Table of Contents

Original articles

Pattern of Karyotypic aberrations in Pakistani Patients with de novo acute Myeloid leukemia ..........................................................06Syeda Alia Abbas, Sadia Sultan, Sana Ashar, Syed Muhammad Irfan

Tinospora Cordifolia induces Cell Cycle arrest in Human Oral Squamous Cell Carcinoma Cells ...........................................................10Parveen Bansal, Manzoor Ahmad Malik, Satya N Das, Jasbir Kaur

detection Mutations of JaK2 exon 12 in Patients with JaK2 (v617f)-negative Myeloproliferative disorders .....................................15S. Z. Makani, N. Parsamanesh, S. Mirzaahmadi, M. Hashemi, F. Shaveisi-Zadeh, N. Mansouri, M. Ghazi, A. Movafagh

Hepatocellular Carcinoma Peritoneal Metastasis: role of Cytoreductive Surgery and Hyperthermic intraperitoneal Chemotherapy (HiPeC) ......................................................................................................................................................20John Spiliotis, Georgios Nikolaou, Nikolaos Kopanakis, Dimitra Vassiliadou, Alexios Terra, Elias Efstathiou

The effect of dose-volume Parameters on Central nervous System relapse in Pediatric Patients with acute leukemia receiving Prophylactic Cranial irradiation ............................................................................................................24Zeliha Guzeloz, Ayse Nur Demiral, Fatma Eren, Mehmet Adigul, Ahmet Ergin Capar, Handan Cakmakcı, Sebnem Yilmaz, Ozlem Tufekci, Hale Oren, Riza Çetingoz

long-term results of Post-operative Pelvic image guided intensity Modulated radiotherapy in Gynecological Malignancies ........30Rashi Agrawal, Sowmiya Prithiviraj, Dinesh Singh, Vaishali Zamre, Sandeep Agrawal, Arun Kumar Goel, Kanika Gupta, Bala Subramanian

epidemiology and Survival analysis of Gastrointestinal Stromal Tumors in lebanon: real-life Study from a hospital tumor registry, 2000-2015 ....................................................................................................................38Elie El Rassy, Fadi Nasr, Tarek Assi, Toni Ibrahim, Nathalie Rassy, Joseph Bou Jaoude, Marcel Massoud, Georges Chahine

Case reports

Giant Primary Sinonasal Mucosal Melanoma: a rare Malignancy ..........................................................................................................43Mehtab Alam, Mohd Aslam, Piyush Kant Singh, Shahab Farkhund Hashmi, Syed Abrar Hasan

Sarcomatoid Carcinoma of the Maxilla: a Case report with literature review ......................................................................................48Lahcen Khalfi, Yassine Ziani, Mouna Kairouani, Odry Agbessi, Mohammed Kamal Fiqhi, Alae Guerrouani, Karim El Khatib

neuroendocrine Carcinoma of Gall Bladder: a rare Presentation with review of literature .................................................................51Amit Gupta, Parvez Ahmed, Prashant Durgapal, Pooja Kala, Shalinee Rao, Rajesh Pasricha, Sanjeev Misra

Clear Cell variant of Calcifying epithelial Odontogenic Tumor: a rare Clinical entity ............................................................................55Husain Sabir, Subhash Kumbhare, Saurabh Redij, Namrata Gajbhiye

Hodgkin’s lymphoma as a Multiloculated lung Cavity lesion ................................................................................................................61Aisha M. Al-Osail, Hind S. Al-Saif, Mashail M. Al-Hajri, Hajer M. Al-Zuhair, Deemah A. Al-Abdulhadi, Emad M. Al-Osail, Sarah M. Al-Hajri

Breast adenoid Cystic Carcinoma: a rare Case .......................................................................................................................................66Lamiae El Amarti

review articles

industrial Pollutants and nasopharyngeal Cancer: an Open Question ....................................................................................................70Roberto Menicagli, Gianni Bolla, Laura Menicagli, Anastassia Esseiridou

Conference Highlights/Scientific Contributions

• Highlightsofthe1stCombinedGulfCancerConference,CancerAwareness:RealityandAmbition,2-3April2017,Kuwait ........75

• NewsNotes ............................................................................................................................................................................................84

• Advertisements .....................................................................................................................................................................................88

• ScientificeventsintheGCCandtheArabWorldfor2017 ..................................................................................................................89

4343

Case Report

Giant Primary Sinonasal Mucosal Melanoma: a rare Malignancy

Mehtab Alam, Mohd Aslam, Piyush Kant Singh, Shahab Farkhund Hashmi, Syed Abrar Hasan

Department of Otorhinolaryngology, J.N. Medical College, A.M.U, Aligarh, India

abstract

It is extremely rare to find a case of primary sinonasal mucosal melanoma, which is more aggressive and have poorer outcome than its cutaneous counterpart. This tumour is refractory to the treatment which includes wide surgical excision with or without adjuvant post-operative radiotherapy. We are reporting a case of 60 year

old female who presented with right sided nasal mass and facial deformity, in whom the diagnosis of mucosal melanoma was made on histopathological examination and confirmed by immunohistochemistry.

Keywords: Mucosal melanoma, Sinonasal, Immunohistochemistry

Corresponding author: Dr. Mehtab Alam, M.S, Senior Resident, Department of Otorhinolaryngology, J.N.

Medical College, A.M.U, Aligarh, India 202002. Tel. +919411979526

Email: mehtabalam4105@gmail.com

introductionMalignant melanomas in themselves are rare

malignancies and those affecting extra-cutaneous sites are even rarer. Primary malignant melanoma involving sinonasal region accounts for less than 1% of all melanomas and less than 4% of all sinonasal neoplasms (1). They are derived from the neoplastic transformation of melanocytes of neuroectodermal origin, in the basal layer of mucosa. The most common site for mucosal melanomas is in the nasal cavities and sinuses, followed by oral cavity, pharynx, larynx and esophagus (2). Mucosal melanomas tend to occur in an older age group (50 to 80 years) and males are more commonly affected than females (3). Though the melanomas are known for poor outcome, early detection, diagnosis and treatment is beneficial for longer patient survival.

Case descriptionA 60 year-old female patient was brought to the

otorhinolaryngology clinic of J.N. Medical College, with complaints of right sided nasal mass, nasal obstruction, nasal discharge occasionally blood mixed and facial deformity with fullness over right cheek. All these symptoms get aggravated over past 1 month.

Clinical examination of the patient revealed a pinkish-black, firm, slightly tender mass filling whole of the right nasal cavity. The nasolabial angle was lost due to stretching out of the ala (Figure 1). The mass was pushing the nasal septum towards left and extending posteriorly to the choana as evident on posterior rhinoscopy.The overlying skin was normal except for the presence of two moles, which were since her childhood.

The routine biochemical and haematological parameters were within normal limits. Contrast Enhanced Computed Tomography (CECT) of nose and paranasal sinuses was done, which showed an expansile, intensely enhancing soft tissue density lesion centered in right nasal cavity and extending into the right anterior and posterior ethmoid sinuses with expansion of the walls of the right nasal fossa. Anteriorly the mass was extending up to the vestibule and posteriorly up to choana. Erosion of medial orbital wall and nasal bone was also noted, but no

figure 1. Mass filling the right nostril with loss of nasolabial angle

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Sinonasal Mucosal Melanoma, Mehtab Alam, et. al.

intra-orbital or intra-cranial extension was seen on CECT (Figure 2). Based on CECT findings probable diagnosis of malignant nasal mass was made, and under topical local anesthetic spray (10% lignocaine) a small piece of tissue was taken and sent for histopathological examination, which showed a spindle cell neoplasm favoring malignant melanoma (Figure 3).

The diagnosis of malignant melanoma was confirmed by immunohistochemistry, which was positive for S-100 (Figure 4) and Melan-A (Figure 5). A search for distant metastasis was done using ultrasonography and computed tomography, and came out to be negative.

Once the diagnosis of primary sinonasal mucosal melanoma was established, wide surgical excision was done using lateral rhinotomy approach and the mass was

figure 2. Contrast enhanced Computed Tomography showing expansile, intensely enhancing soft tissue density lesion with erosion of medial orbital wall and nasal bone.

figure 3. Histopathological examination revealing pleomorphism and mitosis, favoring a spindle cell neoplasm.

figure 4. immunohistochemical examination showing positive result with S- 100.

figure 5. . immunohistochemical examination showing positive result with Melan- a.

removed with free margins (Figure 6). Grossly the mass consists of multiple, irregular, friable, dark brown pieces of tissue with some bony fragments (Figure 7). Post-operatively the patient underwent radiotherapy and is free from any tumour recurrence after 6 months and only mild scarring of the incision site was noted (Figure 8).

discussionMalignant melanoma arising from mucosal surfaces

of head and neck is very rare and is thought to arise from the melanocyte precursors normally present within the mucosa. American College of Surgeons Commission in 1998 reported that, of all the malignant melanomas only 1.3% were of mucosal origin (4). Nandapalan et al. in a study of 259 cases reported that the most common site for mucosal melanoma was 69% in nasal cavity, 22% in oral cavity and 9% in pharynx, larynx and upper esophagus(2). Isolated malignant melanoma may occur in paranasal sinuses with maxillary sinus being most commonly affected (47%), followed by ethmoids (18%), frontal (14%) and sphenoid sinus (7%) (5).

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The Danish Society for Head and Neck Oncology over a span of 10 years (1982- 1991), reported that out of 315 sinonasal malignancies patients, 34 were diagnosed as having intranasal melanoma (6).

The common presenting symptoms of sinonasal mucosal melanomas are nasal blockade, nasal discharge often blood mixed, but the advanced cases may develop facial deformity, pain, proptosis and diplopia (7). Examination may show a sessile mass, a polyp or even a large obstructing tumour, varying in color, usually pinkish- white to brownish-black (8).

About one-third of sinonasal melanomas are amelanotic. They may be multi-focal, may have satellite lesion, may invade angiolymphatics and can metastasize. Cases have been reported with symptoms due to metastatic melanoma deposits in brain rather than nasal bleed or obstruction (9). In another case symptoms because of gastric metastasis from sphenoid sinus melanoma have been reported (10).For differentiating primary and metastatic melanoma, Billing et al. (11) noted that there is junctional activity in the overlying or adjacent mucosa in primary tumour, while in metastatic disease overlying mucosa is intact.

Though the exact etiopathological basis of mucosal melanoma cannot be made, Zak and Lawson (1974) reported the presence of dendritic melanocytes in the epithelium of sinonasal region (12). Cove reported a case of a malignant primary multifocal intranasal melanoma arising from a pre-existing nasal and maxillary sinus melanosis (13).The sunlight and smoking are believed to be the etiological factors but their role is controversial (14).

The diagnosis of mucosal melanoma can be made on histopathological basis as majority of them produces melanin. The malignant cells are either epithelioid or spindled with enlarged and pleomorphic vesicular nuclei and prominent nucleoli. In amelanotic melanomas diagnostic difficulty may arise as they may mimic other malignancies like lymphoma, sarcoma, and poorly differentiated carcinoma. Invariably in all cases of melanomas, diagnosis can be confirmed by immunohistochemistry and electron microscopy. Identification of melanoma cytoplasmic antigen using HMB 45, and S-100 protein using a polyclonal antibody, appears to identify nearly all cases of melanomas regardless of site (15). Staining for S-100 protein is a sensitive test with immunoreactivity being present in

figure 6. Surgical field after removal of the malignant mass.

figure 7. resected mass consisting of irregular, friable, dark brown pieces of tissue with some bony fragments.

figure 8. Post-radiotherapy clinical picture at 6 months, showing mild scarring at the incision site.

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Sinonasal Mucosal Melanoma, Mehtab Alam, et. al.

86 – 100 percent cases (16). Electron microscope shows presence of melanosomes or pre-melanosomes. Gadolinium enhanced Magnetic Resonance Imaging (MRI) is considered to be the best imaging technique for head and neck mucosal melanomas and Computed Tomography (CT) is often required for bony invasion.

The best treatment modality for primary sinonasal melanoma is radical excision with or without adjuvant post-operative radiotherapy (17), which enhances the chances of control of local disease. De Meerleer et al. (18), emphasized that in inoperable cases post-operative radiotherapy should be administered for good palliation. Chemotherapy is usually reserved as a last resort to terminally ill patients, and Dimethyl triazeno imidazole carboxamide (DTIC) is the most commonly used chemotherapeutic agent for malignant melanoma.

Immunotherapy in the form of BCG vaccine or dextran methyl carboxylic benzyl amide (DMCB) has been tried as treatment modality for melanomas. Recently a three vaccine strategy for melanoma in mice have been tried, comprising of (a) naked DNA, (b) peptide pulsed dendritic cells and, (c) a mixture of peptide and E. coli toxin LTR 72, targeting the tumour antigen. Experiments had shown promising results for peptide pulsed dendritic cell vaccine which can be considered for a trial in human subjects (19).

Malignant melanoma irrespective of site, are known for poor prognostic outcome. Primary site recurrence rate following ablative surgical excision varies from 55% to 82% (20) and overall 5-year survival rate is less than 40% (9).

Consent

Written informed consent for publication of the patient’s clinical details and clinical images was obtained from the patient.

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