A Clinicopathological Study with Risk-Stratified Staging of Pediatric Hepatoblastoma: A 5-Year Experience from a Tertiary Cancer Center.

Background & Objective: Hepatoblastoma encompasses 1% of pediatric malignancies and is the most common liver malignancy in children. Ninety percent of cases are younger than 5 years of age. Clinical and pathological risk stratification forms a crucial role in determining the treatment strategy. This study aimed to assess the clinicopathological profile of hepatoblastoma with risk stratification and follow-up in children. Methods: A retrospective evaluation was performed on all pediatric patients diagnosed as hepatoblastoma between 2016 and 2020 in our institution. Clinical, radiological, biochemical, pathological, and treatment data were analyzed. Cases were stratified based on the SIOPEL protocol and compared with the outcome. Results: The median age of all children was 1 year, the male-to-female ratio was 2.3:1, and elevated α-fetoprotein (AFP) was observed in all cases. SIOPEL risk stratification showed that 50% of children were at high risk. The histopathological types were fetal (30%), embryonal (20%), and macrotrabecular (5%) patterns under epithelial type and mixed epithelial and mesenchymal type (45%) with 1 case showing teratoid features. During the follow-up period, 6 out of the 7 children who died, belonged to the high-risk SIOPEL category, and 5 presented a mixed epithelial and mesenchymal pattern. Conclusion: Our study found a significant correlation between clinicopathological data, histopathological patterns, and outcomes. Accordingly, histopathological patterns could be considered one of the criteria for risk stratification. Histopathological risk stratification indicators (such as SIOPEL and PRETEXT) have strong prognostic and predictive outcomes; hence, our study emphasizes such parameters to aid oncologists.

Neuroblastoma in uncommon age group - A case series diagnosed on cytology.

BACKGROUND: Neuroblastoma is the most common extracranial malignant neoplasm in early childhood. It is rare in the adult population. AIMS AND OBJECTIVES: We aimed to study the incidence of neuroblastoma in the uncommon age group diagnosed on cytology. MATERIALS AND METHODS: A prospective descriptive study spanning 2 years from December 2020 to January 2022 was done, in which neuroblastoma cases diagnosed by Fine needle aspiration cytology aged >12 years were collected. The clinical, cytomorphological and immunohistochemical findings were studied. Histopathological correlation was done wherever available. RESULTS: We identified three cases of neuroblastoma during this period. Two cases were middle-aged adults, and one was an adolescent. All cases presented with abdominal masses and revealed small round cell tumor on cytology. Two cases fell into undifferentiated category and one case fell into the poorly differentiated subtype. All cases were positive for neuroendocrine markers. Histopathological correlation was available in two cases. MYC N amplification was absent in all cases. CONCLUSION: It differs from pediatric neuroblastoma due to the lack of classical histomorphological features and molecular alterations. Adult-onset neuroblastomas carry a worse prognosis than childhood tumors.

Angiomatoid Fibrous Histiocytoma, A Great Mimicker -A Short Series of 3 Cases with EWSR1 Fusion.

Angiomatoid Fibrous histiocytoma (AFH) is a rare soft tissue neoplasm that is often misdiagnosed initially. It is commonly encountered in the superficial extremities of children and young adults. It is composed of a nodular proliferation of bland looking spindled to ovoid cells, some with variant histology and characterized by EWSR1 fusion. We, herein, present three such cases, who presented with swelling in the right leg (case 1), right forearm (case 2), and right thigh (case 3). Case 2 presented in the fourth decade with a large swelling compared to the other two cases that presented in 3rd decade with a small swelling. Histologic examination of case 2 showed extensive myxoid changes making it diagnostically challenging. All three cases showed EWSR1 fusion with a break-apart probe. Follow-up was uneventful in all three cases. AFH, although it is a benign neoplasm, is a great mimicker of various low-grade spindle cell sarcomas. Awareness of this entity with its various histomorphological variants is necessary to accurately diagnose this lesion.

Diagnosis of solid tumors in infants by fine-needle aspiration cytology: 5 years retrospective study from a tertiary care oncology center in South India.

INTRODUCTION: Neuroblastoma (NB), Wilms tumor (WT), hepatoblastoma (HBL), germ cell tumors (GCT), rhabdomyosarcoma (RMS), and so forth are the commonly identified solid tumors in infants. Invasive diagnostic techniques are more challenging in infants than older children. fine needle aspiration cytology (FNAC) is a safe, minimally invasive and outpatient procedure which is time and cost-effective for solid tumor diagnosis. This study aims to evaluate the role of FNAC in the diagnosis of various infantile solid tumors. METHODS: In this retrospective study, 61 cases of FNA of infant solid tumors were retrieved from the cytology archives over a period of 5 years from January 2013 to December 2017. Cytomorphology was studied and immunohistochemistry on cell block was performed wherever feasible. Histopathological correlation was done in 19 cases. RESULTS: Of the 61 cases studied, 60 cases were included in the study of which 35 were male and 25 were female. Infantile solid tumors constituted 7.3% of all pediatric solid tumors reported in cytopathology division of our Institute. The most common final diagnosis was NB (15, 25%) followed by HBL (13, 21.6%), WT (10, 16.6%), RMS (nine, 15%) and GCT (nine, 15%). The commonest site was abdominal-pelvic (42, 70%). A definitive independent diagnosis could be made on FNA in 48 cases (80%). Follow-up was done for 1.5 to 4 years (mean 26 months). The highest and lowest mortality was noted in NB (64.3%) and WT (12.5%) respectively. CONCLUSION: This study concludes that FNAC can be adopted as a diagnostic modality in infant solid tumors.

Cytomorphological and immunohistochemical features of renal and extrarenal rhabdoid tumors.

BACKGROUND: Rhabdoid tumors are rare, highly lethal neoplasms characterized by alterations of SMARCB1 gene in chromosome 22, which occurs in infants and children. Fine needle aspiration (FNA) is an effective technique to diagnose this tumor when combined with Immunohistochemistry (IHC) and molecular genetics. In this study, we describe four cases of renal and extra-renal rhabdoid tumor of which three cases were diagnosed on FNA with IHC. MATERIALS AND METHODS: The study includes four children with renal and extrarenal rhabdoid tumor retrieved from cytology archives. FNA was done with cell block, IHC, and cytogenetics. The cytomorphology with ancillary studies were reviewed along with histopathology which was available in 3 out of 4 cases. RESULTS: All the four cases had similar cytomorphologic features comprising of large cells having vesicular nuclei which can be central or eccentric with prominent nucleoli and abundant pale cytoplasm. Few cells had intracytoplasmic hyaline inclusion. Cell block with IHC confirmed the diagnosis in three cases. One case in which cell block could not be made the diagnosis was confirmed on biopsy with IHC. CONCLUSION: Rhabdoid tumors are uncommon but aggressive neoplasms with poor prognosis. Our study highlights that they can be diagnosed accurately on FNA cytomorphology when combined with IHC on cell block.

Primary Gastric Synovial Sarcoma in a Child: A Case Report and Review of the Literature.

Synovial sarcoma is a mesenchymal neoplasm that shows a specific t(X;18) translocation that leads to the formation of SS18-SSX gene fusions and is most commonly seen in soft tissues of the extremity. The gastrointestinal tract is a very rare site of involvement. We report a case of primary gastric synovial sarcoma in a 13-year-old male child. Synovial sarcoma should be included in the differential diagnosis when spindle cell neoplasms are encountered in the stomach. A high degree of suspicion, followed by the necessary immunohistochemistry and molecular studies, is required to make an accurate diagnosis.

Primary Ewing sarcoma of the lung diagnosed on cytology: Case report with review of literature.

Primary Ewing sarcoma (ES) of the lung is anecdotally rare, with few cases reported in literature. This report describes a 46 year-old man who presented with cough and chest pain. CT Thorax revealed a lesion in the right lung. Ultrasound guided fine-needle aspiration of the mass and subsequent cytologic examination exhibited a small round cell morphology. Immunohistochemistry done on the cell block revealed CD 99 and FLI-1 positivity, confirming the diagnosis of ES. FISH supported the diagnosis, showing the EWSR1 rearrangement. Radiologic investigations ruled out a primary tumour elsewhere, confirming the diagnosis of primary pulmonary ES. The patient was started on chemotherapy.

Dickkopf Homolog 3 (DKK3) Acts as a Potential Tumor Suppressor in Gallbladder Cancer.

Gallbladder cancer (GBC) is a common malignancy of biliary tract cancers and its incidence has been rising rapidly worldwide. The prognosis for this disease is dismal as most of the symptoms are non-specific leading to a definitive diagnosis only at a late stage. Loss of DKK3 gene is associated with a possible tumor suppressor role in human cancers. The role and regulation of DKK3 in GBC have not been studied. We found that DKK3 expression levels were low in GBC patients and cell lines. Treatment of GBC cell lines with demethylating agent 5-Aza- 2'-deoxycytidine enhances its expression, establishing impact of methylation on DKK3 expression. We observed low expression of DKK3 in gallbladder adenocarcinoma tumors and highly invasive GBC cell lines. We showed that overexpression of DKK3 can decrease cell invasion, proliferation, and colony forming ability of GBC cells. Our data thus demonstrated the DKK3 gene is a potential tumor suppressor gene in GBC and aberrant promoter methylation could be involved in its downregulation, which may play a role in the tumorigenesis and aggressiveness of GBC.

A rare case of primary synovial sarcoma of lung.

Synovial sarcoma of lung is a very rare tumor accounting for 0.5% of all primary lung malignancy. It presents clinically with cough, chest pain, shortness of breath, or hemoptysis, with a mass lesion on X-ray and computerized tomography scan. Diagnosis is made by histopathology and immunohistochemistry. Here, we report a case of 48-year-old male, who presented with right-sided chest pain, cough with blood-tinged sputum, and found to have primary pulmonary synovial sarcoma of lung.

Malignant phyllodes tumor with heterologous differentiation: A rare case report.

Sarcomas of the breast are rare neoplasms accounting for less than 1% of breast malignancy. A 40-year-old-female with left breast mass underwent wide-excision and on histopathological examination a diagnosis of malignant phyllodes tumor with heterologous differentiation of osteosarcoma and chondrosarcoma was rendered. The heterologous elements were tumor osteoid formation and tumor chondroid formation. The rarity of the lesion was considered for reporting and on follow-up the patient was free of metastasis.

Screening for EGFR mutations in lung cancer, a report from India.

Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers including the lung malignancy. Genetic modifications such as deletions, insertions and Single Nucleotide Polymorphisms in the tyrosine kinase (TK) domain of EGFR is a common feature observed in most lung cancers. Gefitinib and erlotinib are commonly available therapeutic drugs which act as specific inhibitors for the tyrosine kinase domain of EGFR and associated with EGFR mutations in exons 18-21. However the prevalence of mutation varies among ethnicity, grade, age and gender. This is the first report on the prevalence of EGFR mutation in non-small cell lung cancer patients using DNA obtained from samples such as biopsy/cytology/pleural fluid and Fine Needle Aspiration (FNA), across India. We have screened for 29 somatic mutations which span exons 18, 19, 20 and 21 of EGFR gene using Scorpion probe based ARMS-PCR technique. DNA from 220 NSCLC tissue samples were analyzed for EGFR mutations and mutations were detected in 51.8% of the study population. Among the mutant positive cases, the deletions in exon 19 (52%) and a missense mutation L858R in exon 21 (26%) were most predominant. There was a significant increase in overall mutations (p=0.01) as a function of age, mutation in exons 19 and 21 together (p=0.003), mutations in exons 18, 19 and 21 (p=0.04) and mutations in exons 18 and 19 (p=0.03) in females. Mutations did not seem to significantly correlate metastases or disease progression. Mutations in exons [19] and 21 together were significant in non-smokers compared to smokers (p=0.01) using Mann-Whitney tests. The study suggests high prevalence of EGFR positivity in NSCLC in Indian sub-population and provides opportunities for targeted therapies for this group.