Birt-Hogg-Dubé Syndrome: A Case Report Describing Sonographic Evaluation of Salivary Gland Oncocytomas

INTRODUCTION

Birt-Hogg-Dubé (BHD) is a rare autosomal dominant hereditary syndrome first described in 1977 that arises due to a mutation in the folliculin (FLCN) gene, a tumor suppressor gene located on chromosome 17p11.2.^[1] The condition has been reported in more than 400 families.^[2] Most patients with an FLCN mutation have benign skin hamartomas of the head and neck most commonly associated with the hair follicle and known as fibrofolliculomas. Additional findings include pulmonary cysts with an incidence of spontaneous pneumothoraces in 25% of patients.^[3] It is important to highlight that BHD is a hereditary renal cell carcinoma (RCC) syndrome and patients have a significantly increased risk of both benign and malignant renal lesions.^[2,4] Other less common findings of BHD include lipomas, parathyroid adenomas, salivary tumors, and colonic polyps/tumors. Early detection of BHD allows for focused treatment, leading to decreased morbidity and mortality. The most common salivary gland tumor reported in BHD is a salivary gland oncocytoma which can present as a palpable neck or facial mass. Ultrasound evaluation of the salivary glands is a fast, inexpensive modality which can accurately assess pathology without radiation exposure.^[3] The salivary glands on ultrasound are typically homogenous structures that are hyperechoic compared to adjacent muscles.^[5] Their evaluation can be challenging due to body habitus, complexity of the surrounding anatomic structures, and the extension of the parotid glands into the deep spaces of the neck. In this case, we will present the sonographic characteristics of salivary gland oncocytomas in a patient with BHD, differential considerations, and literature search.

CASE REPORT

A 51-year-old female with a history of the left-sided spontaneous pneumothoraces and bilateral kidney lesions [Figure 1] presented with enlarging palpable nodules in the right submandibular and left parotid regions. Gray scale, ultrasound, and color flow Doppler of the neck were performed which revealed a homogenous well-circumscribed hypoechoic lesion in the right submandibular gland measuring approximately 1.5 × 0.9 × 0.9 cm and an additional 1.5 × 1.3 × 1.1 cm lesion in the left parotid gland [Figure 2]. Both of these lesions demonstrated diffuse hypervascularity. The working differential diagnosis included salivary gland oncocytoma versus pleomorphic adenoma. Given the multiplicity and the patient’s medical history, most likely etiology was felt to be salivary gland oncocytomas in a patient with known history of BHD.

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Figure 1:

51 year old female with Birt-Hogg-Dube Syndrome. (a) Chest radiograph demonstrates a large left pneumothorax. (b) Grayscale longitudinal plane image demonstrates a 3.1 × 2.5 cm well circumscribed hyperechoic lesion in the upper pole of the right kidney suggestive of Angiomyolipoma (AML). (c) Axial contrast enhanced image demonstrates corresponding hypoattenuating lesion containing macroscopic fat compatible with AML.

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Figure 2:

51 year old female with Birt-Hogg-Dube Syndrome and Salivary Gland Oncocytomas. (a) Longitudinal Grayscale image demonstrated a 1.6 × 1.3 × 1.1 cm homogenous hypoechoic lesion in the left parotid gland. (b) Corresponding color Doppler image demonstrate diffuse hypervascularity. (c) Longitudinal Grayscale image of parotid gland demonstrates a 1.5 × 0.9 × 0.9 cm homogenous hypoechoic lesion in the right submandibular gland. (d) Corresponding real time color Doppler image demonstrate diffuse hypervascularity.

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DISCUSSION

There are multiple hereditary RCC syndromes including BHD, Von Hippel–Lindau (VHL), hereditary papillary RCC (HPRCC), hereditary leiomyomatosis and RCC (HLRCC), BAP1 mutant disease, and tuberous sclerosis complex that increase the risk of developing cancer, in particular, renal cell carcinoma.^[1,6,7] These syndromes are summarized in Table 1.

BHD is an autosomal dominant hereditary syndrome that arises due to a mutation in the FLCN tumor suppressor gene. BHD presents most commonly with epithelial hamartomas, pleural cysts, spontaneous pneumothoraces, and renal cell carcinoma.^[2,4] In BHD, the most common renal tumor is a hybrid chromophobe/oncocytic renal cancer.^[3] Chromophobe RCCs are derived from intercalated cells that reside in the renal collecting duct; patients with inactivating mutations in the FLCN gene are at risk of developing bilateral chromophobe RCCs with multiple foci.^[8] Early diagnosis of BHD is a key to ensure appropriate renal screening and early detection of RCC which significantly decreases mortality in these patients.

Sonographic evaluation of the salivary glands can be challenging due to their location; the parotid gland can be especially challenging due to its deep location often extending behind the acoustic shadow of the mandible. Our patient presented with enlarging palpable nodules in the right submandibular and left parotid regions. The multiple hypoechoic well-circumscribed lesions in our patient with a history of renal lesions and pneumothoraces are most compatible with salivary gland oncocytomas. Oncocytoma is the most common salivary gland solitary lesion in patients with BHD.^[1,2] Oncocytomas occur in multiple organs, for example, renal and thyroid oncocytomas, and are named for their characteristic cell type, the oncocyte.^[7,9] Oncocytes are epithelial cells with excess number of mitochondria that have a strong eosin stain.^[8,10] On ultrasound, oncocytomas are homogeneously hypoechoic, well-circumscribed, and differentiated tumors with increased vascularity. The differential diagnosis for solitary salivary gland lesions is summarized in Table 2 and includes pleomorphic adenoma, Warthin tumor, adenoid cystic carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, and metastasis.^{[6,8,11,12,13]}

Differentiating these lesions can be challenging. Malignant lesions can have more infiltrative poorly differentiated margins; however, less aggressive tumors can be well circumscribed and are difficult to differentiate from more benign lesions. Unlike an oncocytoma which is homogenous in echotexture, these malignant lesions tend to be more heterogeneous and can be partially cystic.^[14,15] It is important to consider the clinical history when evaluating salivary gland lesions.

CONCLUSION

Sonographic evaluation of salivary gland lesions is a fast and inexpensive method. This case report illustrates the imaging features of salivary gland tumors and the importance of clinical history in diagnosis. Oncocytomas are the most common lesion of the salivary gland in patients with BH; early detection can result in appropriate treatment and decrease mortality.^[16,17]