Adenosquamous carcinoma of hard palate

: A report of rare entity

R Dibin, Sibi Joseph, T Muhammad Ali, PK Alshakhir
Department of Oral and Maxillofacial Surgery, Government Dental College, Kottayam, Kerala, India

Correspondence Address:
Dr. R Dibin
Department of Oral and Maxillofacial Surgery, Government Dental College, Gandhinagar, Kottayam - 686 008, Kerala 
India

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DOI: 10.4103/jss.JSS_46_18

Abstract

Adenosquamous carcinoma of the head and neck (ADSC) is a rare and aggressive variant of squamous cell carcinoma (SCC), a locally aggressive malignancy characterized by the presence of two distinct components: A SCC and an adenocarcinoma. The purpose of this study was to report an additional rare case of adenosquamous carcinoma affecting the maxilla.

Keywords: Adenosquamous carcinoma, hard palate, oral cavity

Introduction

Adenosquamous carcinoma (ADSC) is a rare entity of the head-and-neck squamous cell carcinoma (SCC) which is characterized by mixed differentiation, with both SCC and true adenocarcinoma, as stated by the World Health Organization.^[1] It has been described in various body sites, including the uterine cervix, lung, and pancreas. The extant of ADSC of the head and neck as a distinct entity was somewhat argumentative for many years as some investigators considered it to be a high-grade mucoepidermoid carcinoma (MEC).^[2] It was first defined in the head and neck by Gerughty et al. in 1968 where it showed extreme aggressiveness and highly malignant nature, with 80% of the patients having proven metastases.^[3] The distinctly worse prognosis of ADSC as compared to MEC necessitated the separation of these entities.

Case Report

A 73-year-old male patient had been referred to our outpatient department with a chief complaint of an ulcer on hard palate noticed about 2 months before. The patient had a habit of smoking and drinking alcohol for 50 years with unremarkable medical history, had an ill-fitting maxillary complete denture. On examination, a well-defined ulcer of size 1.5 cm in diameter with everted margins extending to soft palate [Figure 1] was noted. The lesion is erythematous and oval in shape. On palpation, it is painless, indurated and no lymph nodes noted. Based on these findings, a provisional diagnosis of carcinoma of the palate was given.

Figure 1: Well-defined ulcer of size 1.5 cm in diameter with everted margins extending to soft palate Click here to view

Histopathological examination of the incisional biopsy revealed that the specimen showed dysplasia and marked hyperplasia, from which apparently an epithelial neoplasia had developed [Figure 2]a. This neoplasia was characterized by proliferation of atypical keratinocytes, forming islands of neoplastic cells infiltrating the connective tissue in the lamina propria, consistent with well-differentiated SCC [Figure 2]b. Often, in the center of these islands, keratin pearls were observed, occasionally with superposed dystrophic calcification. Furthermore in their central portions, some islands presented acantholysis producing pseudoluminae that were empty or contained cellular debris. Individually, neoplastic cells showed moderate pleomorphism, mitotic figures, multiple evident nucleoli, and marked dyskeratosis.

Figure 2: (a) Squamous superficial component in contact with the surface epithelium. (b) Squamous deep component showing keratin pearls. (c) Transitional area between the squamous component and the adenocarcinomatous component. (d) Adenocarcinomatous component Click here to view

In deeper portions of the lesion, a distinct glandular neoplasia could be observed [Figure 2]c, showing tubular structures limited by two or more layers of epithelial cells, frequently containing eosinophilic pale material [Figure 2]d. The stroma consisted of dense connective tissue with capillary blood vessels, showing diffuse mononuclear inflammatory infiltrate and, in some areas, myxoid features. The lesion margins were poorly defined, with highly infiltrative aspect in the deeper front of invasion. Peripheral portions of the specimen showed minor salivary glands apparently not affected by the tumor.

The histological hypotheses included SCC, MEC, and pleomorphic adenoma. Throughout the diagnostic process, the hypotheses of acantholytic SCC and of adenosquamous carcinoma were also included.

Histochemical staining with periodic acid–Schiff (PAS), PAS-diastase, and mucicarmine only evidenced the content of the pseudoluminal structures. Immunohistochemical and histological features rendered the diagnosis of adenosquamous carcinoma. All immunohistochemistry reactions were done using humid heat for target retrieval and streptavidin-biotin-peroxidase system for detection [Table 1] and [Figure 3]. Positive and negative controls for every antibody were also included.

Table 1: Immunohistochemistry reactions results Click here to view

Figure 3: (a) AE1/AE3: Strong positivity in squamous and adenocarcinomatous components. (b) CK5: Positive staining mainly seen in squamous component. (c) CK8/18: Positive staining mainly seen in adenocarcinomatous component. (d) CK7: Positive staining in adenocarcinomatous component. (e) CEA: Positive in adenocarcinomatous component and occasionally in squamous component. (f) Ki67: Proliferation index of approximately 10% in both components of the lesion (Source- Brazilian Dental Journal (2016) 27 (6): 781-786) Click here to view

Discussion

This case conferred very distinct clinical and microscopic features. Hence, several diagnostic hypotheses were arrived both at the clinical and histological examination. Our first clinical hypothesis was SCC as there are no other cases of adenosquamous carcinoma were reported in the hard palate with clinical findings similar to the reported one in our department. Even though in our case, the evidence of malignancy has not been found clinically, the hypothesis of MEC could be raised, since this entity occurs frequently in hard palate and in a wide range of ages. MEC, other than the classical submucosal bluish growth with fixed borders may present with several clinical appearances such as benign lesions. The benign salivary gland tumor with the highest incidence in the hard palate is certainly pleomorphic adenoma affecting young-to middle-aged adults, presenting as a painless, slow-growing mass. These are frequently located laterally in posterior hard palate and the mass usually presents regular surface.^[4] In the present case, the mass was lobulated and located centrally in the hard palate with an ulcerative component in the center.

On histopathological assessment, the initial diagnosis of the lesion was a well-differentiated SCC, since almost all features under the light microscope were consistent with that. This diagnosis was not concluded due to the deeper part of the specimen showing adenoid neoplastic components which were obviously not part of the surrounding normal minor salivary glands.

Mokhtariet al.^[5] reported a similar situation, in which the initial histopathological diagnosis was SCC and on further evaluation, the adenocarcinomatous component was noticed in metastatic cervical lymph nodes. In the same report, the diagnosis was then changed to adenosquamous carcinoma when discrete neoplastic gland-like structures were identified using specific histochemical tests. Similarly, Fonseca et al. described a lesion initially diagnosed with epithelial dysplasia with focal microinvasive well-differentiated SCC and after 12 months of follow-up a local recurrence was noted which presented with clinical appearance different from the initial lesion and it showed features consistent with adenosquamous carcinoma.^[6]

The most common site of occurrence for adenosquamous carcinoma in the head-and-neck region is larynx with 48.4% followed by the oral cavity at 30%.^[7] The most common locations in the oral cavity are the floor of the mouth, tongue, alveolus, palate, and upper lip^[8] with 6:1 male-to-female ratio.

Differential diagnosis for adenosquamous carcinoma comprises MEC, acantholytic SCC, basaloid SCC, conventional SCC, and necrotizing sialometaplasia.

The main histological differential diagnosis associated with this is MEC. In MEC gland-like structures and squamous cells tend to be intermingled while in adenosquamous carcinoma these two components are often separate and appear as two distinct areas of the tumor.^[7]Pleomorphic adenoma was also considered in the histological differential diagnosis, due to areas presenting tubular structures limited by two or more layers of cells, often presenting a mucinous content. However, this hypothesis was discarded with the observation of clear and exuberant cellular pleomorphism, mainly seen in the squamous component of the analyzed specimen.

In this case, the diagnosis of SCC seemed to be appropriate other than the two minor features observed under light microscope, which includes: acantholysis in a small number of neoplastic squamous islands forming pseudoluminae, containing or not cellular debris, and the adenocarcinomatous component, which apparently is not a part of the normal minor salivary glands of the hard palate. Hence, two other histological hypotheses were then considered: Acantholytic SCC and adenosquamous carcinoma, respectively. Acantholytic SCC is another uncommon variant of SCC, characterized by acantholysis of neoplastic squamous cells, creating pseudoluminae and a false appearance of glandular differentiation.^[8] In the present case a few areas were seen with these pseudoluminae.

Similarly, in the immunohistochemical analysis, the present case was immunopositive for carcinoembryonic antigen, excluding acantholytic SCC and emphasizing the final diagnosis of adenosquamous carcinoma.^[8] In the present case, immunohistochemical findings were crucial to reach the final diagnosis of adenosquamous carcinoma. AE1/AE3 stained positive in all neoplastic cells and in the surface epithelium, indicating the epithelial origin of the lesion [Figure 3]a. However, when considering different molecular weight keratins separately, it became obvious the dual histomorphogenesis of the neoplastic cells. That was confirmed by the positive staining for CK5 (high weight) in the squamous component [Figure 3]b and the positive staining for CK8/18 (low weight) in the adenocarcinomatous component [Figure 3]c. Staining to CK7 (low weight) was strongly positive in the cells in proximity with the luminae [Figure 3]d. The carcinoembrionic antigen is a marker largely used for the final diagnosis of adenosquamous carcinoma. The present case showed scarce positivity in the squamous component and intense positivity in the adenocarcinomatous component [Figure 3]e. The proliferation index based on Ki67 immunostaining was considered low (approximately 10%) for a malignant lesion of known aggressive behavior [Figure 3]f.

Treatment

Rather than the conventional SCC and MEC, the adeno SCC is aggressive for which treatment varies treatment varies with chemotherapy, surgery, and radiotherapy based on the site and stage of the disease. A study conducted by Keelawat et al.^[9] noted 47% of patients with local recurrence, 65% nodal metastasis and 23% distant metastasis and 42.9% died of their disease at a mean follow-up period of 24.7 months.

Conclusion

Adenosquamous carcinoma represents a diagnostic challenge due to its diverse range of clinical presentations and histological features as its adenocarcinomatous component may be, at times, difficult to identify. The recognition of the specific subtype of SCC is of great significance.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 

References

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