Oncocytic mucoepidermoid carcinoma with lymph node metastasis: A report of a rare case with review of literature

Oncocytic mucoepidermoid carcinoma with lymph node metastasis: A report of a rare case with review of literature

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ARTICLE IN PRESS Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (2016) xxx–xxx

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Case Report

Oncocytic mucoepidermoid carcinoma with lymph node metastasis: A report of a rare case with review of literature Wonchibeni T. Murry, Sonal Sharma ∗ , Bharat Singh, Priyanka Gogoi Department of Pathology, University College of Medical Sciences & GTB Hospital, Delhi, India

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Article history: Received 29 September 2015 Received in revised form 9 February 2016 Accepted 15 February 2016 Available online xxx Keywords: Mucoepidermoid carcinoma Salivary gland Oncocytic Metastases

a b s t r a c t Oncocytic mucoepidermoid carcinoma (OMEC) is a very rare variant of mucoepidermoid carcinoma, which is usually described in literature as a low-grade cystic lesion. High-grade lesions have also been described but a thorough search of literature did not show any reported case with lymph node metastasis. Here, we present the case of a 65-year-old male with an asymptomatic slow growing neck mass for nine months. The resected tumor revealed a circumscribed mass with solid and cystic areas with large cervical lymph nodes. Histopathological examination showed oncocytic cell predominance with areas of squamoid and mucinous differentiation. Four lymph nodes were found to be positive. Periodic acidSchiff, mucicarmine and alcian blue stains were positive. P63, which has recently been suggested as a reliable marker for OMEC, showed diffuse strong positivity. This variant is important because of its rarity and high chances of misdiagnosis. The use of ancillary technique is important in the diagnosis of this rare entity. © 2016 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽

1. Introduction Oncocytic neoplasms comprise approximately 1% of parotid neoplasms, majority of which are benign with low malignant rates (∼11%) [1]. Lesions with oncocytes in salivary glands have a wide range of differential diagnosis, one of them being the very rare oncocytic mucoepidermoid carcinoma. It is important to diagnose this rare entity as most lesions with oncocytes are benign and thus the diagnosis becomes important in management and follow-up of the patient. Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor in all age groups. Multiple histologic variants have been described in literature. The rare oncocytic variant of MEC has been described in <50 cases in literature, most of which were low-grade. Although high-grade cases have been reported, we did not find any report with lymph node metastasis in the English literature.

夽 Asian AOMS: Asian Association of Oral and Maxillofacial Surgeons; ASOMP: Asian Society of Oral and Maxillofacial Pathology; JSOP: Japanese Society of Oral Pathology; JSOMS: Japanese Society of Oral and Maxillofacial Surgeons; JSOM: Japanese Society of Oral Medicine; JAMI: Japanese Academy of Maxillofacial Implants. ∗ Corresponding author at: Department of Pathology, University College of Medical Sciences & GTB Hospital, University of Delhi, Shahdara, Delhi 110095, India. Tel.: +91 11 22592971x5612; fax: +91 11 22590495. E-mail address: [email protected] (S. Sharma).

OMEC is defined as a tumor with features of mucoepidermoid carcinoma with predominance of oncocytes (taken as at least 50% by some authors) [2]. OMEC is not difficult to diagnose when there are definite areas of typical MEC, but it becomes difficult when typical MEC areas are lacking and oncocytes almost predominate the lesion [2,3]. Various special stains are used to aid in diagnosis; recent studies have highlighted the importance of p63 in the diagnosis of this entity. 2. Case report A 65-year-old male presented with complaints of painless swelling below left ear for nine months with accelerated growth in the last three months. He had no other relevant history. On examination, a single, globular, non-tender, firm, non-mobile mass measuring 6.4 cm × 4 cm was found in the parotid region pushing the earlobes upwards and forwards. The overlying skin was free and unremarkable. There was no evidence of facial nerve involvement. CECT scan reported 4.4 cm × 3.8 cm heterogeneously enhancing mass in left parotid gland involving both superficial and deep lobes and cervical lymphadenopathy suggestive of malignant etiology with clinical stage T3N2bMx. FNAC performed at an outside institution suggested a highgrade malignant salivary gland tumor with a possibility of carcinoma ex-pleomorphic adenoma. However, no slides were available for our review. The patient underwent an uneventful left total parotidectomy with modified radical neck dissection

http://dx.doi.org/10.1016/j.ajoms.2016.02.006 2212-5558/© 2016 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽

Please cite this article in press as: Murry WT, et al. Oncocytic mucoepidermoid carcinoma with lymph node metastasis: A report of a rare case with review of literature. J Oral Maxillofac Surg Med Pathol (2016), http://dx.doi.org/10.1016/j.ajoms.2016.02.006

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and centrally placed nuclei with small prominent eosinophillic nucleoli (Fig. 3). Nuclear atypia and mitosis were not seen. Lymphovascular invasion was noted, however, no evidence of perineural invasion was identified. Normal salivary gland tissue surrounding the tumor was seen surrounding the tumor in one of the sections. Mucicarmine was positive in the intraluminal secretions as well as in the scattered mucous cells interspersed with the oncocytes (Fig. 4A). PAS with and without diastase also showed similar positivity (Fig. 4B). The secretions also showed alcian blue positivity (Fig. 4C). Intense blue granular cytoplasm was noted with PTAH stain (Fig. 4D). Cytokeratin 7 was positive while smooth muscle actin was negative in tumor cells (Fig. 5A and B). Immunohistochemistry for p63 showed diffuse strong nuclear positivity (Fig. 5C). Thus, a histopathological diagnosis of OMEC was made. Fig. 1. Nests and trabeculae of oncocytic cells, with intraluminal secretions lined by oncocytic cells with foci of squamoid nest. H&E 100×.

Type II. We received the specimen in 10% buffered formaldehyde solution. On gross examination, the left parotid gland measured 7.7 cm × 4.5 cm × 3 cm, was firm to hard, globular with bosselated surface. On cut section, a partly encapsulated, well-circumscribed tumor was seen replacing most of the normal parotid gland. The tumor was variegated with cystic and solid areas. A large cyst measuring 4 cm × 4 cm filled with mucoid material was present along with two solid nodules each measuring around 2 cm × 1 cm. A thin rim of normal salivary tissue was also identified at the periphery. Two other specimens labeled jugulodigastric and cervical lymph nodes measuring 3.5 cm × 3 cm × 1.5 cm and 4.4 cm × 2.5 cm × 2 cm respectively were also received. Total six lymph nodes were identified in the specimens. On light microscopy, a well-circumscribed tumor consisting of more than 50% oncocytic cells showing solid and microcystic areas was seen (Fig. 1). Focally, the tumor was seen infiltrating into surrounding tissue. Most of the tumor was surrounded by a fibrocollagenous capsule of variable thickness. The tumor cells were arranged in nests, trabeculae and acinar pattern separated by strands of fibrocollagenous stroma showing variable degree of chronic inflammation. Few areas of necrosis were noted. Variably sized cysts and acini filled with secretions, and lined by oncocytic cells interspersed with mucous cells, were noted (Figs. 2 and 3). Nests of squamous cells showing typical cobblestone appearance with evident intercellular bridging were identified focally (Fig. 1). The oncocytic cells were round to polygonal, had low nuclear cytoplasmic ratio, with abundant granular eosinophillic cytoplasm

Fig. 2. Oncocytic cells (left) with nests of squamoid cells (right) showing typical cobblestone appearance. H&E 400×.

Fig. 3. High-power view of oncocytic cells showing granular cytoplasm. H&E 1000×.

This tumor was graded according to Brandwein as Grade III as three out of eight parameters (lymphatic invasion, necrosis and infiltrative margins) were present [4]. Six lymph nodes were identified out of which four of them were positive for tumor. The microscopic features were similar to the primary tumor in parotid.

3. Discussion Diagnosis of MEC is based on identification of mucinous, intermediate and epidermoid cells. Apart from these, a plethora of variants have been described, like clear cell, spindle cell, sclerosing, sclerosing with eosinophilia, goblet cell, psammomatous, sebaceous variants, etc. The oncocytic variant has predominance of oncocytes. Parotid is the favored site with 75% of the reported cases. Three cases of submandibular, two from palate, one sublingual, and four minor salivary glands have also been reported [2,5–10]. OMEC has also been described in the bronchus, trachea and lacrimal glands [11–14]. Oncocytic change is an age-related degenerative change, almost universally found in senile individuals >70 years with or without salivary gland pathology in varying percentages [15]. The mean age of presentation of OMEC is 57 years, comparable to MEC, which peaks at the fourth decade [4]. Although it has been reported in a patient as young as 9 years, it is a disease of older individuals with 72% occurring in more than or equal to 50 years of age [16]. It has no predilection to either of the sex. Our patient was a 65-year-old male. Size of the tumor ranges from 0.7 cm to 6.5 cm with a mean of 2.7 cm [15,17]. Our case was larger in size, possibly due to accelerated growth owing to high-grade nature. 51% of the reported cases

Please cite this article in press as: Murry WT, et al. Oncocytic mucoepidermoid carcinoma with lymph node metastasis: A report of a rare case with review of literature. J Oral Maxillofac Surg Med Pathol (2016), http://dx.doi.org/10.1016/j.ajoms.2016.02.006

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Fig. 4. Special stains performed. (A) Secretions positive with mucicarmine stain, 400×. (B) Secretions positive with PAS stain, 400×. (C) Secretions positive with alcian blue, 400×. (D) Cytoplasmic granules positive with PTAH, 400×.

Fig. 5. Immunohistochemistry results. (A) Tumor cells positive for cytokeratin, 100×. (B) Negative staining for smooth muscle actin, 100×. (C) Nuclear staining with P63, 400×.

Please cite this article in press as: Murry WT, et al. Oncocytic mucoepidermoid carcinoma with lymph node metastasis: A report of a rare case with review of literature. J Oral Maxillofac Surg Med Pathol (2016), http://dx.doi.org/10.1016/j.ajoms.2016.02.006

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Table 1 Comparison of light microscopic features, special stains and immunohistochemistry of various differentials of oncocytic mucoepidermoid carcinoma.

OMEC

Nodular oncocytosis

Oncocytoma

Oncocytic carcinoma

Oncocytic cystadenoma

Warthin’s tumor Mucin-rich variant of SDC PA with oncocytic change Acinic cell tumor

Myoepithelioma

Metastatic RCC

Morphology

Mucicarmine

PAS

Alcian blue

P63

PTAH

SMA

- Oncocytes with mucinous, intermediate and epidermoid cells. - Mucin. - Diffuse oncocytic metaplastic process - Atrophy of surrounding parenchyma. - Lobular architecture preserved - Well circumscribed. - Oncocytes arranged in solid sheets, nests and cords. - Typical epitheloid and mucinous cells absent. - Cystic change absent. - Cytologically malignant oncocytes with nuclear atypia, anaplasia and mitosis - Infiltrative margins, lymphovascular and perineural invasions. - Oncocytes lining the cystic structures do not contain mucous cells. - Does not show epidermoid differentiation. - Lymphoid stroma along with oncocytes.a - Large pools of extracellular mucin with floating tumor cells. - Typical areas of myxoid or chondromyxoid stroma. - Microcystic pattern with basophilic granular cytoplasm and basally located nuclei which may look like oncocytes. - Solid, reticular, myxoid pattern - Plasmacytoid, spindle, clear, oncocytic cells - Mucoid or hyaline stroma - Compact-alveolar or nested architectural pattern

+

+

+

Diffuse strong nuclear +

+









Peripheral +

+









Peripheral +

+









Peripheral +

+



+

+

+



+



+ +

+ +

+ ±

− −

+ −

− −

+ −

+ +

+ −

+ +

+ −

+/− −







+

?+

+



+





+



PAS – periodic acid-Schiff; PTAH – phosphotungstic acid-hematoxylin; SMA – smooth muscle actin; OMEC – oncocytic variant of mucoepidermoid carcinoma; SDC – salivary duct carcinoma; RCC – renal cell carcinoma; PA – pleomorphic adenoma. a With prominent oncocytic change, squamous and mucous metaplasia, it may mimic OMEC and vice versa, OMEC when it is bilayered may mimic such type of Warthin. But OMEC shows more complex stratification with intermediate cells below mucous cells and oncocytes. P63 can be helpful in such cases.

were cystic grossly, 31% were solid and the rest were of mixed type. Our case too had both solid and cystic areas. On light microscopy, the lesions are largely composed of oncocytes comprising of 50% or more of the tumor mass. The arrangement of the cells is varied ranging from solid sheets and nests of oncocytes to mucin-filled cysts lined by oncocytes. Squamoid cells are usually in nests with cobblestone appearance, and mucinous cells are often interspersed in oncocytic clusters or cysts linings. Oncocytes are large polygonal cells with abundant granular cytoplasm, central vesicular nuclei and eosinophilic nucleoli. Mitosis is usually negligible and not found in any of the OMECs, including this case, except in one case report [16]. Similarly, nuclear atypia is rare, although few cases of moderate nuclear atypia have been described. Nuclear atypia was not observed in this case as well. Although oncocytes are easily recognizable on light microscopy, phosphotungstic acid-hematoxylin (PTAH) stain and/or antimitochondrial antibody can be used to demonstrate mitochondria in the oncocytes for confirmation. In our case, the oncocytes showed intense blue granular cytoplasm with PTAH stain. Recently, p63 has been suggested as a useful ancillary technique in differential diagnosis of OMEC, which shows diffuse nuclear positivity [2]. P63 is known to be positive in MEC. P63 showed diffuse nuclear positivity in our case too, thus helping in clinching the diagnosis. Table 1 compares the light microscopic findings, special stains and immunohistochemistry of various differential diagnosis of oncocytic mucoepidermoid carcinoma. In our case, the classic histomorphology along with positive staining for mucicarmine, PAS, alcian blue and PTAH, and diffuse nuclear positivity for p63, facilitated the diagnosis of an oncocytic variant of mucoepidermoid carcinoma. Most of the reported cases were well circumscribed with no local invasion or distant metastasis, except in few cases [2,16]. All reported cases were free of lymph node metastasis. This is the first case with lymph node metastasis. OMEC usually follows indolent behavior regardless of the histologic type [16,18].

MAML2 rearrangement, which is well known with MEC, can be used to differentiate OMEC from its other oncocytic mimics. Gracia et al. used fluorescent in situ hybridization (FISH) for detection of MAML2 rearrangement in OMEC and found it to be a useful ancillary test for diagnosis [16]. We could not perform this test due to nonavailability. The differential diagnosis of oncocytic tumors is wide, as oncocytic change can be found in any tumor as well as in nonpathological tissues as an age-related change. In a tumor composed of almost entirely of oncocytes, a combination of all these tests including PTAH, p63 and MAML2 rearrangement can be used to diagnose OMEC [3]. 4. Conclusion It is important to diagnose OMEC from other oncocytic lesions, as most other oncocytic lesions are benign. OMECs are usually indolent but can be high-grade with metastasis even to lymph nodes as in this case. Ancillary techniques are important in differential diagnosis. Financial support No financial support of any form has been taken from any agency for this study. Conflict of interest No conflict of interest. References [1] Oghan F, Apuhan T, Guvey A. Rare malignant tumors of the parotid glands: oncocytic neoplasms. In: Kummoona R, editor. Neck dissection – clinical application and recent advances. Croatia: InTech; 2012. p. 137–48.

Please cite this article in press as: Murry WT, et al. Oncocytic mucoepidermoid carcinoma with lymph node metastasis: A report of a rare case with review of literature. J Oral Maxillofac Surg Med Pathol (2016), http://dx.doi.org/10.1016/j.ajoms.2016.02.006

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Please cite this article in press as: Murry WT, et al. Oncocytic mucoepidermoid carcinoma with lymph node metastasis: A report of a rare case with review of literature. J Oral Maxillofac Surg Med Pathol (2016), http://dx.doi.org/10.1016/j.ajoms.2016.02.006