Biological tailoring of adjuvant radiotherapy in head and neck and oral malignancies – The potential role of p53 and eIF4E as predictive parameters

BACKGROUND: Recent advances in radiation technology has allowed to significantly reduce toxicity and improve the efficacy of radical radiotherapy in head and neck and oral squamous cell cancers. Insights into molecular biology of carcinogenesis has opened a window for identifying aggressive clinical situations that may benefit with larger clinical target volume (CTV ) margin, broader levels of nodal coverage, or alternative radiation sensitizers. AIM: To evaluate the potential role of eukaryotic translation initiation factor 4E (elF4E) and p53 as predictive biomarkers in resected margins of head and neck and oral cancers. MATERIAL AND METHODS: Forty patients with oral cancers and 26 patients with head and neck cancers were evaluated for p53 and eIF4E in their negative surgical margins, for pattern of distribution and outcome. RESULTS: In oral cancers, 27 patients (67.5%) were positive for p53 and 10 (25%) for eIF4E in surgically negative margins. For head and neck cancer, the values were 13 (50%) for p53 and 9 (34.6%) for eIF4E. Twelve patients with oral cancers and 8 patients with head and neck cancers had local failure or death. The association with these biomarkers did not achieve statistical significance. However, adjuvant radiotherapy had a significant protective value. It improved median survival from 15 to 21 months in patients positive for p53 (P = 0.018) and from 12 to 20 months (P = 0.03) in those with eIF4E. There was no predictive association of subsite, tumor size, or nodal status. CONCLUSION: The overexpression of p53 and eIF4E in pathologically negative margins may represent a subset of patients who would benefit from early initiation of adjuvant radiation and tailored intensity-modulated radiotherapy (IMRT).

Histological diversity and clinical characteristics of Ewing sarcoma family of tumors in children: A series from a tertiary care center in South India.

BACKGROUND: The Ewing sarcoma family of tumors (ESFT) are aggressive malignant tumors with small round cell morphology affecting mainly children and adolescents. The aim of this study is to classify the histological diversity and clinical characteristics of ESFT in children from a Tertiary Care Center in South India. MATERIALS AND METHODS: This retrospective descriptive study includes 51 cases of ES in children aged below 15 years. Clinical details were collected from case files. Histomorphological features were reviewed and tumors were subtyped into classic, primitive neuroectodermal tumor (PNET) and atypical variants along with immunohistochemical markers, cytogenetics, and fluorescence in situ hybridization (FISH). RESULTS: Fifty‑three percent were female and 47% were male with mean age of 10 years. The most common site of involvement was skeletal involvement in 71%, followed by soft tissue involvement in 23%, and visceral involvement in 6%. Localized disease at presentation was seen in 44%, locally advanced disease in 28%, and metastatic disease in 28%. Recurrence was documented during follow‑up in 18% of the cases. Histomorphologically, classic type was the most common (72%) followed by PNET (20%) category and atypical variant (8%). All cases were immunoreactive for CD99. Cytogenetic study in 12 cases showed translocation t(11;22) (q24;12) in 80% and variant translocations such as t(3;16), t(3;11) with nonspecific numerical abnormalities in 20%. FISH was carried out for documentation of four cases with atypical histomorphology. CONCLUSION: ESFT had wide histological variation which required confirmation by ancillary studies.

Immunohistochemical analysis of CK 18 in dental follicles of impacted third molars: A pilot study.

Objective: Odontogenic tumors are lesions derived from epithelial, ectomesenchymal, and/or mesenchymal elements that still are, or have been, part of the tooth-forming apparatus. Approximately 80% of odontogenic tumors occur in the mandible, with a marked predilection for the posterior region, and are often associated with an unerupted tooth. The aim of this study was to determine whether cytokeratin (CK) 18 immunostaining decorated the follicular tissue removed at the time of prophylactic extraction of impacted mandibular third molars, which might suggest oncofetal transformation. Materials and Methods : Fifty-four impactions met the study inclusion criteria, of which 24 cases showed the presence of reduced enamel epithelium and/or connective tissue with odontogenic epithelium, which were subjected to CK 18 immunostaining. Results: All 24 cases with adequate epithelium were CK 18 immunonegative. Conclusion: There was no oncofetal transformation in the odontogenic epithelia of the dental follicles studied. Thus, although we reaffirm that evaluation of follicular tissue is imperative since disease conditions may be found in minute follicular spaces, development of odontogenic cysts and tumors is unlikely.

Ovarian hemangioma with stromal luteinization and HCG-producing mononucleate and multinucleate cells of uncertain histogenesis: A rare co-existence with therapeutic dilemma.

A 21 year old female presented with amenorrhea, hirsutism and change in voice along with an elevated serum β-HCG (human chorionic gonadotrophin) level and normal CA-125 level. Laparotomy revealed an enlarged right ovary measuring 6 × 5 × 1 cms with presence of an ovarian hemangioma along with stromal luteinization and HCG producing mononucleate as well as multinucleate cells of uncertain histogenesis on histopathological examination. Immunohistochemistry for inhibin and calretinin were positive in the luteinized component whereas β-HCG and Ki-67 were positive in the multinucleate cell component. The diagnostic rarity and therapeutic dilemma of such a rare mixed tumor within a single ovary has proven to be an exceptional case and an excellent investigative opportunity.

Childhood hepatic angiosarcoma--a case report.

Hepatic angiosarcoma (HAS) is an extremely rare liver tumor in children. We report a case of childhood HAS in a six year old girl who presented with acute abdominal pain and fever with a mass in epigastrium. Left hepatic lobectomy was performed with a clinical diagnosis of hepatoblastoma. Histopathological examination revealed features typical of hepatic angiosarcoma. The case is presented for its rarity and to discuss the interrelation between infantile hemangioendothelioma (IHE) and HAS.

Follicular dendritic cell tumour--a case report.

Follicular dendritic cell tumors are rare entities, which are however being increasingly recognised. One such tumor in the parapharyngeal region, diagnostically challenging, and with an unusual histological feature is reported, with a short review of the literature.

Sinus histiocytosis with nodal and extranodal involvement--a case report.

A two and half years old male child of sinus histiocytosis with massive lymphadenopathy, paraplegia and spinal cord involvement was treated with surgery and radiotherapy for the spinal cord compression and later with chemotherapy for his nodal disease in the neck. There was a significant improvement in his neurologic status as well as in his nodal status reiterating the role of combination therapy in this disease.