|Year : 2016 | Volume
| Issue : 2 | Page : 44-47
Extremely rare and fulminant case of small cell carcinoma of submandibular salivary gland
Abhishek Purkayastha, Neelam Sharma, Virender Suhag, Tejas Pandya
Department of Radiation Oncology, Army Research and Referral Hospital, New Delhi, India
|Date of Submission||19-May-2016|
|Date of Acceptance||07-Jun-2016|
|Date of Web Publication||1-Jul-2016|
Department of Radiation Oncology, Army Research and Referral Hospital, Dhaulakuan, Delhi Cantonment, New Delhi 110010
Source of Support: None, Conflict of Interest: None
Small cell carcinomas (SmCCs) usually have a pulmonary origin. Extrapulmonary sites such as salivary glands of head and neck are extremely rare, posing a diagnostic and therapeutic dilemma for treating oncologists due to its location, vast array of differential diagnosis, and very few reported cases without any definite therapeutic guidelines. We report an exceedingly uncommon case of SmCC of submandibular salivary gland in a 29-year-old male presenting with right-sided neck swelling, underwent surgery and adjuvant radiotherapy (RT). However, within 3 weeks, he presented with frontal, ethmoidal, and intracranial tumor extension and bone and lung metastasis, for which he received palliative RT and chemotherapy. However, he was unable to tolerate the treatment and finally succumbed to this fulminant illness. A thorough review of literature reveals that our case is to be listed as the tenth and also the most fulminant case of this pathology that have ever been reported in world literature till date.
Keywords: Immunohistochemistry, radiotherapy, small cell carcinoma, submandibular salivary gland
|How to cite this article:|
Purkayastha A, Sharma N, Suhag V, Pandya T. Extremely rare and fulminant case of small cell carcinoma of submandibular salivary gland. Transl Surg 2016;1:44-7
|How to cite this URL:|
Purkayastha A, Sharma N, Suhag V, Pandya T. Extremely rare and fulminant case of small cell carcinoma of submandibular salivary gland. Transl Surg [serial online] 2016 [cited 2019 Jun 24];1:44-7. Available from: http://www.translsurg.com/text.asp?2016/1/2/44/185199
| Introduction|| |
Small cell carcinoma (SmCC) of the salivary glands accounts for < 1% of all salivary gland tumors  found predominantly in the parotids while submandibular gland origin is rarely heard of. SmCCs are highly aggressive tumors with a dismal prognosis and need to be managed with multimodality treatment on a case-to-case basis. The aim of this report is to highlight an extremely rare and aggressive case of SmCC of submandibular salivary gland as it posed a diagnostic and therapeutic challenge due to its rarity, vast array of differential diagnosis, highly fulminant behavior, and scarcity of relevant literature.
| Case Report|| |
A 29-year-old male with no known comorbidities, smoking history, addiction, any occupational exposure, or any significant family history presented with swelling over the right side neck of 4 months duration. Clinically, a 5 cm × 4 cm swelling was palpable of cervical levels Ib and II on the right side neck. His routine hematological and biochemical profiles were normal. Ultrasonography of the neck showed an enlarged right submandibular gland with multiple well-defined ipsilateral lymph node levels II, III, and IV. Fine-needle aspiration cytology (FNAC) of the right submandibular gland showed small round cell tumor. Computed tomography scan of the face and neck showed a large 7.2 cm × 5.8 cm × 8.5 cm mass lesion on the right submandibular region as shown in [Figure 1] and lymph nodes at right levels, i.e., II, III, and IV. Metastatic work-up with bone scan and positron emission tomography (PET) scan were suggestive of localized disease.
|Figure 1: Computed tomography scan of the face and neck showing mass lesion on the right submandibular region|
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The patient underwent right submandibular gland excision where a 10 cm × 8 cm mass was excised with right modified radical neck dissection. However, on the 4 th postoperative day, the patient developed a swelling over the surgical site, which gradually progressed to a size of approximately 7 cm × 5 cm and another erythematous swelling over nose as shown in [Figure 2]. Postoperative histopathological report (HPR) showed solid sheets of round-to-oval tumor cells showing alveolar pattern at places exhibiting scanty cytoplasm, condensed chromatin with absence of nucleoli as shown in [Figure 3]. Foci showing crush artifacts along with active and atypical mitosis with large areas of tumor necrosis were noted. Immunohistochemistry (IHC) was positive for synaptophysin [Figure 4], chromogranin [Figure 5], neuron-specific enolase (NSE), cytokeratin [Figure 6], epithelial membrane antigen (EMA), Leu 7, and CD 56 while negative for thyroid transcription factor-1 (TTF-1), vimentin, CD-99, leukocyte common antigen (LCA), desmin, S-100, melan A, cytokeratin 20, and terminal deoxynucleotidyl transferase (TdT), suggestive of SmCC of submandibular salivary gland. FNAC from the nose lesion was also suggestive of small round cell tumor.
|Figure 2: Patient with postoperative swelling on the right side of neck and nose|
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|Figure 3: Postoperative histopathological report showing solid sheets of round-to-oval tumor cells showing alveolar pattern at places exhibiting scanty cytoplasm, condensed chromatin with absent nucleoli (H and E, × 40)|
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The patient was treated with adjuvant radiotherapy (RT) by three-dimensional conformal RT to the right side face and neck with photons and to nose lesion with electrons to a dose of 66 Gy in 33 fractions. He showed a significant response to therapy with resolution of the right neck swelling. However, within 3 weeks, he presented with severe headache, vomiting, nasal stuffiness, proptosis, peri-orbital and facial swelling. Magnetic resonance imaging brain showed mass lesions in bilateral ethmoid sinuses and bilateral basi-frontal lobes [Figure 7] with resorption of bilateral medial orbital walls and soft tissue extension into retro-orbital region causing proptosis. He was treated with palliative RT to brain, bilateral frontal, and ethmoid sinuses at a dose of 30 Gy in 10 fractions, but developed painful bony metastasis to the right clavicle [Figure 8], for which he was treated with palliative RT to a dose of 20 Gy in 5 fractions. However, he subsequently developed extensive pulmonary metastasis, for which he was exhibited palliative chemotherapy with injection cisplatin and etoposide, but finally succumbed to his metastatic illness.
|Figure 7: Magnetic resonance imaging brain showing mass lesions in bilateral ethmoid sinuses and bilateral basi-frontal lobes (yellow pointer)|
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|Figure 8: Patient showing bone metastasis to the right clavicle (yellow pointer)|
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| Discussion|| |
SmCC of the salivary glands is an extremely rare and unusual tumor accounting for < 1% of all major salivary gland  and 2.8% of all minor salivary gland tumors.  SmCC is primarily a pulmonary neoplasm, while only 4% arise in extrapulmonary sites such as pancreas, prostate, esophagus, uterus, breast, thymus, gastrointestinal tract, skin, kidney, and salivary glands of the head and neck  including larynx, pharynx, paranasal sinuses, and oral cavity.  In world literature, SmCC of major and minor salivary glands has been scarcely reported. A case series of anaplastic SmCC of minor salivary glands was reported by Koss et al. in 1972. Recant and Lacy  reported an undifferentiated SmCC of the parotids with Cushing's syndrome in 1963. Two cases of SmCC of parotid with squamous differentiation were reported by Leipzig and Gonzales-Vitale  in 1982 while Kraemer et al.  in 1986 reported three cases of SmCC of the parotid gland. Gnepp et al. in 1986 reported six cases of the submandibular gland SmCC. The oldest patient was 84-year-old and youngest was 33-year-old with an average age distribution of 61-year-old. Three patients were males and the other three were females. Maximum clinical tumor size was of 2 cm, the average duration of appearance of symptoms and signs was more than 12 months with the mean overall survival of 57 months after treatment. Toyosawa et al. in 1999, de Vicente Rodrĕguez et al.  in 2004, and Scaduto et al. in 2012 have reported solitary cases of undifferentiated SmCC of submandibular salivary glands in older patients. Our case may be the tenth ever reported in a 29-year-old male with a 5 cm × 4 cm neck swelling of 4 months duration who survived for just over 3 months after therapy.
SmCC and large cell carcinoma are the 2 forms of neuroendocrine tumor of the major salivary glands, which are further classified as well differentiated, moderately differentiated, and undifferentiated carcinomas, which account for only 0.3-3% of all salivary gland neoplasms.  Neuroendocrine carcinoma (NEC) is very rare in head and neck region and even rarer in salivary glands with a poor prognosis in view of recurrence, loco-regional, and distant metastasis.  However, many studies ,,,,, have suggested a ductal origin of most of the SmCCs of salivary gland instead of true NEC in view of duct-like arrangement of tumor cells and absence of neurosecretory granules typical of NECs. Salivary duct carcinomas are rare, high-grade, malignant, and aggressive tumors representing 1-3% of all salivary gland malignancies and predominantly affecting males in their seventh decade of life; however, our patient presented at a much younger age. It has a high rate of cervical metastasis with > 50% of the patients having lymph node metastasis at the time of diagnosis.  Gnepp et al. reported identical biologic behavior of both neuroendocrine and ductal types of SmCC of salivary glands with a better prognosis than small cell lung carcinoma. Regarding potential carcinogenesis of SmCC of submandibular salivary glands unlike its pulmonary counterpart, no risk factors such as cigarette smoking, addiction to certain drugs, exposure to environmental pollutants, workplace exposure to asbestos, radon, arsenic, any family history, or prior exposure to radiation has been identified  as was also evident in our case.
Histologically, these tumor cells are described as high-grade neoplasms comprising sheets, ribbons, or nests of round-to-oval cells larger than a normal small lymphocyte , with ill-defined boundaries, scanty cytoplasm, pyknotic nuclei, and abundant mitotic figures. , Crush artifacts and perineural invasion are frequently observed which were seen in the HPR of our patient. IHC plays an important role in differentiating between a primary salivary gland SmCC and other pathologies with small round cell tumor appearing at similar head and neck site such as basaloid squamous cell carcinoma, salivary gland tumors with high-grade transformation, poorly differentiated synovial sarcoma, Ewing's sarcoma, lymphoma, melanoma, olfactory neuroblastomas, rhabdomyosarcomas, or even metastasis from other primary carcinomas such as lung or retinoblastoma. On IHC analysis, the tumor cells react positively with synaptophysin, chromogranin, NSE,  EMA, Leu 7,  and CD 56, apart from cytokeratin staining. A battery of IHC markers such as TTF-1, vimentin, CD-99, LCA, desmin, S-100, melan A, and terminal TdT were negative, thus ruling out other pathologies and metastasis, thus confirming the diagnosis of SmCC of submandibular salivary gland.
Current treatment recommendations are total or radical salivary gland excision with neck dissection. The efficacy of postoperative radiation therapy is unclear; however, in view of the poor prognosis of this tumor, most patients are treated with adjuvant RT  as was practiced by Gnepp et al.  and also by us. At present, no established evidence exists in literature regarding the exact role of chemotherapy in the management of SmCC of submandibular salivary gland except for Scaduto et al. who used chemotherapy as an adjuvant modality. Our report may be the very first case of SmCC of submandibular gland recurring within 4 days of surgery and within 3 weeks of adjuvant RT developing local and intracranial extension followed by distant metastasis to bone and lung. We, therefore, infer that primary SmCC of submandibular salivary gland is a highly malignant and aggressive neoplasm with a tendency for early loco-regional recurrence and distant metastasis with a fulminant course. A thorough history and physical examination followed by loco-regional imaging and functional imaging with PET scan is also essential to rule out any metastasis to the salivary gland from SmCC of other primary sites in the body. An IHC is of utmost importance to predict the exact pathology as emphasized above to determine the optimal treatment algorithm for this neoplasm. Henceforth, we recommend that the diagnosis of SmCC of submandibular salivary gland should always be taken into consideration whenever any patient of any age group presents with a neck swelling so as to enable a prompt initiation of appropriate treatment, and more such cases should be reported to formulate a definitive treatment guideline in future.
We thank the patient and his NOK for allowing us to publish the case report after his death and use the images taken during his stay in hospital. Ethical approval: Written informed consent to publication was obtained from the patient while he was alive. We also like to extend our gratitude to the departments of Pathology and Molecular Science, Surgical Oncology, Medical Oncology, Nuclear Medicine, and Radiology, Army Research and Referral Hospital, New Delhi, India. The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and each author believes that the manuscript represents honest work.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Nagao T, Gaffey TA, Olsen KD, Serizawa H, Lewis JE. Small cell carcinoma of the major salivary glands: Clinicopathologic study with emphasis on cytokeratin 20 immunoreactivity and clinical outcome. Am J Surg Pathol
Koss LG, Spiro RH, Hajdu S. Small cell (oat cell) carcinoma of minor salivary gland origin. Cancer
Levenson RM Jr., Ihde DC, Matthews MJ, Cohen MH, Gazdar AF, Bunn PA Jr., Minna JD. Small cell carcinoma presenting as an extrapulmonary neoplasm: Sites of origin and response to chemotherapy. J Natl Cancer Inst
Recant L, Lacy P. Clinicopathological conference: Cushing′s syndrome associated with a parotid gland tumor. Am J Med
Leipzig B, Gonzales-Vitale JC. Small cell epidermoid carcinoma of salivary glands. ′Pseudo′-oat cell carcinoma. Arch Otolaryngol
Kraemer BB, Mackay B, Batsakis JG. Small cell carcinomas of the parotid gland. A clinicopathologic study of three cases. Cancer
Gnepp DR, Corio RL, Brannon RB. Small cell carcinoma of the major salivary glands. Cancer
Toyosawa S, Ohnishi A, Ito R, Ogawa Y, Kishino M, Yasui Y, Kitamura R, Matsuya T, Ishida T, Ijuhin N. Small cell undifferentiated carcinoma of the submandibular gland: Immunohistochemical evidence of myoepithelial, basal and luminal cell features. Pathol Int
de Vicente Rodríguez JC, Fresno Forcelledo MF, Junquera Gutiérrez LM, Hernández Vallejo G, López Arranz JS. Small cell undifferentiated carcinoma of the submandibular gland with neuroendocrine features. Ann Otol Rhinol Laryngol
Scaduto M, Matrka L, Shah M, Wakely P
Jr., Ozer E. Poorly differentiated small-cell neuroendocrine carcinoma of the submandibular gland: A case report. Ear Nose Throat J
Eneroth CM. Histological and clinical aspects of parotid tumors. Acta Otolaryngol
Jaehne M, Roeser K, Jaekel T, Schepers JD, Albert N, Löning T. Clinical and immunohistologic typing of salivary duct carcinoma: A report of 50 cases. Cancer 2005;103(12):2526-33.
Mair S, Phillips JI, Cohen R. Small cell undifferentiated carcinoma of the parotid gland. Cytologic, histologic, immunohistochemical and ultrastructural features of a neuroendocrine variant. Acta Cytol
Baca JM, Chiara JA, Strenge KS, Keylock JB, Jones CL, Harsha WJ. Small-cell carcinoma of the parotid gland. J Clin Oncol
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