Multiple primary malignancies are rare and range from 2 to 7%. (1) Choroidal melanoma is the most common intraocular malignancy of adults 40 to 70. The main treatment for choroidal melanoma is enucleation. (2) Developing a second primary after choroidal melanoma is very rare. High-grade Sinonasal undifferentiated carcinomas scarce type of cancer which constitutes less than 3% of sinonasal carcinomas. (3) The main treatment for sinonasal carcinomas is endoscopic removal with or without radiotherapy. Herein, we report a rare case of a 47-year-old female patient diagnosed with undifferentiated sinonasal carcinoma with a previous history of choroidal melanoma of the left eye that patient has undergone exenteration followed by adjuvant radiotherapy. To our knowledge, no association has been reported between sinonasal carcinoma with choroidal melanoma in the literature. 

In the year 2015, 40 years old female came with complaints of pain and redness in her left eye for 1 month which is progressive in nature and pain radiates to left frontal and temporal regions and loss of vision for 1 week. Perception of light was absent in the left eye. Mild lid oedema and inadequate closure of palpebral aperture, conjunctiva congested. Haze cornea due to stromal oedema. The anterior chamber is swallowed. The pupil is fixed and vertically oval. MRI brain and orbit shows ill-defined altered MR signals in the right orbital globe (posterior chamber and vitreous). Enucleation was done in the Department of Ophthalmology, KGMU. Post-operative histopathological examination shows choroidal melanoma. A post-operative CECT scan of the head shows no residual tumour. Post-operative radiotherapy 60gy in 30 fractions at 2gy per fraction given in two phases in cobalt teletherapy machine by Anterior and Right oblique fields with 5 fractions per week over 6 weeks in radiotherapy department, KGMU. Then the patient is followed up in the ophthalmology department every 3 months initially and every 6 months afterwards. The disease-free interval was 7.5 years.

On March 2023, a patient came with complaints of bleeding from the left nasal cavity for 3 months. She was evaluated in the ENT department, at KGMU. Local Examination shows a reddish mass present in the left nasal cavity. Biopsy from the mass shows sinonasal carcinoma. CEMRI paranasal sinuses show 44*58*20 mm soft tissue lesion noted in the left nasal cavity, superiorly extends into the ethmoid sinus, medially abutting the nasal septum, laterally causing erosion of the medial wall of the orbit, and also lesion causing erosion of the medial wall of the left maxillary sinus. Endoscopic removal of nasal mass done April 2023. Post-operative CEMRI Paranasal sinuses show no residual disease. Postoperative HPE shows sinonasal undifferentiated carcinoma with IHC markers CD99 – focal positive, CK7 – negative, EMA – focal positive, Synaptophysin – Negative, CK5/6 – Negative, S 100 – Negative, KI67 – 20%. The patient had disease-free intervals for 3 months. In July 2023, the patient again came with complaints of left nasal blockage and nasal bleeding. Local examination shows a reddish mass present in the left nasal cavity. CECT of the nose and paranasal sinuses shows a 70*46*26 mm space-occupying lesion present on the left nasal cavity extends from anterior nares to posterior choana and the lesion is eroding the medial wall of the left maxillary sinus. Endoscopic removal of the tumour was done. Post-operative HPE shows sinonasal undifferentiated carcinoma with IHC markers Pan-CK – positive, P40 – focal positive and Synaptophysin – negative. Then patient Reirradiated with a dose of 66gy in 33 fractions by IMRT technique in Elekta LINAC machine in radiotherapy department, KGMU. Now the patient is on follow-up without any major complaints.

Figure A: Axial T1-weighted MR image shows that the tumor (*) enhances moderately

Figure B: Dose distribution for a composite plan of a photon intensity-modulated radiotherapy

Multiple primary malignancies in a single patient were first described in 1879 by Billroth. (4) The neoplasms may be limited to a single organ or, as in our case, involve multiple and anatomically separate organs. The North American Association of Central Cancer Registries (NAACCR) classifies multiple primary tumours into two categories: 1. Synchronous, in which the cancers occur at the same time (the Surveillance Epidemiology and End Results Program (SEER) definition is within two months). 2. Metachronous, in which the cancers follow in sequence, that is, more than two months apart. (5) Metachronous primary malignancies are becoming increasingly common because of an increase in the number of elderly cancer survivors, greater awareness, and improved diagnostic modalities. 

Whether the second lesion is truly a primary or represents metastases is difficult to decide and for this, the Warren and Gates criteria (1932) are used which proposed that a diagnosis of multiple primary malignancies requires the following; 1. each tumour should present a definite picture of malignancy, 2. each tumour should be histologically distinct, 3. the possibility that one is a metastasis of the other must be excluded. (4)

There is no sufficient event which supports radiation-induced sinonasal carcinomas. The modified Cahan criteria state that (a) Radiation Malignancies must arise in an irradiated field; (b) a sufficient latency period, preferably more than 4 years, must have elapsed between the initial RT and the alleged induced malignancy; (c) the treated tumour and the alleged induced tumour must have been biopsied, and the two tumours must be different histologically; and (d) the tissue in which the alleged induced tumour arose must have been metabolically and genetically normal before RT exposure. (6)

In our study, patients having metachronous dual primary malignancy are treated with surgery followed by radiotherapy. There is no sufficient evidence to suggest that the second primary (sinonasal carcinoma) was due to radiotherapy which was given to the first primary (choroidal melanoma).

In this study, the patient had metachronous dual primary–choroidal melanoma of the left eye with sinonasal carcinoma of the left nasal cavity and both malignancies were treated by surgical removal and adjuvant radiotherapy. There is no sufficient evidence to suggest that the second primary (sinonasal carcinoma) was due to radiotherapy which was given to the first primary (choroidal melanoma). To our knowledge, no association has been reported between sinonasal carcinoma with choroidal melanoma in the literature. 

1. Coyte A, Morrison DS, McLoone P. Second primary cancer risk - the impact of applying different definitions of multiple primaries: results from a retrospective population-based cancer registry study. BMC Cancer 2014;14:272. 10.1186/1471-2407-14-272 [PMC free article] [PubMed] [CrossRef] [Google Scholar] DOI: 10.1186/1471-2407-14-272

2. Albert DM. Principles and Practice of Ophthalmology. In: Albert, Jakobiec, editors. Philadelphia, PA: W.B. Saunders Co; 1994. pp. 3197–8. Ch. 258. [Google Scholar] https://books.google.co.in/books/about/Principles_and_Practice_of_Ophthalmology.html?id=-21qAAAAMAAJ&redir_esc=y

3. Llorente JL, López F, Suárez C, Hermsen MA. Sinonasal carcinoma: clinical, pathological, genetic and therapeutic advances. Nat Rev Clin Oncol. 2014;11(8): 460–472. [PubMed] [Google Scholar] DOI: 10.1038/nrclinonc.2014.97

4. Warren S, Gates D. Multiple primary malignant tumors: a survey of the literature and a statistical study. American Journal of Cancer. 1932;51:1358–1414. [Google Scholar] https://www.semanticscholar.org/paper/Multiple-primary-malignant-tumors.-A-survey-of-the-Warren/db002e714d10e5dd14b81934601ddfbe2697c060

5. Howe HL, editor. Workshop Proceedings From December 4-6, 2002 in Princeton, New Jersey. Springfield, Ill, USA: North American Association of Central Cancer Registries; 2003. A Review of the Definition for Multiple Primary Cancers in the United States. [Google Scholar] https://link.springer.com/article/10.1023/A:1025667524781

6. Cahan WG, Woodard HQ, Higinbotham NL, Stewart FW, Coley BL. Sarcoma arising in irradiated bone: report of eleven cases. 1948. Cancer 1998;82(1):8–34. Crossref, Google Scholar DOI: 10.1002/(sici)1097-0142(19980101)82:1<8::aid-cncr3>3.0.co;2-w