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CASE REPORT
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Gnathic variant of primary adenoid cystic carcinoma: A unique case report


 Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Kolkata, West Bengal, India

Date of Submission15-Jan-2020
Date of Decision29-Aug-2020
Date of Acceptance11-Apr-2021
Date of Web Publication07-Feb-2022

Correspondence Address:
Sayani Shome,
Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, 157/F Nilgunj Road, Panihati, Kolkata - 700 114, West Bengal
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_56_20

 > Abstract 


Adenoid Cystic Carcinoma (AdCC) is an uncommon malignant epithelial salivary gland neoplasm, which is indolent yet persistent. Intraosseous /central variant of AdCC of the jaw is poorly understood owing to its innocuous clinical presentation thus posing a diagnostic challenge. AdCC is characterized by perineural invasion, late distant metastasis and a high recurrence rate , thus having a major effect on the mortality and morbidity rate. It is often diagnosed at an advanced stage which is chiefly achieved through histological examination and complete clinic-radiological work up. A clinical case of an intraosseous variant of AdCC, involving the mandible of a 49 year old male patient is discussed herewith, encompassing the entire spectrum of clinicopathological, radiological and treatment modalities rendered.

Keywords: Adenoid cystic carcinoma, intraosseous, malignant salivary gland neoplasm



How to cite this URL:
Shome S, Mallick A, Kundu S, Gayen S. Gnathic variant of primary adenoid cystic carcinoma: A unique case report. J Can Res Ther [Epub ahead of print] [cited 2022 Nov 29]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=337358




 > Introduction Top


Salivary gland neoplasms are heterogeneous groups of diseases possessing a diagnostic challenge.[1] Adenoid cystic carcinoma (AdCC) is one such rare, slowly enlarging, but aggressive tumor which comprises only 1%–2% of head-and-neck malignancies[2] and 6%–10% of all epithelial salivary gland neoplasms.[3] The occurrence of the intraosseous variant is extremely unusual, accounting for <0.4% of all salivary carcinomas.[4] It was first described by Theodor Billroth as “Cylindroma” in 1859 and later as “Basiloma” by Krompecher in 1908.[5] Finally, the widely used term “Adenoid Cystic Carcinoma” was coined by Ewing in 1954.[5]

Various literatures suggested that intraosseous variants of the salivary gland neoplasms may arise due to entrapment of retromolar mucous glands during embryonic development of the mandible, close approximation of submandibular and sublingual cortex of the mandible, embryologic evagination of residues of submandibular and sublingual glands, or neoplastic transformation of the remnants of odontogenic epithelium/cyst-lining/sinus lining.[4],[5]

AdCC reveals a mild preponderance for middle-aged females between 5th and 6th decades of life; however, the central variant exhibits no such predilection.[2],[5] These are prevalent in minor salivary glands and rarely occur in the major salivary glands,[6] with the intraosseous variant most commonly occupying the posterior mandible followed by the maxilla.[4] Clinically, it appears as a slowly enlarging mass often associated with dull pain and surface ulceration exhibiting a relentless growth pattern and can lead to a clinically evident diffuse swelling and destruction of the cortical plates of the jaw when involved centrally.[2],[3]

Radiographically, intraosseous AdCC is characterized by the presence of unilocular or multilocular radiolucent lesions are associated with peripheral bone destruction and poor peripheral demarcation often mimicking odontogenic cysts or tumors or other malignant jaw tumors.[7],[8] However, computed tomography (CT) and magnetic resonance imaging can be used to detect the peripheral spread of the tumor and fluorodeoxyglucose positron emission tomography to delineate distant metastasis.[9],[10]

AdCC microscopically consists of ductal and myoepithelial cells arranged in a variety of architectural patterns such as cribriform, tubular, and solid pattern. The cribriform/cylindromatous variant of AdCC is the most frequent and classical subtype which is composed of islands of basaloid cells interspersed with variably sized cylindrical pseudocystic spaces fused with a mucoid/hyalinized material giving a “swiss-cheese”/“honey-comb” appearance. The tubular variant consists of basaloid cells lining apparent ductal spaces or tubular areas amidst a variable amount of hyalinized stroma. Large aggregates of sheets of tumor cells with very few luminal spaces represent the solid variant of AdCC which also shows extensive apoptosis, cellular pleomorphism, focal comedo necrosis, and mitotic activity which are rarely found in the other variants.[11]

The biphasic differentiation of AdCC can be immunohistochemically confirmed by positive staining with α-smooth muscle actin (α-SMA), S-100, Vimentin, smooth muscle heavy chain as well as immunoreactivity for carcinoembryonic antigen, epithelial membrane antigen , and cytokeratin (CK).[8] The tumor also may show a positive reaction with C-kit (CD 117), CD 34, and glial fibrillary acidic protein.[6] The SRY-related HMG Box (Sox) 10 is a well-established marker for those cells which are differentiated from neural crest origin, such as myoepithelial cells.[12]

AdCC is best treated by surgical resection with a negative safety margin along with adjuvant postoperative radiotherapy. Neck dissection is performed in case of clinically or radiographically positive lymph node metastasis. Chemotherapy can be used as a palliation to inhibit distant metastasis.[3],[4],[10]

AdCC classically shows distinct perineural invasion, lymph node metastasis, and frequent distant metastasis.[3] The 5-year survival rate is approximately from 77% to 82% in an average which declines gradually.[6] At the end of 10 years, survival rate remains about 60%–68% which decreases to 35%–52% by 20 years.[6]

A rare case of intraosseous variant of AdCC of the mandible is discussed here with relevant clinic-pathological, radiological, and histopathological findings.


 > Case Report Top


A 49-year-old male patient reported to the Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Panihati, Kolkata, with the chief complaint of a painless, hard swelling on the lower right back teeth region which gradually expanded since 2–2.5 months after extraction of regional mobile teeth.

Extraorally, there was the presence of a diffuse, nontender, bony hard swelling involving the right side of the body of the mandible rendering an obvious facial asymmetry [Figure 1]. There was expansion of the lower border of the mandible on the right side along with ipsilateral submandibular lymphadenopathy on palpation. Overlying skin appeared normal and signs of paresthesia were elicited over the right half of the chin and lower lip.
Figure 1: Extra-oral clinical photographs (a and b) showing diffuse swelling involving the right lower third of face

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Intraoral examination revealed the presence of an ill-defined, nontender, bony hard swelling along with expansion of the buccal and lingual cortical plates in relation to 41–48 [Figure 2]. 41, 42, 46, 47, and 48 were missing. Overlying mucosa appeared normal, except for racial pigmentation focci.
Figure 2: Intra-oral clinical photograph showing presence of a swelling involving the right lower posterior dento-alveolar region

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The patient was hypertensive and type II diabetic, which was controlled by routine medications. His past surgical history, personal history, and family history were noncontributory.

Orthopantomogram (OPG) revealed irregular destructive radiolucent lesion involving the right side of the body of the mandible along with loss of interdental bone around the regional teeth. Computed tomography (CT) view exhibited ill defined, hypodense area with the expansion of buccal and lingual cortical plates on the mandibular right dentoalveolar region. Cone-beam computed tomography (CBCT) showed massive destruction and perforation of the right half of the parasymphysis and body and alveolar process of the mandible while the lower border and angle region were intact [Figure 3].
Figure 3: Orthopantomogram, CT and CB-CT images (a-c) showing the presence of a destructive lesion involving the right half of the parasymphysis, body and alveolar process of the mandible

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Keeping the clinical and radiological features in mind, a provisional diagnosis of intraosseousmalignant neoplasm was made.

Incisional biopsy was performed from the representative site after obtaining informed consent from the patient and the tissue was further processed for microscopic evaluation.

Sections stained with hematoxylin and eosin revealed the presence of islands of actively proliferating neoplastic basaloid epithelial cells arranged in solid and microcystic cribriform patterns resembling “Swiss Cheese” like appearance within a fibrovascular connective tissue stroma. The tumor cells were small and exhibited large deeply basophilic, hyperchromatic, and uniform nuclei [Figure 4]. Aggregates of tumor cells were observed within the lumen of the endothelium-lined capillaries and around the nerve bundles which were suggestive of perineural and angioinvasion [Figure 5]. Few areas with abnormal mitotic figures were also seen. The overall histopathologic features were suggestive of intraosseous variant of AdCC.
Figure 4: Low-power photomicrograph (H and E, ×10) showing islands of basaloid cells in solid and cribriform pattern arranged in fibro-vascular connective tissue stroma

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Figure 5: High-power photomicrographs (H and E, ×40) (a and b) showing perineural invasion and angio-invasion of the neoplastic cells

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Immunohistochemistry was performed to confirm tumor cell lineage from salivary gland origin where Sox 10, CK-7, S-100, and α-SMA were immunoreactive and CD117(C-kit) and smooth muscle myosin were immunonegative [Figure 6], [Figure 7], [Figure 8].
Figure 6: Low and high-power photomicrographs (×10, ×40) (a and b) showing Sox 10 immunopositivity

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Figure 7: Low-power photomicrographs (×10) (a and b) showing CK-7 and S-100 immunopositivity

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Figure 8: High-power photomicrograph (×40) showing α-SMA immunopositivity

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The histopathological features of the present case confirmed the salivary glandular origin, precisely the luminal and myoepithelial cell phenotype of the tumor and it was diagnosed as “High–grade Intraosseous Adenoid Cystic Carcinoma”. The patient was referred to Departmen of Oral and Maxillofacial Surgery for further surgical treatment and management, but the patient refused to undergo surgery and denied to contact us further. Hence, the case could not be followed up postoperatively and distant metastasis could not be ruled out.


 > Discussion Top


AdCC is a complex salivary malignancy of glandular epithelial and myoepithelial origin. Intraosseous salivary gland neoplasms are extremely rare with intraosseous variant of mucoepidermoid carcinoma being the most common among them followed by the central variant of AdCC.[6],[8] AdCC is a rarely encountered neoplasm presenting about 0.5% of all the malignancies.[10]

Histogenesis of malignant salivary gland neoplasms are quite controversial and different theories have been put forward explaining it, the most widely accepted of them being the basal reserve cell theory and semipluripotent bicellular reserve cell theory.[13]

The patient under discussion was a 49-year-old male having a diffuse, nontender, and bony hard swelling with the expansion of buccal and lingual cortical plates with ipsilateral submandibular lymphadenopathy. These clinical features were in corroboration with the clinical observations reported by the authors of different studies.[4],[5],[8]

The radiological features as depicted through the OPG, CT, and CBCT scan revealed massive irregular destruction of the mandible with expansion of buccal and lingual cortical plates. These features were thus very suggestive of intraosseous AdCC as mentioned by the previous authors.[2],[4],[8]

Brookstone and Huvos proposed a staging system for the central salivary gland neoplasm:[14]

  • Stage I: Lesions located within undisturbed, intact cortical bone and overlying periosteum without any sign of cortical expansion
  • Stage II: Lesions with some degrees of expansion but intact cortical bone
  • Stage III: Lesion characterized by cortical perforation, breakdown of overlying periosteum, or nodal metastatic spread.


The referred case could be categorized under stage III of the above-mentioned staging system based on its radiographic findings.

Histologically, AdCC can present either as a solid, tubular, or cribriform pattern or a mixture of them. The solid variant is the least common and most aggressive one with 100% recurrence rate and worst prognosis whereas the tubular and cribriform patterns have a better prognosis with a recurrence rate of 50%–80%.[5]

Gnathic involvement of primary AdCC clinically and radiologically can mimic a wide array of intraosseous odontogenic or nonodontogenic malignant neoplasms.[7],[9],[14] Although histopathology is of prime importance for proper diagnosis of AdCC, it needs to be differentiated from similar histopathological entities such as polymorphous low-grade adenocarcinoma (PLGA), basal cell adenocarcinoma (Bcad. C), and basaloid squamous cell carcinoma (BSCC).[11]

PLGA consists of uniform tumor cells with cytologically bland, round, oval, or vesicular nuclei and eosinophilic cytoplasm rather than angular, hyperchromatic nuclei and relatively higher mitotic index (Ki-67 is 10x higher in AdCC than PLGA) as seen in AdCC.[11] In PLGA perineural invasion is seen as whirling “targetoid pattern” of single cord of cells which is absent in AdCC.[3] The presence of basaloid cells both in BCAd. C and solid AdCC creates difficulty in diagnosis. However, the presence of peripheral palisading and foci of squamous metaplasia suggests the diagnosis of BSCC instead of AdCC.[3] BSCC is a distinct, high-grade malignant tumor of the hypopharynx, base of the tongue, and supraglottic region where basaloid cells are arranged in a lobular pattern with multiple attachments to the overlying epithelium.[11] The most striking feature is the absence of ductal and myoepithelial components which is an obvious finding in AdCC.[11]

Histological grading based on the degree of the solid pattern was proposed by Szanto et al. which stated that tumors with tubular and cribriform areas with no solid component is considered to be Grade I. Grade II consisted of pure or mixed cribriform pattern (>30% solid areas) and the predominantly solid pattern was classified as Grade III. The admixture of solid and microcystic cribriform patterns in the present case strongly mimicked the feature of a Grade II AdCC.[15]

The simultaneous presence of the epithelial and myoepithelial cells in the present case was demonstrated by positive immunoreactivity with CK 7, S 100, α SMA, and Sox 10. C kit (CD 117), smooth muscle myosin however were immunonegative. The salivary glandular origin, precisely the luminal and myoepithelial phenotype of the tumor was thus clearly spelled by the histochemical staining.

A diagnostic criteria put forward by Batsakis et al. in 1979 for the confirmative diagnosis of a central salivary gland neoplasm comprised radiographic evidence of osteolysis, maintenance of cortical integrity, presence of intact mucous membrane overlying the lesion, absence of any primary tumor within a major/minor salivary gland and histological confirmation of the architectural and morphological findings of salivary gland tumor.[4] The present case fulfilled all the criteria stated by Batsakis and was thus established as a “Central variant of high-grade Adenoid Cystic Carcinoma.”

The management of AdCC is dependent on certain factors such as cell type, degree of differentiation, site, size, and location of the primary lesion, status of the lymph node, and the presence of bone involvement.[16] The “Gold standard” therapy for AdCC is surgical resection with negative safety margins along with adjunctive postoperative radiotherapy as AdCC is known to be radiosensitive.[4],[6],[10]

The prognosis of AdCC is dependent on several factors such as the primary site of the tumor, the presence of perineural invasion, lymph node metastasis, distant metastasis, involvement of the adjacent structures, clinical stage of the disease, histopathological variant of the tumor, treatment modality employed and positive margins of surgical excision or tumor DNA ploidy.[6],[16]

Appropriate diagnosis and postoperative follow-ups are very important to prevent recurrences and distant metastasis of this neoplasm.

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.

Acknowledgment

Authors are indebted to Prof. Dr. R R Paul, Prof. Dr. Mousumi Pal, Prof. Dr. Sekhar Chakrabarty and the entire Department of Oral and Maxillofacial Pathology, GNIDSR for all the academic inputs for publication of this case report.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]



 

 
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