|Ahead of print publication
Unusual presentation of cribriform adenocarcinoma of salivary glands: A case report
Noura M Kamal1, Mohamed F Nahla2, Sarah A M. Mahmoud3
1 Oral and Maxillofacial Pathology, Faculty of Dentistry, Cairo University; School of Dentistry, NewGiza University, Giza, Egypt
2 Oral and Maxillofacial Surgery Resident, Faculty of Dentistry, Cairo University, Egypt
3 Oral and Maxillofacial Pathology, Faculty of Dentistry, Cairo University, Egypt
|Date of Submission||18-Feb-2022|
|Date of Decision||18-Jun-2022|
|Date of Acceptance||04-Jul-2022|
|Date of Web Publication||01-Nov-2022|
Noura M Kamal,
79 Khatem El-Morsaleen Street, Omranya
Source of Support: None, Conflict of Interest: None
According to the last edition of the World Health Organization classification, cribriform adenocarcinoma of salivary glands (CASGs) was considered a variant of polymorphus adenocarcinoma although many authors proposed CASG as a distinct neoplasm. The aim of this study was to report an unusual presentation of CASG in the buccal mucosa of a 63-year-old male patient that showed signs of encapsulation and no evidence of lymph node metastasis. The lesion was composed of lobules of tumoral cells arranged in solid nests, sheets, papillary, and cribriform or glomeruloid patterns. Most of the peripheral cells show palisaded arrangement with peripheral clefting from the adjacent stroma. Surgical resection of the lesion was done and further neck dissection was recommended.
Keywords: Buccal mucosa, cribriform adenocarcinoma, head and neck neoplasms, salivary glands
| > Introduction|| |
Cribriform adenocarcinoma of salivary glands (CASGs) was firstly described by Michal et al., 1999. In the fourth edition of the World Health Organization classification, CASG was considered a variant of polymorphus adenocarcinoma (PAC) due to the similarity between them in the cellular appearance and the pattern of arrangement of the cells. Many authors opposed this assumption and proposed CASG as a single entity due to its difference from PAC in the clinicopathological aspect. Regional lymph node metastasis in CASG was estimated to be more than 60%. To our knowledge, all the reported cases in the English literature showed grossly an infiltrative growth pattern with neither hemorrhage nor necrosis. In the following report, we present a case of capsulated CASG in the buccal mucosa with no evidence of lymph node metastasis at the time of the diagnosis.
| > Case Report|| |
A 63-years-old male patient presented to the Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Cairo University, complaining of swelling in the buccal mucosa, which was of 6 × 5 × 4 cm size. The swelling first appeared 2 years ago and rapidly enlarged during the past 3 months with slight pain sensation, but without bleeding or difficulty in eating or speaking. The patient had a stroke 2.5 years ago and was on anticoagulant medications (Jasprin). He was also Type-2 controlled diabetic with fasting blood sugar level of 89 mg/dL and random blood sugar level of 102 mg/dL, and the patient stated that he is taking his medications regularly.
Intraoral examination revealed a well-circumscribed normal-colored mucosa swelling in the buccal mucosa opposite to the upper right premolar area [Figure 1]a, which was soft in consistency. The regional lymph nodes were not palpable nor tender. Radiographic examination of the area showed no bone involvement.
|Figure 1: A photograph showing a well-circumscribed normal-colored mucosa swelling in the buccal mucosa opposite to the upper right premolar area (a). A superficial incision was made in the covering mucosa revealing the capsulated nature of the lesion (b)|
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The patient was tested for INR and other coagulation lab tests (prothrombin time [PT] and activated partial thromboplastin time [aPTT]) and was found to be within normal reference range before being biopsied. The area was disinfected with betadine, then ring block anesthesia was administrated to the area; not inside the lesion to avoid its distortion. A superficial incision was made in the covering mucosa; avoiding cutting through the lesion [Figure 1]b. The lesion was separated from the overlying mucosa using blunt scissors and mucoperiosteal elevator. Then lesion was held by Allis forceps to facilitate its separation from the underlying muscle. Worthy to mention, the lesion had a capsule, which facilitates its separation from the overlying mucosa and the underlying muscle. The wound was sutured with nonabsorbable silk 4.0.
The biopsy was sent to Oral and Maxillofacial Pathology Department, Faculty of Dentistry, Cairo University for histopathological examination, which was a reddish soft capsulated mass with several hemorrhagic spots [Figure 2]a. The biopsy was sectioned [Figure 2]b and processed for examination, which revealed a capsulated tumor [Figure 3]a, which consisted of lobules of proliferating cells separated by thin fibrous septa and pools of hemorrhage [Figure 3]b. Tumoral cells grew in several patterns; mainly, solid nests and sheets [Figure 3]c. In some areas, papillary, cribriform, and glomeruloid patterns were evident [Figure 3]d. Most of the peripheral cells were arranged in a palisaded manner and showed peripheral clefting from the adjacent stroma or the remaining cells. The proliferating cells had eosinophilic cytoplasm, which was clear in some cells, and the peculiar pale “Orphan-Annie” nuclear appearance [Figure 4]. There was no nuclear atypia nor perineural invasion but necrosis was evident. Immunohistochemical staining with thyroid transcription factor -1 (TTF-1) was performed to distinguish it from papillary thyroid carcinoma (PTC), which showed negative reaction and confirmed the diagnosis of cribriform adenocarcinoma of salivary gland [Figure 5].
|Figure 2: A photomicrograph of the excisional biopsy showing reddish soft capsulated mass (a). The tumor appears to be solid in cut sections with several hemorrhagic spots (b)|
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|Figure 3: A photomicrograph showing a capsulated tumor (arrowheads) (a) which consisted of lobules of proliferating cells separated by thin fibrous septa and pools of hemorrhage (black arrows) (b). Tumoral cells growing in solid nests and sheets (c). In some areas, papillary, cribriform, and glomeruloid patterns were evident (black arrows) (d) (hematoxylin-eosin, original magnification A. B, C × 40 and D × 100)|
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|Figure 4: A photomicrograph showing the peculiar pale “Orphan-Annie” nuclear appearance of the tumor cells (black arrows) (hematoxylin-eosin, original magnification A × 400 and B × 600)|
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|Figure 5: A photomicrograph showing negative immunohistochemical staining with TTF-1 (original magnification × 200)|
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Ten days after the surgery [Figure 6], the patient came for suture removal, then he was referred to National Cancer Institute, Cairo University for regional lymph node dissection to complete his treatment according to the guidelines.
| > Discussion|| |
Michal et al., 1999 firstly described CASG as a distinct entity from PAC and called it “cribriform adenocarcinoma of the tongue;” as all the eight cases they collected occurred in the tongue. They based their assumption on the difference between CASG and PAC in the clinicopathological behavior; where most of the cases were infiltrative and showed regional lymph node metastasis at the time of the diagnosis. Moreover, CASG has a distinctive histopathological features that resemble papillary thyroid carcinoma, which raised the presumption that the origin of CASG may be lingual thyroglossal duct anlage. This presumption was prohibited when cases occurred in locations other than the tongue such as soft palate, lip, epiglottis, tonsils, and floor of the mouth. Thus, the lesion was renamed cribriform adenocarcinoma of minor salivary glands. Later, cases in major salivary glands were reported, therefore the term “cribriform adenocarcinoma of salivary glands” was suggested.
Weinreb et al., 2014 screened genetic rearrangements in 60 cases of PAC and CASG using fluorescence in situ hybridization (FISH), which revealed Protein kinase D1 (PRKD1)-3 rearrangements in CASG, with 80% of the cases showing PRDK1 translocation. On the other hand, PAC mostly showed hotspot mutation in the same gene. Xu et al., 2020 performed FISH on 37 cases of CASG and PAC and reached the same results as Weinreb et al., 2014. Furthermore, they found that the hotspot mutation in PRDK1 was not specific to PAC as it was present in CASG cases as well. These findings raised the debate whether CASG and PAC are of the same entity or not.
Contrary to our case, CASG was described in the literature as an uncapsulated tumor with infiltrative borders. Furthermore, it has no areas of necrosis or hemorrhage. The histopathological features of CASG include solid, tubular, cribriform, and papillary growth of monomorphic cells, which are characterized by eosinophilic cytoplasm and pale nuclei. These nuclei are called “Orphan Annie nuclei” resembling those in papillary thyroid carcinoma, which are overlapping one another and are cleared out in the center with powdery chromatin marginated on the periphery. Peripheral palisading in solid nests is appreciated focally in many cases. A characteristic glomeruloid pattern of growth could be detected in almost all the reported cases; which is caused by artifactual clefting of the peripheral layer from the remaining tumor island.
The main differential diagnosis of CASG is PAC. However, PAC is characterized by the target-like appearance, which is the result of streaming of the narrow trabeculae of cells forming “eye of storm.” Furthermore, PAC is characterized by the single file arrangement of cells at the periphery of the lesion and lacks the glomeruloid pattern of growth as well as the Orphan Annie nuclei. Xu et al. 2020 studied the inter-observer agreement of PAC/CASG diagnosis, and found that CASG category had a lower diagnostic reproducibility. They explained this result as CASG is a relatively rare salivary gland tumor that is not universally acknowledged.
The second differential diagnosis is PTC, which has the same cellular features as CASG, but using TFF1 and thyroglobulin immunohistochemistry, which are the only useful markers to distinguish between the two entities. However, adenoid cystic carcinoma (ACC) is different both cytologically and clinically, it should be included in the differential diagnosis of CASG. ACC is a biphasic tumor with P63 stains on the abluminal cells. Moreover, ACC cells have angular hyperchromatic nuclei with scanty cytoplasm. CASG is typically positive for myoepithelial cell markers (calponin and P63), CK7, S100, and c-kit.
Lymph node metastasis was evident at the time of the diagnosis in about 65% of the reported cases in the literature, with one case showing nodal metastasis 8 years postoperatively and one case showing cutaneous metastasis. Thus, the treatment of choice for CASG was determined by the literature to be surgical resection with neck dissection along with radiotherapy when needed. In our case, the lesion was capsulated and separated from the underlying muscle and the covering mucosa. Moreover, there was no lymph node affection, which made us wonder if neck dissection is mandatory in our case.
| > Conclusion|| |
CASG is another malignant salivary gland neoplasm with bland cytology that resemble PTC but negative for TTF1. It can occur anywhere in the oral cavity and in the major salivary glands. Its behavior varies from an infiltrative aggressive neoplasm with nodal metastasis to a totally capsulated neoplasm. Neck dissection should be limited to the cases that showed lymph node metastasis at the time of the diagnosis or cases with infiltrative growth.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given her consent for images and other clinical information to be reported in the journal. The guardian understands that her names and initials will not be published and due efforts will be made to conceal the patient's identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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