Naseem Akhtar

Do Human Papilloma Viruses Play Any Role in Oral Squamous Cell Carcinoma in North Indians

BACKGROUND Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy among males in India. While tobacco and alcohol are main aetiological factors, human papilloma virus (HPV) presence has surprisingly increased in head and neck Squamous Cell Carcinoma (HNSCC) in the past two decade but its frequency in OSCCS is still uncertain. We aim to explore the frequency of HPV and its major genotypes in North Indian patients and their association with clinicopathological and histopathological features and p16 expression pattern. MATERIALS AND METHODS The study group comprised 250 histologically proven cases of OSCC. HPV was detected by real time PCR in tumor biopsy specimens and confirmed by conventional PCR with PGMY09/ PGMY11 primers. Genotyping for high-risk types 16/ 18 was conducted by type specific PCR. p16 expression was assessed by immunohistochemsitry. RESULTS HPV presence was confirmed in 23/250 (9.2%) OSCC cases, of which 30.4% had HPV 16 infection, 17.4%were positive for HPV 18 and 26.1% had co-infections. HPV presence was significantly associated with male gender (p=0.02) and habit of pan masala chewing (p=0.01). HPV positive cases also had a history of tobacco consumption in 91.3% cases. p16 over expression was observed in 39.1% of HPV positive cases but this was not significantly different from negative cases (p=0.54). CONCLUSIONS The frequency of HPV in OSCC is low in North-India and majority of cases are associated with a tobacco habit. It appears that tobacco shows a confounding effect in HPV positive cases and use of p16 protein as a reliable marker to assess the potential etiological role of HPV in OSCC in our population is not suggested.

Cancers of upper gingivobuccal sulcus, hard palate and maxilla: A tertiary care centre study in North India.

Introduction: Oral cancer is the sixth most common malignancy in the world, and the third most common in southeast Asia. Cancers of the upper gingivo-buccal complex are uncommon and reported infrequently. In this article, we have assessed the clinicopathological features of such cancers and their optimal management. Materials and Methods: We studied 64 patients with cancer of the upper gingivobuccal sulcus (GBS), hard palate, and maxilla seen between February 2009 and 2013 over a span of 4 years. Results: Of the 64 patients studied, 45 were male. The mean age at presentation was 50.59 years (24-80 years). Of the 64, 48 patients (75%) had a history of substance abuse in the form of tobacco chewing, smoking or alcohol. On presentation, 48 of the 64 patients (75%) had T4 disease, eight had T3, six had T2 lesion, one had T1 lesion, and 1 patient had a neck recurrence with distant metastatic disease (Tx). Out of the 64 patients, 31 had clinically palpable neck disease and two patients had distant metastatic disease. Of the 64 patients, 58 had squamous cell carcinoma, two had adenoid cystic carcinoma of the hard palate and one patient each had melanoma, sarcoma, neuroendocrine tumor, and mucoepidermoid carcinoma. Following imaging, 18 patients (28.13%) underwent upfront surgery and six following neoadjuvant chemotherapy. 14 of the 24 patients operated had simultaneous neck dissection. 2 patients with distant metastasis and 1 with cavernous sinus thrombosis received palliative chemotherapy. Out of the 64 patients, the other 24 who were inoperable were referred to radiotherapy. Conclusion: Upper GBS, hard palate and maxilla cancers are uncommon and are diagnosed at an advanced stage due to delay in presentation and ignorance of our population. Surgery offers the best form of treatment. NACT may be tried to downstage the disease in selected patients with borderline operable disease. However, generous margins should be taken post chemotherapy with concomitant neck dissection. Adjuvant radiotherapy is recommended in selected patients after surgery.

p16 and p53 in HPV-positive versus HPV-negative oral squamous cell carcinoma: do pathways differ?

BACKGROUND p16 overexpression and wild-type p53 expression are associated with human papilloma virus (HPV) in cervical and oropharyngeal cancer. Role of HPV-related carcinogenesis in the etiology of oral squamous cell carcinoma (OSCC) is still vague in Indian population. We aimed to explore the expression pattern of p16 and p53 in HPV-positive and HPV-negative OSCC to elicit differences, if any. Further their effect on survival of patients was studied. METHODS Thirty-one consecutive HPV-positive as well as 31 age and sex-matched HPV-negative OSCC cases from a case series of 369 histologically diagnosed cases of OSCC were included in this study. HPV was detected by two methods, viz. real-time PCR and conventional PCR in biopsy samples. p16 and p53 protein expression was assessed by immunohistochemistry, and p16 mRNA expression was quantified with real-time PCR using SYBR Green assay. RESULTS p16 was expressed in six (19.4%) HPV-positive and in four (12.9%) HPV-negative cases. Overall mutant-type p53 expression in 62 OSCC cases was 54.8%. Out of ten p16-positive cases, eight expressed mutant-type p53 and only two cases expressed wild-type p53. Risk factors including oral tobacco consumption and alcohol were present in all these ten p16-positive cases. Survival of patients was not affected by HPV, p16 and p53 status. CONCLUSION Presence of mutant-type p53 and exposure to tobacco-related risk factors in both HPV-positive and negative cases suggest existence of p53-related carcinogenesis in HPV-positive cases in Indian population.

Primary malignant melanoma of oral cavity: A tertiary care center experience

Background: Primary mucosal malignant melanoma is an extremely rare, aggressive neoplasm accounting for 0.5% of all oral malignancies. Any pigmented lesion in oral cavity should have an index of suspicion, which should be investigated to detect the disease at an early stage and managed appropriately. Melanomas tend to invade locally into the tissue or metastasize more commonly than other malignant tumors of the oral cavity. Materials and Methods: We report a retrospective case series of eight patients suffering from primary oral malignant melanoma treated in our department between 2012 and 2014. The details were recorded from the departmental computerized database and patients on follow-up. Results: There were six male and two female patients with a mean age of 46.8 years. Hard palate was the most common affected site in oral cavity. Pigmented lesion\ulcer was the most common presenting symptom. Majority of patients (5 patients) were diagnosed with Stage III (distant metastasis), two patients in Stage II, and one patient in Stage I. Three patients were treated with definitive surgery and five patients with palliative chemotherapy in view of distant disease. Following surgery, two of them required adjuvant chemoradiotherapy in view of nodal spread. Patients had a mean follow-up of 10.5 months (range: 8–26 months). Patients treated with definitive surgery had a mean survival rate of 16 months (range: 10–26 months), with local recurrence in one patient. Metastatic melanoma patients treated with palliative chemotherapy had a mean disease control rate of 5 months (range 5–9 months). Conclusion: Oral melanoma carries dismal prognosis with a 5-year survival rate of 5–20%. Early detection of the lesion, proper evaluation, and appropriate treatment are very important to cure the disease.

Adenocarcinoma of Gall Bladder Metastasis to Cervix: a Case Report with Review of Literature

Gallbladder cancer is the most common malignant tumor of the biliary tract. High incidence is observed in Chile, Japan, and northern India. Owing to its non-specific symptoms, gallbladder carcinoma is generally diagnosed at a late stage [1]. Gall bladder cancer is characterized by early adjacent organ invasion, extensive loco-regional lymph node metastasis and vascular and common bile duct involvement and distant metastasis. The liver is most common site of distant metastasis. Other rare metastatic sites described are the lung, ovary, skin, central nervous system, heart, and bone [2]. Metastasis of carcinoma of gall bladder to cervix is extremely rare. To the best of our knowledge, only four such cases have been reported in English literature till date [3–6]. Here, we report a case of carcinoma gallbladder metastasizing to cervix.

Giant Exophytic Renal Angiomyolipoma Mimicking as Retroperitoneal Sarcoma; A Case Report with Review of Literature

A 30-year-old woman was admitted with a 7 month history of dull pain and palpable lump in left side of abdomen. No other significant history noted. Abdominal examination revealed mass in left side of abdomen measuring 25 x 20 cm, extending from left hypochondrium up to pubic symphysis, mass was smooth, firm, non-tender with well defined margins. Hemogram and renal function tests were within normal limits. Contrast-enhanced computed tomography (CECT) of abdomen revealed large well defined mass in left side abdomen with predominance of fat (-69 HU) measuring 23 x 20 x 12cm, extending from epigastrium to pelvis. It also showed multiple enhancing vessels within the lesion and an ill-defined interface with lower pole of left kidney [Table/Fig-1a-d]. Chest X-ray was normal. [Table/Fig-1a-d]: CT Scan revealed large well defined mass in left side of abdomen, extending from epigastrium to pelvis with predominance of fat (-69 HU) measuring 23 x 20 x 12cm With a preoperative diagnosis of retroperitoneal liposarcoma, the patient was planned for exploratory laparotomy. At laparotomy, large bosselated mass was found arising mainly from lower pole of kidney [Table/Fig-2]. No regional or distant metastases were noted. Patient underwent partial nephrectomy with enbloc resection of the mass. Gross examination of the tumor showed a well encapsulated soft tissue mass measuring 30 x 25 x 12 cm and weighed around 8000 grams, with lower pole of kidney identified at its upper aspect [Table/Fig-3]. Histologically, the tumor was made of mature adipose tissue, numerous thick walled poorly organised blood vessels and smooth muscles [Table/Fig-4a&b]. Final diagnosis of angiomyolipoma was made. Patient is disease free at 14 months of follow up. [Table/Fig-2]: Laparotomy revealed large bosselated mass was found arising mainly from lower pole of kidney [Table/Fig-3]: Gross examination of the tumor showed a well encapsulated soft tissue mass measuring 30 x 25 x 12 cm and weighed 8000 grams, with lower pole of kidney identified at its upper aspect (arrow mark) [Table/Fig-4]: Microscopy revealed tumor made of mature adipose tissue, numerous thick walled poorly organised blood vessels and smooth muscles Angiomyolipoma (AML) is an unusual benign neoplasm of kidney composed of variable mixture of fully differentiated smooth muscles and mature adipose tissue. It accounts for 0.3% to 3% of all renal tumors [1]. The first case of “Angiomyolipoma” was originally described by Fischer in 1911 and term “Angiomyolipoma” was coined by Morgan in 1951. Initially, AML was considered to be a form of hamartoma or choristoma. Recent evidence suggests AML to be of monoclonal origin, possibly derived from perivascular epitheloid cells. Tumor shows strong positivity for estrogen and androgen receptor suggesting strong hormonal influence in its aetiology. Majority of AMLs occur in females and are rare before puberty. AMLs can occur sporadically or in association with tuberous sclerosis, which accounts for 45 to 80% of cases. Typical sporadic AML is usually unilateral, asymptomatic and an incidental finding. Majority of sporadic AML occur in middle aged women (4th or 5th decade) [2]. Tuberous sclerosis associated AML is seen in younger age (mean age is 30 years), multiple, bilateral, less female to male predominance and are usually symptomatic. Occasionally, AML have unusual extrarenal occurrence and is reported in hilar lymph nodes, retroperitoneum, liver and direct extension into venous system. Around 25% of AML’s have predominantly exophytic growth, extending extrarenally into perirenal spaces. Majority of patients were asymptomatic. Classical presentation includes flank pain, palpable mass and gross hematuria. Most important complication of AML is massive retroperitoneal haemorrhage (known as Wunderlich syndrome), noted in up to 10% of patients. The Wunderlichs syndrome is clinically characterized by the Lenks triad which are acute flank pain, a flank mass and hypovolemic shock [3]. AML have a benign clinical course, with slow growth pattern and lack of distant metastasis. Most AMLs are incidental finding on imaging and may resemble malignancy. Ultrasonography (USG) reveals a well circumscribed, hyperechogenic lesion with shadowing effect are classical findings that help to differentiate from renal cell carcinoma. AML appears to be diagnosed accurately on CECT scan by presence of fat within a renal lesion (confirmed by a value of –20 to -80 HU on imaging) [4]. About 5% of AMLs do not show the fat attenuation on imaging and hence cannot be differentiated from renal cell carcinoma [4]. Angiography may show aneurysmal dilatation in 50% of AML and the size of aneurysm correlates with increased risk of rupture. Despite characteristic radiologic findings of AML, diagnosis can be confused in following three conditions: liposarcoma, fat poor AML resembling renal cell carcinoma and possibility of fat containing renal cell carcinoma. Giant exophytic AML may resemble a retroperitoneal sarcoma. It may be difficult to distinguish exophytic AML from a well differentiated liposarcoma, as both are fat containing tumours’ and have similar appearances on imaging. Liposarcomas usually compress or extrinsically push the renal parenchyma whereas AML may cause a small indentation of the renal parenchyma and presence of enlarged vessels. Strong positivity for HMB-45, a monoclonal antibody is highly characteristic of AML and can be used to differentiate it from sarcoma. Surgical treatment includes tumour excision with or without nephrectomy, nephron sparing surgery or arterial embolisation based on tumor size, extent and its clinical presentation. Role of ablative therapies such as radiofrequency ablation and cryoablation is not well established and might be considered in multicenteric tumors or elderly patients with comorbidities. AML is a rare benign neoplasm arising from perivascular epitheloid cells. Majority of AMLs are asymptomatic and can occur in association with or without tuberous sclerosis. These are detected incidentally on imaging and demonstration of fat within the tumour by computed tomographic imaging (-20 to -80 HU units) is thought to confirm the diagnosis of AML. Diagnosis of exophytic AML should always be considered before making a diagnosis of retroperitoneal liposarcoma, as they have similar radiologic features but differ in prognostic value and treatment approach.

Prognostic significance of AgNOR Proliferative Index in gallbladder carcinoma - A potential alternative to frozen section analysis

Introduction: Number of Argyrophillic Nucleolar Organizer Regions (AgNORs) is a good indicator of cellular proliferation activity and is useful diagnostic tool to estimate the malignant potential of tumors. Methods: Tissue sections from 40 cases of gall bladder disease, including 27 cases of gallbladder carcinoma and 13 cases of chronic cholecystitis, were studied for AgNORs count. The correlation of the AgNOR was carried out with various clinco-pathological parameters. Results: Mean AgNOR counts in gallbladder cancer (11.354 ± 1.7866) were significantly higher than chronic cholecystitis (2.0815 ± 0.3731). Amongst patients with gallbladder carcinoma, well-differentiated (9.5867 ± 1.8928), moderately-differentiated (11.1971 ± 1.3181) and poorly-differentiated adenocarcinoma (13.1829 ± 0.9779) showed statistically significant difference in AgNOR counts. On inter stage comparison, study revealed progressive and statistically significant increase in AgNOR count from Tis to T4 stage. Mean AgNOR count for GBCs without metastasis was lower (10.5186 ± 1.6911) than metastatic GBC (12.2538 ± 1.4581), difference being statistically significant (p=0.009). Discussion and conclusions: Our results demonstrate that AgNOR parameters are useful indicators to evaluate malignant behavior of gallbladder carcinoma and its combination with conventional cytology may increase the diagnostic accuracy. AgNOR index can be used as a rapid, inexpensive and easily performed diagnostic tool to aid in early confirmation of a suspicious case of malignant gallbladder disease.