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Adenosquamous carcinoma of the parotid gland

Sir Adenosquamous carcinoma (ASC) is a rare malignant tumour in the head and neck region, and usually occurs as a mucosal carcinoma. The World Health Organization classification1 categorizes this tumour as a variant of squamous cell carcinoma (SCC), whereas the Armed Forces Institute of Pathology (AFIP) classification2 categorizes it as a salivary gland tumour. In the AFIP guidelines, the occurrence of ASC is limited to the minor salivary glands. Alos et al.3 suggested the following criteria for the diagnosis of ASC: (i) the most common component is usually keratinizing SCC; (ii) the second component is adenocarcinoma in the deeper portion; and (iii) severe dysplasia or carcinoma in-situ (CIS) is seen in the surface epithelium. We report here a case of ASC arising from the parotid gland. 
 
A 78-year-old Japanese woman developed rapid swelling in the right buccal region, and was admitted to our hospital 2 months later. Intraoral examination showed no mucosal lesions, but a 30 × 40-mm irregularly-shaped mass was seen in the anterior portion of the right parotid gland. Magnetic resonance imaging (MRI) showed that this mass had low intensity on T1-weighted imaging and partially high intensity on T2-weighted imaging (Figure 1A). Positron emission tomography showed no evidence of other primary lesions. Total parotidectomy was performed following a clinical diagnosis of parotid gland carcinoma. 
 
 
 
Figure 1 
 
Magnetic resonance imaging (T1-weighted imaging) showed an irregularly-shaped mass with variable low intensity (white arrows) in the right parotid gland (A). The tumour was near atrophic salivary gland tissue (asterisk), and showed invasive growth and ... 
 
 
 
Macroscopically, an ill-defined greyish-white mass was observed in the anterior portion of the right parotid gland. Histologically, most of the tumour consisted of nest-like growth of atypical squamous epithelium with keratinization and, focally, cystic change, consistent with the usual type of moderately differentiated SCC around atrophic salivary glands. However, ∼20% of the tumour was composed of glandular structures and intracytoplasmic lumens, which were positive for mucin with Alcian blue and periodic acid–Schiff staining (Figure 1B–E); this was considered to be an adenocarcinomatous component. Both components were intermingled. The tumour stroma was desmoplastic, but no goblet intermediate cells were seen. Focal intraductal proliferations of atypical cells, which were considered to be in-situ lesions, were also observed in the relatively large excretory ducts (Figure 2). The residual tissues of the parotid gland showed marked atrophy. The tumour in this case consisted of three components: (i) moderately differentiated SCC; (ii) adenocarcinoma; and (iii) intraductal lesions. Immunocytochemistry for CK7 and p63 distinguished between the glandular and squamous components (see Supporting Information). As this tumour was present in the parotid gland on both MRI and histological examination, and in-situ lesions were seen in the large excretory ducts, we believe that this tumour was ASC arising from the parotid gland. 
 
 
 
Figure 2 
 
A focus of in-situ lesion, which consisted of intraductal proliferation of atypical cells (arrows), was observed in a relatively large excretory duct (H&E). 
 
 
 
Although rare, ASC of the head and neck region is most often seen in the tongue, oral floor, and larynx, with a peak in the fifth decade of life (male/female ratio, 3:1). Alos et al.3 suggested that the origin of ASC was the surface epithelium, although Gerughty et al.,4 in 1968, proposed that it was the excretory duct of seromucinous glands, indicating that ductal carcinoma in-situ (DCIS) was seen in four of 10 cases of ASC. Certainly, most ASCs of the head and neck region might arise from the surface epithelium, owing to the existence of neoplastic squamous epithelium (severe dysplasia or CIS), but we believe that our case might have arisen from the large excretory ducts of the parotid gland. 
 
A differential diagnosis should be considered, especially salivary gland mucoepidermoid carcinoma (MEC). High-grade MEC is usually composed predominantly of intermediate or epidermoid cells but without keratin formation. MEC often has a lobular pattern, and infiltrates by forming wide sheets of neoplastic cells with round contours, whereas ASC infiltrates as thin trabeculae or solid small nests in desmoplastic stroma, typical of SCC. Although ASC was previously considered to be the same entity as MEC,5,6 the tumours need to be differentiated from each other as they can have different outcomes: ASC is a very aggressive tumour, with a worse prognosis than high-grade MEC.7 Recently, we found that ASC of the head and neck region had a high rate of lymph node metastasis and a worse prognosis, especially in cases of MUC4 expression (K. Kusafuka et al., submitted). The most important histological features of ASC that differentiate it from MEC are: (i) keratin formation and intercellular bridges; (ii) desmoplasia; (iii) irregularly-shaped nests; (iv) prominent invasive growth near the tissues; and (v) the relative absence of goblet and intermediate cells. MECs, especially of low grade, frequently show CRTC1–MAML2 gene rearrangement, and even high-grade MECs infrequently show such a rearrangement.8 ASC often mimics high-grade MEC. 
 
To the best of our knowledge, this case may be the first well-documented case of ASC of a major salivary gland. It may be that some high-grade translocation-negative so-called MECs are in fact examples of ASC.

Sir: Adenosquamous carcinoma (ASC) is a rare malignant tumour in the head and neck region, and usually occurs as a mucosal carcinoma. The World Health Organization classification 1 categorizes this tumour as a variant of squamous cell carcinoma (SCC), whereas the Armed Forces Institute of Pathology (AFIP) classification 2 categorizes it as a salivary gland tumour. In the AFIP guidelines, the occurrence of ASC is limited to the minor salivary glands. Alos et al. 3 suggested the following criteria for the diagnosis of ASC: (i) the most common component is usually keratinizing SCC; (ii) the second component is adenocarcinoma in the deeper portion; and (iii) severe dysplasia or carcinoma in-situ (CIS) is seen in the surface epithelium. We report here a case of ASC arising from the parotid gland.
A 78-year-old Japanese woman developed rapid swelling in the right buccal region, and was admitted to our hospital 2 months later. Intraoral examination showed no mucosal lesions, but a 30 9 40-mm irregularly-shaped mass was seen in the anterior portion of the right parotid gland. Magnetic resonance imaging (MRI) showed that this mass had low intensity on T1-weighted imaging and partially high intensity on T2-weighted imaging ( Figure 1A). Positron emission tomography showed no evidence of other primary lesions. Total parotidectomy was performed following a clinical diagnosis of parotid gland carcinoma.
Macroscopically, an ill-defined greyish-white mass was observed in the anterior portion of the right parotid gland. Histologically, most of the tumour consisted of nest-like growth of atypical squamous epithelium with keratinization and, focally, cystic change, consistent with the usual type of moderately differentiated SCC around atrophic salivary glands. However, 20% of the tumour was composed of glandular structures and intracytoplasmic lumens, which were positive for mucin with Alcian blue and periodic acid-Schiff staining ( Figure 1B-E); this was considered to be an adenocarcinomatous component. Both components were intermingled. The tumour stroma was desmoplastic, but no goblet intermediate cells were seen. Focal intraductal proliferations of atypical cells, which were considered to be in-situ lesions, were also observed in the relatively large excretory ducts ( Figure 2). The residual tissues of the parotid gland showed marked atrophy. The tumour in this case consisted of three components: (i) moderately differentiated SCC; (ii) adenocarcinoma; and (iii) intraductal lesions. Immunocytochemistry for CK7 and p63 distinguished between the glandular and squamous components (see Supporting Information). As this tumour was present in the parotid gland on both MRI and histological examination, and in-situ lesions were seen in the large excretory ducts, we believe that this tumour was ASC arising from the parotid gland.
Although rare, ASC of the head and neck region is most often seen in the tongue, oral floor, and larynx, with a peak in the fifth decade of life (male/female ratio, 3:1). Alos et al. 3 suggested that the origin of ASC was the surface epithelium, although Gerughty et al., 4 in 1968, proposed that it was the excretory duct of seromucinous glands, indicating that ductal carcinoma in-situ (DCIS) was seen in four of 10 cases of ASC. Certainly, most ASCs of the head and neck region might arise from the surface epithelium, owing to the existence of neoplastic squamous epithelium (severe dysplasia or CIS), but we believe that our case might have arisen from the large excretory ducts of the parotid gland.
A differential diagnosis should be considered, especially salivary gland mucoepidermoid carcinoma (MEC). High-grade MEC is usually composed predominantly of intermediate or epidermoid cells but without keratin formation. MEC often has a lobular pattern, and infiltrates by forming wide sheets of neoplastic cells with round contours, whereas ASC infiltrates as thin trabeculae or solid small nests in desmoplastic stroma, typical of SCC. Although ASC was previously considered to be the same entity as MEC, 5,6 the tumours need to be differentiated from each other as they can have different outcomes: ASC is a very aggressive tumour, with a worse prognosis than highgrade MEC. 7 Recently, we found that ASC of the head and neck region had a high rate of lymph node metastasis and a worse prognosis, especially in cases of To the best of our knowledge, this case may be the first well-documented case of ASC of a major salivary gland. It may be that some high-grade translocation-negative so-called MECs are in fact examples of ASC.
The authors thank Isamu Hayashi, Yoichi Watanabe, Sachiyo Oono, Kaori Nagata, Hiroshi Tashiro, Koji Muramatsu, Masatake Honda, Masato Abe, Chiho Tashiro, Takuya Kawasaki, Masatsugu Abe, Shogo Fujii, Kyoko Tanaka, and Kazumi Yamamoto, and the staff of the Pathology Division, Shizuoka Cancer Centre, Shizuoka, Japan, for excellent technical assistance. Written informed consent was obtained from the patient for publication of this case report and the accompanying images.