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Clear Cell Carcinoma at Soft Palate
Yumuşak Damakta Şeffaf Hücreli Karsinom
Mehmet YAŞAR, MD,1Erhan GÜNERİ, MD,1Hatice KARAMAN, MD,2Aynur AYTEKİN, MD,3 Mustafa SAĞIT, MD,1Cemil MUTLU, MD1
1Kayseri Training and Research Hospital, Clinic of Ear, Nose and Throat, 2Kayseri Training and Research Hospital, Clinic of Pathology, 3Kayseri Training and Research Hospital, Clinic of Radiotherapy, Kayseri
ABSTRACT
Clear cell carcinoma is a rarely encountered low grade tumor arising from salivary gland. It is more commonly seen in women and at palates during fifth or sixth decades of life. Treatment is total surgical excision with negative margins. Here, we aimed to present a novel therapeutic approach with adding ra-diotherapy to surgery in a tumor localized at soft palate and to review literature.
Keywords
Adenocarcinoma, clear cell; salivary gland neoplasms; palate, soft
ÖZET
Clear Cell carcinoma tükrük bezinden köken alan düşük gradeli ender rastlanan bir tümördür. 5-6. Dekatlarda daha çok bayanlarda ve damak yerleşiminde görülür. Tedavisi negatif sınırlarla total cerrahi eksizyondur. Bu olgu sunumundaki amacımız 5. Dekatta yumuşak damak yerleşimli bir tümörün cerrahisi ve radyoterapi eklenerek yapılan farklı bir tedavi yaklaşımını sunmak ve konuyla ilgili mevcut literatürü yeniden gözden geçirmekti.
Anahtar Sözcükler
Adenokarsinom, berrak hücreli; tükürük bezi tümörleri; yumuşak damak
Çalıșmanın Dergiye Ulaștığı Tarih: 02.02.2016 Çalıșmanın Basıma Kabul Edildiği Tarih: 26.04.2016
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Correspondence
Mehmet YAŞAR
Kayseri Training and Research Hospital, Clinic of Ear, Nose and Throat, Kayseri
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INTRODUCTION
umors of salivary gland are rare tumors, ac-counting for 0.5% of all human malignancies. However, these tumors represent 3-5% of all head and neck tumors and are seen more commonly in women during fifth or sixth decades of life.1-3Tumors of
minor salivary glands comprise 10-15% of all salivary gland tumors and most common localization is palate.4-6
More than half of minor salivary gland tumors display malignant characteristics.3Distant metastasis is found
in 9% of malignant minor salivary gland tumors with reports reaching up to 20%.3
Hyalinizing clear cell carcinoma (HCCC) is a rarely seen, indolent tumor arising from minor salivary gland. It comprises less than 1% of all salivary gland tu-mors.7It presents as a submucosal mass lesion without
pain in oral cavity. The most common localization in-cludes palate and tongue.8It may also be seen at oral
mucosa, hypopharynx, nasopharynx, retromolar region, nasal cavity and parotid gland.9
Given the clear cells are glycogen-rich cells, these cells are observed as PAS positive, diastase sensitive and mucicarmin negative. It is also seen that clear cell carcinoma displays positive staining with low- and high-molecular weight keratin, anti-epithelial mem-brane antigen (EMA) and, in some cases, carcinoem-bryonic antigen. Clear cell carcinoma displays negative staining with S-100 protein muscle-specific actin (MSA), smooth muscle actin (SMA), myosin and calponin, indicating lack of myoepithelial differentia-tion.10
It has been reported that wide excision is adequate in the treatment. The positive surgical margins are as-sociated to local and distant metastasis.11In this case
re-port, we presented flap reconstruction of defect in the patient with clear cell carcinoma localized at soft palate. We also emphasized that postoperative radiotherapy was required because the tumor was reported as high-grade clear cell carcinoma. Here, it was aimed to remind treat-ment modalities for clear cell carcinoma by reviewing literature.
CASE REPORT
A 57-years old woman had presented to outpatient clinic one year ago with a growing mass lesion at soft palate over 2 years. Written informed consent was
ob-tained from the patient who participated in this study. She had been offered surgery but she declined to un-dergo surgery. One year after first referral, the patient presented to outpatient clinic with persistent grow of mass lesion and halitosis. An ulcerated, macerated le-sion without bleeding (2.5x1.5 cm in size) was observed at 2 cm lateral to the junction of soft palate and uvula and 1 cm superior to the right tonsillar plica. The mass lesion was observed to be localized beneath intact mu-cosa as ulcerated portion (0.5 cm in size) being excep-tion. The patient had no history of alcohol consumption or smoking. She also had no comorbid disorder. On neck sonography, there was a lymphadenopathy (1x1 cm in size) at right submandibular area, which was in-terpreted as reactive lymph node. Abdominal sonogra-phy was reported as normal. No bone or muscle invasion was observed on maxillofacial MR imaging (Figure 1). An incisional biopsy was performed to the lesion, which was reported as myoepithelial carcinoma, clear cell variant (Figure 2). The patient underwent sur-gery in Rose position under general anesthesia with au-tomatic mouth retractor. Total excision with 5 mm of negative margins was performed. Frozen sections from superior, inferior, medial, lateral and base areas were studied during surgery, which were reported as nega-tive. Thus, the defect was reconstructed by flap inter-polation to surgical site (3x2 cm in size) from buccal region (Figure 3). Flap pedicle was removed one month after surgery. The histopathological examination was re-ported as T2N0 high-grade tumor. Thus, adjuvant ra-diotherapy was indicated. Rara-diotherapy was given at a total dose of 60 Gy in 3 fractions and boost at tumor bed from 7 areas by IMRT technique (LINAC DHX 2300; Varian Co., Palo Alto,CA) using photon energy of 6 MV (Figure 4).
DISCUSSION
HCCC is a novel and rare salivary gland tumor arising from intraoral minor salivary glands.12It is
gen-erally seen at fifth or sixth decades of life and more fre-quent in women than men. Recurrence or metastasis is rare as it is a low-grade neoplasm without pain. Both benign tumors such as oncocytoma or myoepithelioma and malignant tumors such as mucoepidermoid or acinic cell carcinoma can arise from clear cells. Due to
poorer understanding of HCCC, it can be misdiagnosed as poor differentiated carcinoma, squamous cell noma, acinic cell carcinoma, mucoepidermoid
carci-noma and epithelial-myoepithelial carcicarci-noma.13Given
the clear cells are glycogen-rich cells, these cells are observed as PAS positive, diastase sensitive and muci-carmin negative. Thus, definitive diagnosis can be made by specific stains and immunohistochemical tests in HCCC.
As clear cells in the mucoepidermoid carcinoma have mucin in the cytoplasm, positive staining with mu-cicarmin can be helpful in differential diagnosis. In on-cocytoma, glycogen-rich clear cells have abundant mitochondria and these cells are stained positive with phosphotungstic acid hematoxylin. In acinic cell carci-noma, tumor cells are PAS positive and diastase resist-ant and also have zymogene. Neoplastic cells are stained positive with S-100 protein and SMA in epithelial/my-oepithelial carcinoma and malignant myoepithelioma but not in HCCC.13
Specific stains have limited contribution to dis-crimination between clear cell carcinoma and odonto-genic tumors; however, odontoodonto-genic tumors can be discriminated from clear cell carcinoma by biphasic growth pattern and positive staining for cytokeratin and S-100 protein.9
Metastatic tumors of oral cavity originate from renal cell carcinoma and thyroid carcinomas and less commonly from intestinal tumors, hepatic carcinoma and prostate carcinoma. Neoplastic cells in renal cell carcinoma are stained positive with cytokeratin and mentin while HCCC displays negative staining with vi-mentin.
Clear cell carcinoma is a rare tumor; thus, limited number of treatment protocol exists. Since it is a tumor with low malignant potential, treatment protocol in-cludes surgical excision regardless of pre- or post-oper-ative radiotherapy. Recurrence rate is approximately
15-18%.1Regional lymph node metastasis was reported
in a few cases while pulmonary metastasis was reported in 2 cases.14Although number of mitosis is increased in
such cases, supportive findings for metastasis can be lacking.
Jin et al. described EWSR1 gene in a patient with recurrent clear cell at tongue.14It has been proposed
that high-grade HCCC transformed from low grade tumor after radiotherapy lead to recurrent cases. In this case, it was seen that neoplastic process persisting at
Clear Cell Carcinoma at Soft Palate 15
Turkiye Klinikleri J Int Med Sci 2008, 4 15
Figure 2. Positive staining of tumor cells for pankeratin (IHC, x200).
Figure 3. Intraoperative intraoral view of tumor.
KBB ve BBC Dergisi 24 (1):13-6, 2016
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all surgical margins manifested with loco-regional re-currences after 6 years. It was proposed that this was due to high grade HCCC. As local recurrence rate is low, clinical-pathological examination and long-term follow-up are essential to document biological behav-ior of this carcinoma. Hakeem et al. reported that only 2 of 20 cases with myoepithelioma was clear cell vari-ant localized at palate and suggested that the lesion is extremely rare.15
CONCLUSION
It isn’t difficult to identify clear cell morphology in histopathological sections but it is warranted to es-tablish cytoplasmic content and its source by specific stains. Biological behavior is unclear in this rare tumor and clinical-pathological examination and long-term follow-up are needed.
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