Pediatric Colorectal Carcinoma: A Series of Seven Cases.

Introduction: Colorectal carcinoma (CRC) accounts for <1% of all the neoplasms of children. Unfavorable histology and delayed diagnosis often result in poor outcome. This study aimed to investigate the clinical characteristic and prognosis of pediatric patients with CRC. Materials and Methods: A retrospective review of medical records of all patients diagnosed of CRC between 2015 and 2020 was performed. Data regarding gender, age, location, and histopathology were collected. Results: Seven children (5 males and 2 females) were included in the study. Age ranged between 8.6 and 11.8 years. Abdominal pain was the most common symptom. The duration between onset of symptoms to the diagnosis ranged from 5 days to 8 months. Right-sided tumors were more common than the left side. Histopathological examination showed mucinous adenocarcinoma in four/seven patients and signet cell variant was seen in 2/7. Immunohistochemistry was positive for cytokeratin and beta-catenin, however, all microsatellite instability markers were found negative. Despite surgical treatment and chemotherapy, four of our cases faced mortality and one patient was lost to follow-up. Conclusion: CRC can present in first decade of life and often misdiagnosed. Pediatric CRC has distinct tumor biology and shares a poor prognosis. Paucity of literature from the Indian subcontinent should urge further clinicopathological trials for establishing etiology and for refining treatment recommendations in these children.

Meckel Gruber and Joubert Syndrome Diagnosed Prenatally: Allelism between the Two Ciliopathies, Complexities of Mutation Types and Digenic Inheritance.

Background: Antenatally detected occipital encephalocele and polycystic kidneys are a common presentation of ciliopathies like Joubert syndrome and Meckel Gruber syndrome which have considerable genetic and phenotypic overlap. Case reports: We describe 3 cases of antenatally diagnosed occipital encephalocele and enlarged kidneys with fetal autopsy, histopathology & exome sequencing results. A novel nonsense variant in the CEP290 gene was reported in first case (Meckel syndrome). The second case shows the importance of fetal exome where the parents were carriers for 2 ciliopathy genes (TMEM138 & SDCCAG8). Diagnosis in this case was confirmed by fetal exome sequencing (Joubert syndrome). Multiexon deletion in TMEM67 and KIF14 present in trans was identified in the third case (Meckel syndrome), likely resulting in digenic inheritance. Conclusion: We report 2 cases of Meckel syndrome with a novel variant and multiexon deletion, and 1 case of Joubert syndrome which depicts the limitations of preconceptional carrier screening in ciliopathies due to overlapping phenotypes.

Diagnostic Relevance of GATA 3 Expression in Urinary Bladder Carcinoma of Divergent Differentiation and Other Histological Variants.

GATA binding protein 3, a zinc finger transcription factor, has now been demonstrated as a valuable and sensitive marker for conventional urothelial carcinoma with sparse literature related to its expression in various histological variants. It is a prospective study where 74 consecutive cases of bladder carcinoma were included between August 2016 and January 2017 followed by immunohistochemistry to assess GATA 3 expression in conventional as well as different urothelial carcinoma (UC) variants. Overall, 57 of the 74 lesions (77%) demonstrated nuclear staining for GATA 3. GATA 3 expression significantly correlated with histological grade (P < 0.001) and muscle invasion (P = 0.005). Divergent differentiation was observed in 54% (40/74) of the total cases. The study included 12 different variants of urothelial carcinoma. All or majority of the cases of clear cell (6/6, 100%), glandular (6/8, 75%), and sarcomatoid (4/6, 66.7%) variants expressed GATA 3 in a moderate to strong fashion and belonged to group III or IV. Nested variant, small cell carcinoma, pure squamous cell carcinoma, and squamous component of urothelial carcinoma with squamous differentiation do not show any GATA 3 expression. GATA 3 was expressed more intensely as well as in greater number of tumor cells at lymph node metastatic tumor deposits as compared to the primary tumor. GATA 3 expression was not significantly associated with tumor stage or patients' clinical outcomes. GATA 3 is expressed in majority of variants of UC albeit with variable staining; however, situation is challenging in some variants known to be associated with poor prognosis like nested variant, small cell carcinoma, and squamous cell carcinoma where it is not expressed. Hence, the sensitivity of this determinant is diminished in these variants, which may affect the interpretation of GATA 3 stains at metastatic sites as well as their distinction from secondary bladder involvement, by tumors of non-urothelial origin.

Non-malignant fibroblastic/myofibroblastic tumors in pediatric age group: Clues and pitfalls to the cytological diagnosis.

INTRODUCTION: Fibroblastic/myofibroblastic tumors constitute 12% of all pediatric soft tissue tumors with the majority of them belonging to the benign and intermediate prognostic categories. They are often misdiagnosed owing to their variable clinical presentation and unusual microscopic features. The diagnosis, specially cytological diagnosis of benign and intermediate categories is difficult due to paucity of cellular component and increased amount of extracellular matrix as compared to malignant ones. We hereby discuss the Fine needle aspiration cytology (FNAC) findings of non-malignant fibroblastic/myofibroblastic lesion in the pediatric age group encountered at our institute. METHODS: All the benign and intermediate fibroblastic/myofibroblastic/fibroadipocytic lesions (age 0-12 years) diagnosed on FNAC over a period of 3½ years (Jan 2016- July 2019), with availability of corresponding histopathology were included in the study. RESULTS: A total of seven pediatric benign and intermediate fibroblastic/myofibroblastic lesions with histopathological confirmation were identified which included Infantile digital fibromatosis (IDF) (n = 2), Lipofibromatosis (n = 1), Fibrous hamartoma of infancy (FHI) (n = 1), Fibromatosis colli (FC) (n = 2) and myofibroma/myofibromatosis (n = 1). FNAC smears were mainly paucicellular with presence of benign spindle shaped cells in a collagenous stroma common to almost all the cases. A few additional findings such as degenerated skeletal muscle fibres, muscle giant cells and mature adipose tissue were also present in some cases. CONCLUSION: Fibroblastic/myofibroblastic tumors although uncommon, form an important category that must be considered in the differential diagnosis of pediatric soft tissue tumors. FNAC cytology features when assessed in a proper clinical setting (specially the age and site of presentation) are helpful in suggesting probable preoperative diagnosis in these lesions.

Diagnostic utility of GATA3 immunohistochemical expression in urothelial carcinoma.

AIMS: This study aims to explore the utility of GATA binding protein 3, a zinc finger transcription factor, expression in genitourinary carcinoma, especially urothelial carcinoma. SETTINGS AND DESIGN: It is a prospective study where 74 consecutive cases of urothelial carcinoma along with 10 cases each of prostatic adenocarcinoma (PC) and conventional clear cell renal cell carcinoma were included between August 2016 and January 2017. METHODS AND MATERIALS: All the cases were histopathologically evaluated and immunohistochemically stained for GATA binding protein 3. Only nuclear positivity was considered as positive. Immunoreactivity score for GATA expression was calculated based on the staining intensity as well as percentage. STATISTICAL ANALYSIS USED: The statistical analysis was done using Statistical Package for Social Sciences Version 15.0 statistical analysis software. P value of <0.05 was considered statistically significance. RESULTS: GATA3 expressions were seen in 77% of the cases of urothelial carcinoma, whereas none of the clear cell renal cell carcinoma and prostatic adenocarcinoma cases was GATA3 positive. GATA3 expression significantly correlated with histological grade and muscle invasion with a weaker or negative expression in high-grade muscle invasive tumor as compared to low-grade and noninvasive neoplasm. Significantly weaker expression of GATA3 was found in cases with severe nuclear pleomorphism, mitosis >10/10 hpf, presence of necrosis, and tumor-infiltrating lymphocytes. No significant change in the status of GATA3 expression was seen in follow-up cases between initial Transurethral resection of bladder tumor (TURBT) and post-recurrence TURBT or radical cystectomy specimens. CONCLUSIONS: GATA3 as a sensitive and specific marker for urothelial carcinoma can be effectively used to exclude other genitourinary malignancies, PC, and renal cell carcinoma, at metastatic site. This marker can also be effectively used in predicting the probable grade and invasion in biopsy material with poor morphological characteristics, thereby helping in appropriate management in such cases.