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1 CUTANEOUS METASTASES IN SQUAMOUS CELL CARCINOMA OF THE LARYNX - CASE REPORT METASTAZE CUTANATE CU PUNCT DE PLECARE DE LA UN CARCINOM SCUAMOS LARINGIAN PREZENTARE DE CAZ Loredana Elena Stoica 1), Rucsandra Cristina Dascălu 1), Claudia Cîrstea 1), Raluca Niculina Ciurea 2), Otilia Constantina Rogoveanu 3), Andreea-Oana Enache 1) 1) Dermatology Department, University of Medicine and Pharmacy of Craiova, Romania 2) Pathology Department, University of Medicine And Pharmacy of Craiova, Romania 3) Department of Physical Medicine and Rehabilitation, University of Medicine and Pharmacy of Craiova, Romania Cite this article: Loredana Elena Stoica, Rucsandra Cristina Dascălu, Claudia Cîrstea, Raluca Niculina Ciurea, Otilia Constantina Rogoveanu, Andreea- Oana Enache. Cutaneous metastases in squamous cell carcinoma of the larynx Case report. RoJCED 2015; 2(4): Keywords: cutaneous metastasis, squamous cell carcinoma, larynx, histopathology Abstract Corresponding author: Loredana Elena Stoica, MD, PhD, University of Medicine and Pharmacy from Craiova, Petru Rareș Street, No2-4, , Craiova, Romania, phone: , tanaseloredanaelena@yahoo.com addresses of the others authors: Andreea-Oana Enache oana.popescu86@yahoo.com Raluca Ciurea - raluca1ciurea@gmail.com Rucsandra Cristina Dascălu rucsandrag@yahoo.com Claudia Cîrstea claudia_cirstea22@yahoo.com Otilia Constantina Rogoveanu otilia.rogoveanu@gmail.com Acknowledgement This paper was published under the frame of European Social Fund, Human Resources Development Operational Programme , Project No. /159/1.5/S/ Open Access Article Cutaneous metastasis from head and neck cancers are rare but, when are present, they are usually considered a poor prognostic sign. We report a patient who showed multiple skin metastases 28 months after the diagnosis and treatment of a laryngeal carcinoma. A 57-year-old male with past history of smoking, was referred to our department in 2015 for the presence of 21 skin tumors, varying in size between 0.5 and 2 cm, red-pink in color, depressed center, located on the scalp, face, trunk and limbs. In 2012, the patient underwent total laryngectomy followed by chemoradiotherapy for a squamous cell carcinoma of the subglottic larynx stage IV (T4N2MX). The histopathological exam (double biopsy one from the scalp and the other from the right thigh) shows proliferation of malignant tumor cells arranged in islands in deep dermis, cells with marked atypia, multiple atypical mitoses and unicellular keratinization. Based on clinical and paraclinical examinations we established the diagnosis of cutaneous metastases with laryngeal neoplasm starting point, excluding other conditions that might be confused from clinical point of view. After confirmation of the cutaneous metastasis, the patient was directed the Oncology Department for adequate treatment. The clinical polymorphism of cutaneous metastasis raises numerous problems of clinical diagnosis, leading to significant delays in diagnosis and initiation of treatment. 260

2 Loredana Elena Stoica, Rucsandra Cristina Dascălu, Claudia Cîrstea, Raluca Niculina Ciurea, Otilia Constantina Rogoveanu, Andreea-Oana Enache Rezumat Cuvinte-cheie: metastaze cutanate, carcinom spinocelular, laringe, histopatologie Metastazele cutanate cu punct de plecare de la un cancer cu localizare la nivelul extremității cefalice sunt rare, dar atunci când apar, reprezintă un factor de prognostic nefavorabil. Prezentăm un bolnav cu multiple metastaze cutanate apărute la 28 de luni de la diagnosticul și tratamentul unui carcinom laringian. Pacient în vârstă de 57 ani, fost fumător, se prezintă în clinica noastră în 2015 pentru 21 de formațiuni tumorale, cu dimensiuni cuprinse între 0,5 și 2 cm, culoare roz-roșietică, cu centrul deprimat, localizate la nivelul scalpului, faciesului, trunchiului și membrelor. În 2012 pacientul a suferit laringectomie totală urmată de chimioradioterapie pentru un carcinom spinocelular laringian subglotic stadiul IV (T4N2MX). Examenul histopatologic (dublă biopsie de la nivelul scalpului și coapsei drepte) a relevat proliferare de celule tumorale maligne, dispuse în insule situate în dermul profund, celule cu atipii marcate și prezența de mitoze atipice și keratinizare unicelulară. Pe baza aspectelor clinice și paraclinice am precizat diagnosticul de metastaze cutanate cu punct de plecare de la un carcinom laringian, excluzând multiple afecțiuni confundabile din punct de vedere clinic. După confirmarea metastazelor cutanate, bolnavul a fost îndrumat către Departamentul de Oncologie pentru stabilirea schemei optime de tratament. Polimorfismul clinic al metastazelor cutanate ridică numeroase probleme de diagnostic diferențial determinând astfel întârzierea diagnosticului și inițierea terapiei. Introduction Cutaneous metastases are encountered in 0.7-9% of all skin tumors [1]. Cutaneous metastasis from head and neck cancers are rare but, when present, they are usually considered a poor prognostic sign. The incidence of cutaneous metastasis from head and neck squamous cell carcinoma (SCC) is less than 1% [2]. Clinical case A 57-year-old male, with past history of smoking, presented in 2015 in our department with 21 skin tumors, varying in size between 0.5 and 2 cm, red-pink in color, depressed center, some of them covered by purulent deposits and hematic crusts, other with keratotic surface. The tumors were located on the scalp (13), face (1), trunk (2) and limbs (5) (Figure 1-3). The patient affirms that the tumors appeared about six months ago, initially on the left hand (index), with rapid extension at the regions previously described. In 2012 our patient underwent total laryngectomy extended to the first tracheal ring with jugular and carotid lymph node dissection followed by chemoradiotherapy for a squamous cell carcinoma of the subglottic larynx stage IV (T4N2MX). The pathological examination confirmed the diagnosis of moderately differentiated squamous carcinoma. There were no other known environmental and family risk factors. At clinical examination the patient was afebrile and appeared pale and debilitated with marked asthenia. He had a palpable, mobile and painful left retromandibular lymphadenopathy and right supraclavicular lymphadenopathy. We also retained the presence of a tracheostomy tube. The patient is Fitzpatrick skin type III. The patient had undergone severe weight loss. Dermoscopic examination of skin tumors revealed the pink homogeneous structureless areas, serpentine and linear irregular vessels asymmetrically distributed, polymorphic vessels (dotted vessels, comma-like vessels, hairpin vessels) (Figure 4). The histopathological exam (double biopsy one from the scalp and the other from the right thigh) shows proliferation of malignant tumor cells arranged in islands in deep dermis, cells with marked atypia, multiple atypical mitoses and unicellular keratinization (Figure 5,6). This aspects confirm the metastases of squamous cell carcinoma. Routine hematological investigations did not reveal any pathology other than severe anemia (Hb November

3 1 2 Figure 1-3. Multiple skin tumors varying in size between 0.5 and 2 cm, red-pink in color, depressed center, some of them covered by purulent deposits and hematic crusts, other with keratotic surface, located on the face, scalp, trunk 7.5 mg/dl). Biochemical parameters and routine urine examination were normal. HIV and VDRL tests were negative. Ultrasonography of superficial lymph nodes: retromandibular lymphadenopathy 13/5 mm in diameter and right supraclavicular lymphadenopathy of 10/5 mm diameter. CT scan found tissue nodules on both lung fields, multiple supratentorial brain metastases with maximum axial diameter of 14 mm and perilesional edema. Based on clinical and paraclinical examinations we established the diagnosis of cutaneous metastases with laryngeal neoplasm starting point, secondary severe anemia and also brain and lung metastases. After confirmation of the cutaneous metastasis, the patient was directed to Oncology Department for adequate treatment. Discussions SCC is the most common tumor in upper respiratory tract being also the primary cause of carcinoma of the larynx in adults [3]. Distant metastases in SCC of the larynx occur with an incidence of % and the most frequently involved organs are the lungs, the liver and the bones [1,4]. Cutaneous metastases, when they occur, are usually located on the neck, chest, scalp, face, arms and fingers [5]. The mechanism of skin metastasis in squamous cell carcinoma of subglottic larynx is not fully understood. There are three possible mechanisms: direct spreading, lymphatic and hematologic spreading. Direct spreading is made by direct invasion of the surrounding tissues. Spread through dermal lymphatics can result in the development 3 of cutaneous metastases. The hematogenous spread is made by pulmonary circulation or by azygos and vertebral venous plexus [6]. The clinical picture of cutaneous metastasis varies from macules, infiltrated or indurated plaques, discoid lesions, nodular tumors with telangiectasias, bullous or papulosquamous lesions, to scarred plaques or pigmented tumors [7]. Cutaneous metastases are mostly multiple and rarely solitary, as was seen in our case [8]. In all cases, a high index of clinical suspicion is mandatory for diagnosis of skin metastases. As a rule, biopsy is mandatory in patients with a history of cancer, especially if there are associated symptoms like weight loss, fatigue or severe anemia [9]. Based on clinical exam and paraclinical explorations we excluded the following diagnosis: skin cancers (basal cell carcinoma, sarcoma, etc.), eruptive keratoacanthoma, cutaneous pseudolymphoma, cutaneous manifestation of leukemia. Cutaneous metastases are early indicators for invasive metastatic cancers and usually are associated with limited survival period [10]. Rarely they can 262

4 Loredana Elena Stoica, Rucsandra Cristina Dascălu, Claudia Cîrstea, Raluca Niculina Ciurea, Otilia Constantina Rogoveanu, Andreea-Oana Enache Figure 4. Dermoscopic aspect - pink homogeneous structureless areas, serpentine and linear irregular vessels asymmetrically distributed, polymorphic vessels (dotted vessels, comma-like vessels, hairpin vessels) Figure 5. Proliferation of malignant tumor cells arranged in islands in deep dermis, HE stain X 40 be the first sign of an unknown malignancy [11]. In our case, the primitive tumor was already known. In % of cases, the laryngeal cancer diagnosis is established in advanced stages (stage III, IV), situation encountered also in our case. In stage III and IV of subglottic larynx cancer the 5-year relative survival, is % [12]. In our case, the prognosis is poor, given the large number of cutaneous metastasis and due to the presence of visceral metastases. In patients with laryngeal cancer the risk of developing the second tumor is estimated at 10-24% of cases [13]. There is no agreed consensus in the management and treatment of cutaneous metastasis with laryngeal neoplasm starting point. Treatment and prognosis depend mainly on the type and stage of the primary tumor, cutaneous metastases usually being associated with poor prognosis. In case of multiple cutaneous metastases the aim of the treatment is to provide symptomatic relief and to improve the quality of life. In the case of disseminated disease with multiple skin metastases, the treatment is mainly palliative including surgery, hypofractionated radiation therapy, chemotherapy, and their combinations [14,15]. The median overall survival is significantly improved (by 2,7 months) after the administration of cetuximab with platinum/5fu versus chemotherapy alone. [16,17]. Photodynamic therapy and carbon dioxide laser therapy also can be useful for palliation of skin metastases [18,19]. An early diagnosis and a good follow-up can help greatly in reducing morbidity and mortality. Figure 6. Cells with marked atypia, multiple atypical mitoses and unicellular keratinization. HE stain X 200 Conclusions The clinical polymorphism of cutaneous metastasis raises numerous problems of clinical diagnosis, leading to significant delays in diagnosis and initiation of treatment. Although the disease depends on the underlying malignancy and its therapeutic response, cutaneous metastases are usually associated with poor prognosis. The authors have declared no conflict of interest. This work is licensed under a Creative Commons Attribution 4.0 Unported License. The images or other third party material in this article are included in the article s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit November

5 Bibliography 1. Jain A, Chauhan M, Pandit A, Kumar R, Sharma A, Dubey I. FDG PET/CT in a rare case of multiple cutaneous metastases in carcinoma larynx. Indian Journal of Nuclear Medicine : IJNM : The Official Journal of the Society of Nuclear Medicine, India. 2012;27(4): Rahman, Tashnin et al. Cutaneous Metastasis from Squamous Carcinoma of the Base of Tongue. North American Journal of Medical Sciences 7.1 (2015): PMC. Web. 17 Oct Adams GL, Maisel RH. Malignant tumors of the larynx and hypopharynx. In: Cummings CW, Fredrickson J, Harker LA, editors. Otolaryngology head and neck surgery. 3rd ed. St. Louis: Three Mosby Company; p Krunic AL, Cockerell CJ, Truelson J, Taylor RS. Laryngeal squamous cell carcinoma with infradiaphragmatic presentation of skin metastases. Clin Exp Dermatol Mar;31(2): Kumar N, Bera A, Kumar R, Ghoshal S, Angurana SL, Srinivasan R. Squamous Cell Carcinoma Of Supraglottic Larynx With Metastasis To All Five Distal Phalanges Of Left Hand. Indian Journal of Dermatology. 2011;56(5): Bottoni U, Inocenzi D, Mannooranparampic TJ, Richetta A, Del Guidice M, Calvieri S. Inflammatory cutaneous metastases from laryngeal carcinoma. Eur J Dermatol. 2001;11: Nashan D, Müller ML, Braun-Falco M, Reichenberger S, Szeimies RM, Bruckner-Tuderman L. Cutaneous metastases of visceral tumours: a review. J Cancer Res Clin Oncol Jan; 135(1): Dey A, Sinha RT. Cutaneous metastasis as an initial presentation of an unknown primary. Clin Cancer Investig J 2015;4: Wong CYB, Helm MA, Kalb RE, Helm TN, Zeitouni NC. The Presentation, Pathology, and Current Management Strategies of Cutaneous Metastasis. North American Journal of Medical Sciences. 2013;5(9): doi: / Karki S, Pathak R, Manandhar U, Koirala S. Metastatic cutaneous and subcutaneous lesions: Analysis of cases diagnosed on fine needle aspiration cytology. J Pathol Nepal 2011;1: Dey A, Sinha RT. Cutaneous metastasis as an initial presentation of an unknown primary. Clin Cancer Investig J. 2015;4: American Joint Committee on Cancer. Larynx. In: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010: A.D Heroiu, C. E Danciu, C. R Popescu. Multiple cancers of the head and neck. Mædica 8.1 (2013): H Kavgaci, B Yildiz, U Cobanoglu, E Fidan, F Ozdemir, Fazil Aydin. Laryngeal Squamous Cell Carcinoma with Knee and Heel Skin Metastases: A Case Report. Acta Dermatovenerol Croat 2010;18(1): Kumar N, Kumar R, Bera A., Kumar P, Angurana S. L., Ghosal, S. (. Palliative and Supportive Care in Acrometastasis to the Hand: Case Series. Indian Journal of Palliative Care, 2011:7(3), Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359: Mesía R, Rivera F, Kawecki A, et al. Quality of life of patients receiving platinum-based chemotherapy plus cetuximab first line for recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol 2010;21: L. K. Simpson, L. S. Ostlere, C. Harland. S. Gharaie. Treatment with carbon dioxide laser of painful skin metastases from a laryngeal neuroendocrine carcinoma. Clin Exp Dermatol Dec;34(8):e Karrer S, Szeimies RM, Hohenleutner U, Landthaler M. Role of lasers and photodynamic therapy in the treatment of cutaneous malignancy. Am J Clin Dermatol. 2001;2(4):