and its consideration as diagnosis after excluding other common infectious and inflammatory conditions.

Multi-modality management of chondrosarcoma of scapula: A case report and review of literature.

Chondrosarcoma are malignant tumours in which neoplastic cells produce cartilage. The most commonly affected sites are pelvis, femur, humerus and ribs. Scapula involvement is relatively rare. Surgery remains the primary modality of treatment for chondrosarcoma. Radiotherapy is used as an adjuvant therapy in high grade tumours and in cases of residual disease. Present study reports a rare case of scapular chondrosarcoma in a 37 year old male, managed with multimodality treatment and discusses briefly the prognostic parameters and treatment modalities. Only few studies have discussed about scapular chondrosarcoma and more studies with larger number of patients are needed to develop an evidence-based treatment and follow-up protocol for these patients.

Malignant rhabdoid tumour of liver: Conundrum on ascitic fluid.

Ascitic fluid analysis is an important tool for diagnosis and staging. Cytological analysis is routinely done as a part of workup for ascites. This is challenging in paediatric malignancies where multiple differentials need to be considered at times with limited cellularity. We present a case of malignant rhabdoid tumour of liver in a young child presenting with abdominal lump and ascites. The diagnosis was offered on ascitic fluid cytology based on cytomorphology, supporting immunohistochemistry and later confirmed on biopsy. This report briefly discusses its differentials and approach to diagnosis.

Atypical presentations of fungal osteomyelitis during post COVID-19 outbreak - Case series.

Introduction: Mucormycosis and Aspergillosis are opportunistic fungal infections causing significant morbidity and mortality. Post the outbreak of COVID-19, these fungal osteomyelitis have seen a global rise with few atypical presentations noted. Case report: Current case series reports three such atypical presentations of fungal osteomyelitis including mandibular fungal osteomyelitis in two patients, fungal osteomyelitis mimicking space infection in a middle aged male, and suspected mixed fungal osteomyelitis involving maxillary sinus. Aggressive surgical debridement was indicated along with institution of antifungal therapy (Liposomal Amphotericin B, and Posaconazole). The fungal osteomyelitis was successfully treated with surgical and medical management with no recurrence. Discussion: The injudicious use of corticosteroids in COVID-19 patients along with their immunocompromised status increases their susceptibility to opportunistic fungal osteomyelitis. Prompt and aggressive surgical intervention along with antifungal therapy is important after diagnosing fungal osteomyelitis, as a delay could increase the mortality rate considerably.

Infantile Inflammatory Myofibroblastic Tumor of Spleen.

Background: Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm with unknown etiology and recurrent potential. They are widely reported in children and young adults. Nearly 50% of inflammatory myofibroblastic tumor harbor rearrangement in anaplastic lymphoma kinase (ALK) gene with the majority expressing ALK protein. ALK-negative IMTs harbor alteration in ROS1 gene in a subset of cases. Few reports have shown association of IMT with Epstein-Barr virus (EBV). Case report: We report a case of IMT of the spleen in an 18-month-old infant presenting with abdominal distention and failure to thrive. Workup for ALK-1, ROS1, and EBV small-encoded RNA in-situ hybridization using immunohistochemistry was negative. Conclusions: IMT can arise in an infant spleen.

Screening Strategy for Detecting Double-Hit Lymphoma in a Resource-Limited Setting.

AIM: High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements [double-hit lymphomas (DHL)] are aggressive lymphomas. Current literature recommends fluorescent in-situ hybridization analysis (FISH) in all cases of diffuse large B-cell lymphoma (DLBCL) to identify cases of DHL. However, this approach is not feasible in a resource-limited setting. We analyzed cases of de novo high-grade B-cell non-Hodgkin lymphoma using histomorphology, immunohistochemistry and FISH to identify which cases need to undergo FISH testing in a resource-limited setting. MATERIALS AND METHODS: Cases of de novo high-grade B-cell non-Hodgkin lymphoma that included DLBCL, not otherwise specified and B-cell lymphoma unclassifiable (BCLU) with features intermediate between DLBCL and Burkitt lymphoma diagnosed over a period of 5 years were analyzed by Hans algorithm, MYC, BCL2, and Ki67. MYC, BCL2, and BCL6 break apart FISH was tested in selected cases. RESULTS: One hundred and nine cases were obtained, of which 102 had DLBCL morphology and 7 had BCLU/blastoid morphology. BCL2 expression was noted in 48 cases (44%), MYC in 33 cases (30.3%) and MYC/BCL2 co-expression in 24 cases (22%). FISH testing could be done in 42 consecutive cases, of which 5 cases had MYC and BCL2 co-rearrangement (11.9%) (double-hit) and 2 cases showed rearrangement for only MYC (4.7%) (single-hit). Single-hit lymphoma/DHL showed significant independent positive correlation with BCLU/blastoid morphology, CD10 expression, germinal center B-cell phenotype, and MYC/BCL2 co-expression. The sensitivity and specificity of each parameters include BCLU/blastoid morphology (42% vs. 94%), CD10 positive (50% vs. 88%), germinal center B-cell phenotype (57% vs. 82%), MYC/BCL2 co-expression (85% vs. 80%). Selected candidates for FISH (any one of the above parameters) using this strategy showed a sensitivity and specificity of 100% and 68%, respectively (P=0.001). CONCLUSION: We propose a highly sensitive screening strategy for detection of MYC/BCL2 rearrangement in high-grade B-cell lymphoma in a resource-limited setting (pending validation in a larger cohort).

Eosinophilic Solid and Cystic Renal Cell Carcinoma: From Unclassified to Classified, A Case Report.

Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a novel tumour with unique morphological and immunohistochemical features. It is a recently described entity after the 2016 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs and is characterised by a solid cystic tumour composed of polygonal cells with voluminous eosinophilic cytoplasm and CK20 positivity. This tumour has uncertain malignant potential and also has an association with tuberous sclerosis complex (TSC). Sarcomatoid differentiation has not been reported in ESC RCC till now. ESC RCC poses a diagnostic challenge as many eosinophilic/oncocytic renal tumours are included in the differentials. We present a case of ESC RCC with sarcomatoid differentiation in an elderly female without any clinical features of TSC and discuss the differential diagnosis of oncocytic renal tumours.

Atrophic Kidney-Like Lesion - Case Report of A Provisional Entity with Brief Review of Literature.

Atrophic kidney-like lesion is a recently recognized entity, post 2016 World Health Organization Classification of tumors of the urinary system. The behavior of this tumor is not fully known as only a handful of cases with limited follow-up are available. This entity closely mimics thyroid-like follicular carcinoma of the kidney, which has different prognosis. We report a case of incidentally detected atrophic kidney-like lesion in an elderly gentleman who had urothelial carcinoma of the urinary bladder with a brief review of literature. Atrophic kidney-like lesion and urothelial carcinoma of the urinary bladder association has not been reported in the literature.

Calcified Amorphous Tumor of Left Ventricle: A Rare Cardiac Tumor.

Cardiac calcified amorphous tumor (CAT) is a rare, non-neoplastic, intra-cavity cardiac mass. Only a few cases have been described in the literature. A 46-year-old Indian female presented with decompensated heart failure. On echocardiography, 1.9 x 1.7 cm pedunculated mobile mass in the left ventricle attached to the intraventricular septum was seen. On cardiac magnetic resonance imaging (MRI), the lesion was isointense. Histopathology of the excised mass revealed fibrin deposition with eosinophilic amorphous material in the center with the periphery of the lesion showing calcification without any myxomatous tissue. A final diagnosis of CAT of the heart was established. CAT is composed of calcium deposits in the background of amorphous degenerating fibrinous material. It presents as a pedunculated mass in any chamber of the heart with a very high preponderance of distal embolization. Differentiation from calcified atrial myxoma, calcified thrombi, or other cardiac neoplasms is very difficult. Histopathological examination is the mainstay of diagnosis. Treatment is emergency excision to prevent distal embolization. CAT is a rare non-neoplastic tumor, which is mainly a tissue diagnosis after its resection.

Fulminant necrotising amoebic colitis after corticosteroid therapy for severe COVID-19.

Acute fulminant necrotising colitis is an uncommon presentation of amoebiasis, which can be precipitated after corticosteroid therapy. Clinicians treating patients with COVID-19 with corticosteroid therapy should be familiar with this condition to avoid delay in diagnosis. The disease is associated with high mortality, and prompt diagnosis and management are essential for salvaging patients. We report successful management of a patient who developed this complication following administration of steroids for COVID-19.

Course and outcomes of pregnancy in women treated for acromegaly: Discerning a contemporary cohort.

OBJECTIVE: To analyze pregnancy course and outcomes in women treated for acromegaly and compare outcomes based on disease activity at the time of conception. DESIGN: Retrospective study. PATIENTS: Women with acromegaly diagnosed prior to or during pregnancy from 2010 to 2019, representing cases (14 pregnancies in 12 cases), were later stratified based on active (n = 5) or controlled disease (n = 9) at time of conception. Female acromegalic patients over the same period constituted the 'acromegaly cohort' (AC) (n = 75). RESULTS: All cases had macroadenomas with nadir GH of 15.06 ng/ml (IQR 9-30), IGF-I index of 3.04 (1.96-3.82), for which they had undergone pituitary surgery; except two patients diagnosed during pregnancy, who received pharmacotherapy followed by surgery 4 months postpartum. Adjuvant pharmacotherapy was required in 71.4% patients and radiotherapy in 35.7%. Pregnancy occurred at a median of 2 (0.8-5.1) years after surgery and 21.4% required assisted reproduction. All had term delivery with normal APGAR except one case with gestational hypertension, who delivered a preterm baby. None had congenital malformations. Despite higher baseline IGF-I, GH and tumor volume in those with pre-conceptional active acromegaly, materno-fetal outcomes were not different from those with controlled disease (p > 0.05). Similar or greater proportion of cases had normal GH and no residual tumor postpartum, even in those with pre-conceptional active acromegaly. CONCLUSION: The current study showed conducive outcomes of gestation in women treated for acromegaly and no higher rates of pregnancy parameters or complications than non-acromegaly pregnancies in the same population. Active acromegaly does not seem to have an adverse bearing on outcomes.

De novo double-hit B-cell precursor leukemia/lymphoma - an unusual presentation as peritoneal lymphomatosis.

Peritoneal lymphomatosis (PL) is a rare presentation of extranodal precursor leukemia/lymphoma. The presentation is often non-specific, leading to delayed diagnosis and treatment. In this case, though the preliminary diagnosis was established on ascitic fluid cytology, the disease progressed rapidly, leading to demise before initiating chemotherapy. Immunophenotyping and molecular studies, performed later, established a diagnosis of de novo B-cell precursor leukemia/lymphoma with MYC, BCL2 rearrangements (Double-hit lymphoma). MYC, BCL2 rearrangements are rarely reported in precursor B-lymphoma/leukemia which carry dismal prognosis. In this report, we illustrate autopsy findings of PL in an elderly gentleman who presented with ascites for evaluation.