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CORRESPONDENCE
Year : 2018  |  Volume : 14  |  Issue : 10  |  Page : 815-817

Malignant melanoma metastasizing to tonsil: A rare presentation


1 Department of Radiation Oncology, Regional Cancer Centre, Trivandrum, Kerala, India
2 Department of Pathology, Regional Cancer Centre, Trivandrum, Kerala, India

Date of Web Publication24-Sep-2018

Correspondence Address:
M Biju Azariah
Department of Radiation Oncology, Regional Cancer Centre, Trivandrum - 695 011, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.206863

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 > Abstract 


Malignant melanoma (MM) has a high potential of lymphatic and hematogeneous spread, and metastatic disease is always incurable with a high mortality. We present a rare phenomenon of MM metastasizing to the palatine tonsil.

Keywords: Malignant melanoma, metastasis, tonsil


How to cite this article:
Babu G, Azariah M B, Nair P S, James FV. Malignant melanoma metastasizing to tonsil: A rare presentation. J Can Res Ther 2018;14, Suppl S3:815-7

How to cite this URL:
Babu G, Azariah M B, Nair P S, James FV. Malignant melanoma metastasizing to tonsil: A rare presentation. J Can Res Ther [serial online] 2018 [cited 2020 Oct 27];14:815-7. Available from: https://www.cancerjournal.net/text.asp?2018/14/10/815/206863




 > Introduction Top


Malignant melanoma (MM) is a malignancy of pigment-producing cells (melanocytes). Although cutaneous MM comprises only 3% of all skin cancers diagnosed each year, it accounts for approximately 75% of all skin cancer-related deaths.[1] The overall prognosis of an earlier diagnosed thin tumor is excellent; but once metastasized, it becomes an incurable disease with a high mortality.[2] MM metastasizing to tonsil, though previously reported, is a rare event. Here, we present a similar case which has responded satisfactorily to oral temozolomide.


 > Case Report Top


A 75-year-old gentleman was evaluated for a blackish swelling in the left foot in July 2014 and was diagnosed with MM of the foot. After a negative metastatic workup, he underwent wide excision of the lesion with left inguinal dissection in January 2015 [Figure 1]. Surgical pathology report was suggestive of MM (S-100 positive, HMB 45 diffusely strongly positive) [Figure 2]. Tumor size was 4 cm × 3 cm × 0.9 cm. Margins were negative. The maximum Breslow's thickness was 1 cm. None of the 18 lymph nodes sampled were positive. He was asymptomatic until July 2015 when he presented with odynophagia of 1-month duration. Rigid video laryngoscopy showed bluish-black right tonsillar mass clinically favoring MM metastasis [Figure 3]. The patient had also developed multiple in transit cutaneous metastases in the left lower limb [Figure 4]. His computed tomography of the chest, abdomen, and pelvis was normal except for the heterogeneously enlarged right inguinal node 2.3 cm × 1.8 cm [Figure 5]. Biopsy from the tonsillar lesion was suggestive of MM (S-100 positive, Melan A positive) [Figure 6].
Figure 1: The postoperative primary site with recurrent lesion adjacent to the flap site

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Figure 2: H and E staining of the primary lesion in the foot showing malignant cells with prominent nucleoli and brownish-black pigment in the cytoplasm (×40)

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Figure 3: Blackish metastatic lesion in the right tonsillar fossa

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Figure 4: In transit cutaneous metastasis

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Figure 5: Computed tomography image showing enlarged right inguinal node

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Figure 6: Immunohistochemistry showing positivity for Melan A, S-100, and HMB 45 staining

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Since he had multiple recurrence sites, metastasectomy was not contemplated. The patient did not have access to V600E BRAF mutation testing. Hence, he was started on oral temozolomide 150 mg/m2 for 5 days for every 4 weeks. After 1 month on temozolomide, he showed partial clinical response both in the cutaneous deposits and in the tonsillar lesion [Figure 7]. He was advised to continue on temozolomide.
Figure 7: Minimal clinical response to temozolomide

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 > Discussion Top


MM is an aggressive disease accounting for about 75% of the skin cancer-related deaths. After primary tumor excision, about 30% of the patients developed metastasis in various organs.[3]

In various statistics, the frequency of metastases' diagnosis in certain tissues varies according to the following ranges: Skin ~10%–60%, lung ~10%–40%, extra-regional lymph nodes ~5%–35%, subcutaneous tissue ~5%–35%, central nervous system ~2%–20%, liver ~14%–20%, bone ~4%–17%, adrenal glands ~1%–11%, gastrointestinal tract ~1%–8%, pleura ~5%, pancreas ~3%, heart, kidney, thyroid, and uterus <1%.[4] Metastases to the oral cavity are very rare. Henderson et al. analyzed 8823 patients with cutaneous MM and reported that 54 of them had metastasis to the upper aerodigestive tract, most commonly to the tonsils, tongue, nasopharynx, and lips.[5]

Metastases to the mucosa of the upper aerodigestive tract indicate widespread dissemination of cutaneous melanoma, and the prognosis is poor.[6] There is limited literature on the outcome of metastatic tonsillar melanoma. Median survival after the onset of distant metastases is only 6–9 months, and the 5-year survival rate is <5%.

Patients with oligometastatic disease should be evaluated for the possibility of surgical metastasectomy which might confer survival advantage in selected cases.

Until 2010, dacarbazine (DTIC) was the only Food and Drug Administration-approved chemotherapeutic agent for the treatment of metastatic melanoma, despite response rates of ~10% in phase III trials.

Temozolomide, an oral alkylating agent, has demonstrated efficacy equal to that of DTIC in a randomized phase III trial.[7] The addition of interferon to temozolomide resulted in higher response rates and higher toxicity but with similar survival. The combined use of biologic agents (interleukin-2) and chemotherapeutic drugs can produce response rates of 40%–60% with an approximately 10% complete response rate.[8]

However, the systemic treatment of metastatic MM has changed since 2010. At present, all patients with advanced cutaneous melanoma should have their tumors assayed for the presence or absence of a driver mutation at the V600 site in BRAF. Patients with an acral or mucosal primary tumor that does not contain a BRAFmutation should have their tumor assessed for the presence of a driver mutation in KIT.

For patients without a V600 BRAF mutation, immunotherapy with nivolumab in combination with ipilimumab is recommended.

For patients with a V600 BRAF mutation and a good performance status, immunotherapy (checkpoint inhibition with nivolumab plus ipilimumab) rather than targeted therapy is preferred as the initial systemic therapy. When patient progresses on immunotherapy, targeted therapy against the MAPK pathway with a combination of BRAF plus MEK inhibition (dabrafenib plus trametinib or vemurafenib plus cobimetinib) might be preferred over chemotherapy.[9]

For patients with a V600 BRAF mutation and a poor performance status, MAPK pathway targeted therapy (e.g., dabrafenib plus trametinib) rather than immunotherapy is preferred. Checkpoint inhibitor immunotherapy is an alternative; immunotherapy may be an option for second-line therapy when patients progress after targeted therapy.

For patients without a V600 BRAF mutation but with a KIT mutation, use of a KIT inhibitor (e.g., imatinib) may provide an important treatment option, particularly in patients who have symptomatic disease and/or are not candidates for immunotherapy, preferably in the context of a formal clinical trial.[10]

In our case, since the patient had multiple site recurrence, he could not be taken up for metastasectomy. This patient had no access to V600 BRAF mutation testing. Hence, he was started on temozolomide 150 mg daily for 5 days for every 4 weeks. At the first follow-up, the patient had subjective and objective response both in the in transit metastasis and in the tonsillar deposit. Hence, he was advised to continue on tablet temozolomide.


 > Conclusion Top


MM metastasizing to the tonsillar fossa is a rare but distinct possibility. It usually denotes a widespread metastasis and requires systemic treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Chang DT, Amdur RJ, Morris CG, Mendenhall WM. Adjuvant radiotherapy for cutaneous melanoma: Comparing hypofractionation to conventional fractionation. Int J Radiat Oncol Biol Phys 2006;66:1051-5.  Back to cited text no. 1
    
2.
Lasithiotakis KG, Leiter U, Eigentler T, Breuninger H, Metzler G, Meier F, et al. Improvement of overall survival of patients with cutaneous melanoma in Germany, 1976-2001: Which factors contributed? Cancer 2007;109:1174-82.  Back to cited text no. 2
    
3.
Essner R, Lee JH, Wanek LA, Itakura H, Morton DL. Contemporary surgical treatment of advanced-stage melanoma. Arch Surg 2004;139:961-6.  Back to cited text no. 3
    
4.
Belhocine TZ, Scott AM, Even-Sapir E, Urbain JL, Essner R. Role of nuclear medicine in the management of cutaneous malignant melanoma. J Nucl Med 2006;47:957-67.  Back to cited text no. 4
    
5.
Henderson LT, Robbins KT, Weitzner S. Upper aerodigestive tract metastases in disseminated malignant melanoma. Arch Otolaryngol Head Neck Surg 1986;112:659-63.  Back to cited text no. 5
    
6.
Cauchois R, Laccourreye O, Carnot F, Brasnu D, Monteil JP. Metastatic tonsil melanoma. Ann Otol Rhinol Laryngol 1993;102:731-4.  Back to cited text no. 6
    
7.
Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 2000;18:158-66.  Back to cited text no. 7
    
8.
Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: Time for a change? Cancer 2007;109:455-64.  Back to cited text no. 8
    
9.
Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011;364:2507-16.  Back to cited text no. 9
    
10.
Hodi FS, Friedlander P, Corless CL, Heinrich MC, Mac Rae S, Kruse A, et al. Major response to imatinib mesylate in KIT-mutated melanoma. J Clin Oncol 2008;26:2046-51.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]



 

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