Case 1 -

Basal Cell Adenocarcinoma Gregg Allen Staerkel M.D. Anderson Cancer Center Houston, TX

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Clinical History A 44-year-old woman presented with a left parotid gland mass. It was first noted by the patient one month prior to her seeking a medical opinion. The patient stated that she had progressive left-sided otalgia, but no otorrhea, hearing loss, dysphagia, odynophagia, trismus, fever, chills or night sweats. The patient's past medical, family and social histories were significant for a brief period of cigarette smoking (quitting 15 years ago), a father and maternal uncle with lung cancer and two additional relatives (maternal aunt and paternal uncle) with cancer, but of unknown etiology. On palpation, the left postauricular area disclosed a tender mass that was firm, hypomobile, with ill-defined margins. A CT scan of the head and neck showed a 3.5 x 2.8 x 2.5 cm mass arising in the tail of the parotid gland extending medially to the mastoid and possibly to the region of the stylomastoid foramen. A fine needle aspiration was performed. Representative areas are illustrated. Case 1 - Figure 1 - Smear shows a moderately cellular aspirate with largely cohesive, basaloid cell groups. Nuclei are round to oval with evenly dispersed chromatin and hyperchromasia. The lower right side of the cell group illustrated shows intercellular hyaline-like material that is both globular and linear in nature. Mitotic activity and necrosis are not identified. (Diff-Quik, medium power) Case 1 - Figure 2 - Two distinct cell group patterns are seen: tubular and solid sheet. Nuclei seen within the tubular fragment are much tighter packed and more basaloid in appearance than most cells seen within the fragment displaying a solid growth. (Papanicolaou, low power) Case 1 - Figure 3 - Focally, squamoid appearing cells are seen. These cells are identified by their larger, paler elongated nuclei and greater amounts of cytoplasm, as measured by the separation between nuclei. (Papanicolaou, medium power) Case 1 - Figure 4 - This basaloid cell fragment shows a slight tendency for nuclei to palisade, particularly at the cell group's edge. (Papanicolaou, medium power) Case 1 - Figure 5 - Focal areas of abundant hyaline-like material are seen in a vaguely globular pattern, which is delineated by small, round, basaloid cells. (Papanicolaou, low power) Cytologic Diagnosis: Basal cell neoplasm, favoring basal cell adenocarcinoma Histologic Diagnosis: Basal cell adenocarcinoma Case 1 - Figure 6 - Histologic section showing small and large nests of basaloid cells. Centrally some cells are larger and pale with a little more visible cytoplasm. These cells blend with the surrounding more basaloid cells. A degree of nuclear pallisading is seen at the edges of some of the basaloid cell nests. (H & E, low power) Case 1 - Figure 7 - Tumor cells are seen adjacent to nerve branches. In addition, a small focus of squamoid differentiation is present. (H & E, low power) Cytologic Diagnosis Basal cell neoplasm, favoring basal cell adenocarcinoma Histologic Diagnosis Basal cell adenocarcinoma Cytologic Findings Four needle aspirations were performed after anesthetic was administered due to the discomfort the patient felt on both palpation and aspiration. All aspirations yielded moderately abundant cellularity, which consisted largely of cohesive, basaloid cell groups. Cell groups were arranged in both tubular and solid sheet patterns. All groups were three-dimensional in nature. These groups displayed minimal cytoplasm and nuclei that were round to oval with evenly dispersed chromatin, hyperchromasia and smooth nuclear contours. Focally, at the periphery of a few cell groups nuclear pallisading was seen. Also present focally was abundant hyalin-like material that, in areas, showed a vaguely globular pattern surrounded by small, round, basaloid cells. Occasional cell fragments showed a more squamoid appearance. This was evident by the presence of more visible cytoplasm, displacing nuclei further apart within cell groups, and focal areas of elongated, spindled nuclei that layered upon each other. At the time of aspiration, the identification of basaloid and squamoid cell groups, focal palisades of nuclei and hyalin-like material within a tender mass arising in the area of the parotid gland was felt to be consistent with a salivary gland neoplasm. Primary consideration was for basal cell neoplasm (i.e., basal cell adenoma vs. basal cell adenocarcinoma) vs. adenoid cystic carcinoma. Since the initial two aspirates were significantly cellular, two additional aspirates were made for cell block preparation and subsequent histologic review. A review of the cell block preparation showed similar changes to those seen on cytologic smears with the exception of a rare mitotic figure. A diagnosis of basal cell neoplasm, favoring basal cell adenocarcinoma was made. Histologic and Clinical Follow-up A preoperative MRI scan showed a partially irregular, homogenous enhancing mass arising from the deep lobe of the left parotid gland and extending below the left ear and behind the bulk of the left parotid gland. When compared to the patient's outside CT study of a month ago, the mass had shown an increase in size (3.9 x 3.5 x 2.9 cm). There was no evidence of regional lymphadenopathy. The patient was taken to surgery where a left radical parotidectomy with sacrifice of the facial nerve, left lateral temporal bone resection, partial auriculectomy and left modified radical neck dissection was performed. These procedures were immediately followed by a facial nerve reconstruction, using a branch of the femoral cutaneous nerve of the left thigh, a soft tissue defect reconstruction using a vastus lateralis muscle free flap, harvested from the left thigh and a full thickness skin graft, taken from the neck. On cut section, the resected tumor was homogenously, tan-white, firm and solid with focally infiltrative margins. Histologic sections showed numerous nests of basaloid epithelial cells within a fibrous stroma. These cells infiltrated parotid gland parenchyma, adjacent connective tissue and the periphery of nerve bundles. While cells arranged in large and small nests predominated, a focal trabecular pattern was present. At the periphery of some cell groups, basaloid cells were seen in palisades. The center of larger cell nests showed slightly larger, paler nuclei with more apparent cytoplasm. These areas, plus layered areas of elongated nuclei, provided a slight squamoid appearance that blended inperceptively into adjacent basaloid cells. Within nests of cells, globules and irregular cylinders of eosinophilic hyalin-like material were seen, as were occasional mitotic figures. A diagnosis of basal cell adenocarcinoma, solid type, was rendered. Discussion: Basal cell adenocarcinomas comprise 1.6% of all salivary gland neoplasms and 2.9% of all malignant neoplasms of salivary gland origin. Most (nearly 90%) occur in the parotid gland with the patient's average age at diagnosis being 60 (range 27-92 years) with no gender predilection. Basal cell adenocarcinoma is the malignant counterpart to basal cell adenoma. Although most are thought to arise de novo, some are believed to arise in pre-existing basal cell adenomas. Basal cell adenocarcinoma is a low-grade malignant neoplasm with around 10% of cases metastasizing to lymph nodes or lung and one-third of cases showing local recurrence. Progressive swelling of the salivary gland, over weeks to years, is the consistent sign or symptom experienced by patients. However, some patients will note pain/tenderness and/or a rapid growth in size. In general, basal cell adenocarcinoma cannot be distinguished from basal cell adenoma by the review of cytologic features alone. Consequently, any differential diagnosis including one of these entities must include the other. Rarely, some cases will show nuclear atypia, mitotic figures and/or necrosis, which suggest malignancy. In addition, as in this case, a malignant nature is suspected when the mass on physical examination has an apparent irregular margin and marked tenderness is noted. These findings are consistent with tumor infiltration and possible neural involvement. Other entities to be added to the differential diagnosis are adenoid cystic carcinoma, basal cell/basaloid squamous cell carcinoma (metastatic from skin, lung, etc.) and pleomorphic adenoma. After basal cell adenoma, adenoid cystic carcinoma causes the greatest difficulty in diagnosis. The distinction of adenoid cystic carcinoma is important due to its long-term poorer prognosis. Key features favoring adenoid cystic carcinoma over basal cell carcinoma are as follows: 1) a more uniform population of basaloid cells (lacking the larger, paler nuclei with slightly greater cytoplasm); 2) presence of oval to angular nuclei (as apposed to round to oval); 3) presence of variably sized, but often large (relative to basal cell adenocarcinoma) acellular globules of hyalin matrix; 4) hyalin matrix which is more sharply delineated and completely surrounded by cells (as with basal cell adenocarcinoma, this matrix is cyanophilic to transparent on the Papanicolaou stain and metachromatic on Romanowsky stain; it should be remembered that the solid variant of adenoid cystic carcinoma may lack this hyalin matrix). Basal cell carcinoma and basaloid squamous cell carcinoma, presenting as a metastasis to the salivary gland, can cause confusion with basal cell adenocarcinoma because of the similarity of cells with basaloid features and the presence of nuclear palisades. Distinguishing features to observe in basal cell/basaloid squamous cell carcinomas are as follows: 1) prior or concurrent clinical/radiologic findings of epidermal sun damage and skin lesions or abnormality/mass of the upper aerodigestive tract (i.e., hypopharynx, base of tongue or supraglottic larynx); presentations consistent with basal cell carcinoma and basaloid squamous cell carcinoma, respectively; 2) absent or scant amounts of intercellular cyanophilic or metachromatic matrix (more fibrillar in nature when present); 3) greater frequency for nuclear atypia, mitotic activity and/or necrosis; 4) presence of keratin pearl formation (rare). Pleomorphic adenoma can be eliminated from the differential diagnosis, without much difficulty, unless matrix material is lacking. Features of pleomorphic adenoma, not found in basal cell adenocarcinoma include: 1) cohesive cell groupings displaying a more honeycomb-like pattern, as apposed to a haphazard cell arrangement; 2) presence of variable cell types, including plasmacytoid and spindled myoepithelial cells and cuboidal cells with more recognizable cytoplasm; 3) fine chromatin and an absence of hyperchromasia; 4) fibrillar chondromyxoid matrix with cells, not just peripheral, but embedded into the matrix. Ancillary studies are of little utility in cytologic preparations from these salivary gland lesions. But, if a decent cell block is made, the immunoperoxidase staining for smooth muscle actin, in basal cell adenoma and adenocarcinoma, is typically most evident in the basaloid cells located along the stromal interface of cell groups (i.e., periphery of cell nests). References Eillis GL, Auclair PL. Tumors of the salivary glands. Atlas of Tumor Pathology, 3rd series, fascicle 17. Washington, D.C.: Armed Forces Institute of Pathology, 1996: 81-94, 203-216, 257-267. Atula T, Klemi PJ, Donath K, et al. Basal cell adenocarcinoma of the parotid gland: a case report and review of the literature. J Laryngol Otol 107:862-864, 1993. Batsakis JG, Luna MA. Basaloid salivary carcinoma. Ann Otol Rhinol Laryngol 785-787, 1991. Pisharodi LR. Basal cell adenocarcinoma of the salivary gland: diagnosis by fine-needle aspiration cytology. Am J Clin Pathol 103:603-608, 1995. Stanley MW, Horwitz CA, Rollins SD, et al. Basal cell (monomorphic) and minimally pleomorphic adenomas of the salivary glands: distinction from the solid (anaplastic) type of adenoid cystic carcinoma in fine-needle aspiration. Am J Clin Pathol 106:35-41, 1996. Hood IC, Qizilbash AH, Salama SSS, Alexopoulou I. Basal-cell adenoma of parotid: difficulty of differentiation from adenoid cystic carcinoma on aspiration biopsy. Acta Cytol 27:515-520, 1983. Lee SS, Cho KJ, Jang JJ, Ham EK. Differential diagnosis of adenoid cystic carcinoma from pleomorphic adenoma of the salivary gland on fine needle aspiration cytology. Acta Cytol 40:1246-1252, 1996. Eisheikh TM, Bernacki EG. Fine needle aspiration cytology of cellular pleomorphic adenoma. Acta Cytol 40:1165-1175, 1996. Stanley MW, Horwitz CA, Bordales RH, et al. Basal cell carcinoma metastatic to the salivary glands: differential diagnosis in fine-needle aspiration cytology. Diagn Cytopathol 16:247-252, 1997.