Abstract

Background: Adenoid cystic carcinoma (ACC) is an uncommon tumor with nonspecific clinicoradiological features thereby masquerading other nonneoplastic and neoplastic entities. Materials and Methods: Cases of ACC were retrospectively reviewed over a period of 4 years. The clinical details of these patients including fine-needle aspiration cytology (FNAC) and imaging findings were retrieved. Diagnosis was confirmed on histomorphology and supplemented with immunohistochemistry (IHC). Results:: Thirty cases of ACC were included in the study. Mean patient age was 55.5 years with a slight female preponderance. Among the 30 ACCs, 10 (33.4%) were located in submandibular gland, 7 (23.4%) in parotid gland, 6 (20%) in sublingual gland, 2 (6.7%) in lung and one each (3.33%) in nasal cavity, breast, cervix, lip, and skin of face. Preoperative imaging was suggestive of malignancy in 29 cases while a single case of parotid gland ACC was misdiagnosed as benign salivary gland neoplasm. FNAC was performed in 29 cases with a diagnostic accuracy of 82.7%. Histopathological examination showed characteristic features of ACC in all cases with perineural invasion seen in 7 cases. On IHC, positivity for cytokeratin was seen in all cases, cluster of differentiation 117 in 24 cases, thyroid transcription factor-1 in two cases and human epidermal growth factor receptor/neu in two cases. All cases were negative for estrogen receptor and progesterone receptor IHC. Mean Ki-67 score was 47.8%. Conclusion: ACCs are notorious tumors showing slow growth kinetics with propensity for perineural invasion, late recurrences, and distant metastasis. It should be kept in mind as a differential diagnosis at unusual sites other than salivary glands.

Introduction

Adenoid cystic carcinoma (ACC) is a relatively uncommon tumor, with a reported incidence of 4.5 cases per million individuals.[1] It most commonly involves the salivary glands.[2] Involvement of lacrimal gland, breasts, uterine cervix, esophagus, lungs, and prostate is exceedingly rare and infrequently reported.[3]

Owing to nonspecific clinicoradiological features, these tumors masquerade other nonneoplastic and neoplastic entities. On literature search scattered case reports and case series of site specific ACCs were found without any large study on the incidence, distribution and clinicopathological features of ACC at different sites. Keeping in view these considerations, we retrospectively analyzed cases of ACCs over a period of 4 years in a tertiary care setting. Our study highlights the clinicopathological features of ACC with special emphasis on the utility of preoperative diagnostic modalities such as imaging and fine-needle aspiration cytology (FNAC).

Materials and Methods

The archives of Department of Histopathology were retrospectively reviewed from January 2012 to January 2016. Of the 57,890 cases received, cases of ACC were included in the study. The medical records and clinical details of these patients including preoperative FNAC and/or radiological findings on computed tomography (CT)/magnetic resonance imaging (MRI)/mammography were retrieved. FNAC was performed wherever possible. Repeat aspiration was performed if the first FNA attempt yielded inadequate material or was inconclusive for diagnosis. Smears were then air dried and stained with May-Grünwald Giemsa stain. All the patients underwent curative surgery. The excised specimen was fixed in 10% neutral buffered formalin and sent for histopathological examination. Diagnosis was confirmed on hematoxylin and eosin (H and E) stained, formalin-fixed paraffin embedded sections. These tumors were graded as per recommendations by Szanto et al.[4] Tumors containing only tubular or cribriform growth pattern were categorized as Grade I tumors, tumors containing cribriform or tubular growth with <30>30% solid component as Grade III tumors. A detailed immunohistochemical (IHC) panel consisting of cytokeratin (CK) (Biocare Medical, Clone: AE1/AE3), cluster of differentiation 117 (CD117) 117 (Biocare Medical, Clone: EP10), thyroid transcription factor-1 (TTF-1) (Biocare Medical, Clone: 8G7G3/1), estrogen receptor (ER) (Thermo Scientific, Clone: SP1), progesterone receptor (PR) (Thermo Scientific, Clone: SP2), human epidermal growth factor receptor (HER2/neu) (BioGenex, Clone EP1045Y), and Ki-67 (Thermo Scientific, Clone: SP6) was applied to all cases. In brief, sections measuring 3–4 μm thick were cut, deparaffinized with xylene and brought to water through graded levels of alcohol. Endogenous peroxidase activity was blocked by treating the slides with hydrogen peroxide for 30 min at room temperature. Antigen retrieval was done by immersing the slides in citrate buffer using the pressure cooker method. Then, the slides were incubated overnight with the primary antibody (rabbit polyclonal) at 4°C in a humidified chamber. The following day secondary antibody was added. The sections were then incubated with di amino benzidine for visualization of the peroxidase reaction. After being washed in water, the sections were counter stained with hematoxylin, dehydrated in alcohol, cleared in xylene, and mounted. IHC was interpreted in a binary fashion as positive or negative. Ki-67 index was calculated by counting the total number of Ki-67 positive cells in 100 consecutive tumor cells.

The FNAC smears, H and E stained sections, and IHC slides of all the cases were reviewed by two pathologists and correlated with the clinical findings including radiology.

Results

Out of 57,890 cases received in the department over a period of 4 years, we found only 30 cases of ACC [Table 1]. The mean patient age at the time of surgery was 55.5 years (range 19–64 years). There were 13 male and 17 female patients with a male:female ratio of 1:1.3. Among these 30 tumors, 10 (33.4%) were located in the submandibular gland, 7 (23.4%) in the parotid gland, 6 (20%) in the sublingual gland, 2 (6.7%) in the lung and one each (3.33%) in nasal cavity, breast, cervix, lip, and skin of face.

| Figure.1:Contrast enhanced computed tomography image shows (a) Heterogeneously enhancing mass lesion involving superficial and deep lobes of right parotid gland, (b) Small lobulated mass lesion just anterior to the left submandibular gland with areas of necrosis, (c) Heterogeneously enhancing mass in posterior segment of right upper lobe, (d) Homogeneous mass involving the nasal septum along with bony erosion of medial wall of right orbit, (e) Heterogeneously enhancing cervical mass seen obstructing the endocervical canal, (f) Breast mammography image shows a spiculated mass in upper outer quadrant of left breast suggestive of BIRADS IV

FNAC was performed in all cases except for the mass in uterine cervix due to inaccessibility of lesion. Further, CT-guided FNAC was performed for the lung lesions. FNA smears were moderately cellular with cells arranged in variably sized cohesive clusters and occasional cup shaped fragments [Figure 2]a. The individual tumor cells were small with scant basophilic cytoplasm and central round hyperchromatic nucleus. Numerous variable sized, spherical, and pink hyaline globules were seen both within and outside the cell clusters [Figure 2]b. Accurate diagnosis of ACC was made in 82.7

| Figure.1:Contrast enhanced computed tomography image shows (a) Heterogeneously enhancing mass lesion involving superficial and deep lobes of right parotid gland, (b) Small lobulated mass lesion just anterior to the left submandibular gland with areas of necrosis, (c) Heterogeneously enhancing mass in posterior segment of right upper lobe, (d) Homogeneous mass involving the nasal septum along with bony erosion of medial wall of right orbit, (e) Heterogeneously enhancing cervical mass seen obstructing the endocervical canal, (f) Breast mammography image shows a spiculated mass in upper outer quadrant of left breast suggestive of BIRADS IV

| Figure.2Photomicrograph of May Grünwald Giemsa stained fine needle aspiration smears show; (a) Moderate cellularity with small basaloid cells arranged in cohesive clusters and occasional cup shaped fragments (inset) (×200). (b) Tumor cells are embedded within spherical, pink hyaline globules (inset) (×200). Photomicrograph of H and E stained sections show; (c) Cribriform arrangement of tumor cells forming pseudocysts filled with basement membrane like basophilic material (×100). (d) Tubular arrangement of cells which are round to cuboidal with scant eosinophilic cytoplasm and central hyperchromatic nucleus (×400)

| Figure.3On immunohistochemistry tumor cells were positive for; (a) cytokeratin (immunostain, ×200), (b) cluster of differentiation 117 (immunostain, ×200), (c) thyroid transcription factor-1 (immunostain, ×200), (d) Ki-67 (immunostain, ×200)

References