Role of Volumetric Modulated Arc Technique Radiotherapy in a Rare Case of Intraductal Apocrine Carcinoma of Parotid Gland

Abstract

Introduction

Apocrine carcinoma, a cancer of sweat glands, is very rare, with a global incidence of 0.0049 to 0.0173 cases per 100,000 persons annually. It is usually found in axilla and anogenital areas. The intraductal apocrine variety of salivary duct carcinoma in the parotid gland is very rare and aggressive and may be due to ectopic sweat glands in the parotid gland duct or metaplastic change of the salivary duct epithelium. It usually presents in an advanced stage. Even though surgery is the standard of care in most head and neck cancers, there are no standard guidelines for the treatment of intraductal apocrine parotid carcinoma, which is different from other head and neck cancers due to its rare incidence, aggressive behavior, and poor prognosis.

Case presentation

We present a rare case of intraductal apocrine salivary duct carcinoma of the left parotid gland, presented in a locally advanced stage with very high chances of recurrence after surgery, and discuss the role of volumetric modulated arc technique radiotherapy in its management.

Conclusion

Intraductal apocrine salivary duct carcinoma usually has androgen receptor expression, and lack of expression is associated poor prognosis. Even with complete resection, it has a high recurrence rate. Volumetric modulated arc technique radiotherapy (VMAT) decreases recurrence and increases survival by irradiating the areas more likely of recurrence, with minimal toxicity to surrounding normal tissues.

Introduction

Apocrine carcinoma is cancer of sweat glands. It is quite rare, with a global incidence of 0.0049 to 0.0173 cases per 100,000 persons per year. ¹ It is mostly found in apocrine-rich areas such as the axilla and anogenital areas; however, it can be found in any body part, including the scalp, chest, frontal region, spleen, hand, finger, and lip. ^1-6 The mean age at diagnosis is 62 years, and it is twice as common in men as women. ⁷ Carcinomas with apocrine differentiation not related to extramammary Paget’s disease, ductal breast carcinoma, Moll’s glands adenocarcinoma, or ceruminous glands carcinoma are very uncommon. ⁸ Apocrine carcinoma in the parotid gland duct can be explained either by the presence of ectopic sweat glands in the parotid gland duct or metaplastic change of the salivary gland epithelium into an apocrine-like secretory epithelium. ⁹ Overall, salivary gland carcinomas are rare with an incidence of 1.3 per 100,000 people. ¹⁰ Salivary duct carcinoma (SDC), an aggressive malignancy of the salivary glands, is even more rare. Apocrine-type SDC is so rare that it was not presented as a separate entity in the World Health Organization’s 2017 classification of salivary gland tumors. ¹¹ We present a rare case of intraductal apocrine SDC of the left parotid gland, which presented in a locally advanced stage, along with its treatment with surgery, chemotherapy, and radiation by volumetric modulated arc technique (VMAT).

Case Report

A 59-year-old man had a rapidly progressing mass with mild pain in the left periauricular area since September 2020. However, his mouth opening was adequate. His comorbidities included hypertension, and he was allergic to the sulphonamide group of drugs. He first visited the hospital in December 2020, where magnetic resonance imaging (MRI) was done. It showed a left parotid mass of 3.6 × 3 × 3.6 cm, involving both superficial and deep lobes with enlarged left-level Ib-III cervical lymph nodes. Positron emission tomography–computed tomography (PET-CT) scan showed fluorodeoxyglucose avid (standardized uptake value, max 15.1); lobulated soft tissue mass of 3.4 × 3.7 × 4.1 cm in the left parotid gland involving superficial and deep lobes and abutting skin; and few enlarged lymph nodes in the left periauricular, infra-parotid (17.5 mm short axis diameter, standard uptake value max 12.8), and left cervical level II (16 mm short axis diameter, standard uptake value max 17.8) (Figure 1A). In January 2021, the patient underwent left radical parotidectomy with left modified neck dissection and left facial nerve reconstruction with right sural nerve cable grafting.

Figure 1:

(A) PET-CT scan showing fluorodeoxyglucose, avid, lobulated soft tissue mass in left parotid gland involving superficial and deep lobes. (B) Contouring tumor bed as clinical target volume (red), elective nodal volume as clinical target volume (orange), and left cervical level II with extranodal extension as clinical target volume (green); and giving 5 mm planning target volume (blue and cyan) over all clinical target volumes. (C) Color wash showing 95% coverage of planning target volume by prescribed dose. (D) Dose volume histogram showing organs at risk and planning target volume coverage (details in Table 1).

Histopathology showed apocrine-type intraductal SDC of the left parotid gland. The tumor was 3.2 × 3 ×2 .7 cm, with evidence of apocrine snouting, multiple foci of comedo necrosis, and the presence of lymphatic and perineural invasion. The margins were close. Two lymph nodes in level II were positive for metastasis with extranodal extension. As a result, it was staged as pT2N3bM0. On immunohistochemistry, invasive as well as intraductal components were positive for androgen receptor (AR) and cytokeratin 7(CK7), although negative for S100, p40, and CK5/6 highlighted intact abluminal cell layer, Her2neu equivocal. On fluoroscence in situ hybridization, there was monosomy of chromosome 17, Her2neu not amplified.

The patient presented in our hospital in February 2021 (Table 2). Radiological examination showed no residual disease. In view of his locally advanced carcinoma and extranodal extension in left cervical lymph nodes, he was subjected to adjuvant chemoradiation. The patient received radiotherapy in February and March 2021 to a dose of 66 Gy/33 fractions in 2 phases with VMAT radiotherapy, which ensures the least toxicity to surrounding critical structures like the right parotid gland, cochlea, brainstem, spinal cord, mandible, larynx, and esophagus, also called the organs at risk (Figure 1B-D). Doses to organs at risk were within limits (Table 1). Concurrent weekly chemotherapy was given with an injection of cisplatin at 40 mg/m², starting on day one of radiation. The patient tolerated the treatment well with Common Terminology Criteria for Adverse Events (CTCAE v. 4.0), ¹² including grade 1 fatigue, grade 1 dermatitis, grade 2 mucositis, and grade 2 dysphagia, with no hematological toxicity. The first follow-up MRI for the face and neck after 3 months revealed no evidence of disease. The patient was put on follow-up because 9 months passed with no complaints.

Table 2:

Timeline of patient’s clinical course

Date	Summary	Tests/intervention
September 2020	Intitiation of swelling in left periauricular area
December 2020	First visit to hospital	MRI, y (PET-CT)
January 2021		Left radical parotidectomy with left modified radical neck dissection
February 2021	Radiological examinations done including MRI face and neck	No residual disease
February-March 2021		Received VMAT radiotherapy to 66 Gy/33 Fr
June 2021	MRI face and neck	No evidence of disease
October 2021	MRI face and neck	No evidence of disease
December 2021	Clinical examination	No evidence of disease

AR , androgen receptor; CT , computed tomography; MRI , magnetic resonance imaging; PET-CT , positron emission tomography; SDC , salivary duct carcinoma; VMAT , volumated modulated arc technique.

Table 1:

Organs at risk, contoured with dose constraints to be achieved as per literature and doses achieved

Organs at risk	Dose constraint	Dose achieved
Brainstem	Max < 54 Gy (RTOG 0225)	38.51 Gy
Cochlea, left	Mean < 45 Gy (QUANTEC)	31.9 Gy
Cochlea, right	Mean < 45 Gy (QUANTEC)	15.5 Gy
Spinal cord	Max < 45 Gy (RTOG 0623)	53.8 Gy
PRV cord	Max < 50 Gy (RTOG 0623)	42.8 Gy
Right parotid	Mean < 26 Gy (RTOG 0912)	22.2 Gy
Mandible	Max < 70 Gy	68.4 Gy
Esophagus	Mean < 45 Gy (RTOG 0920)	25.1 Gy
Larynx	Mean < 45 Gy (RTOG 0920)	36.52 Gy

OARs, organs at risk; PRV, Planning organ at risk volume; RTOG, radiation therapy oncology group.

Discussion

Salivary duct carcinoma is a prototypic aggressive form of salivary gland carcinoma. Usually such patients present with locally advanced disease like large tumor and extraglandular extension. ^13,14 SDC is the most common carcinoma arising from pleomorphic adenoma. ^15,16 SDC is usually classified as micropapillary, sarcomatoid, and mucinous variants. ¹⁷ AR expression correlates with the apocrine phenotype, and the lack of AR expression is associated poor prognosis. ^14,18 Factors associated with poor prognosis are perineural invasion, vascular invasion, extranodal extension, higher N-stage, and facial nerve involvement. Men have substantially worse disease-free survival; and advanced age and nodal stage (≥ N2) have worse overall survival. ¹⁹

Surgery is the main treatment. Radiotherapy and chemotherapy are decided based on the surgical outcome or if the tumor is not resectable. A retrospective study by Kaura et al ²⁰ suggested carrying out prophylactic neck dissection in patients with SDC due to the high rate of occult lymph node metastasis in these patients. However, a study by Pan et al ²¹ showed that sentinel lymph node biopsy was also an option for management of the neck in parotid malignancies. Due to the rarity and histological heterogeneity of parotid malignancies, the formulation of a randomized controlled trial to define their management is not feasible. ¹⁰ As a result, data on radiotherapy contouring and planning guidelines are limited. A systematic review by Ng-Chen-Hin et al ²² suggested that elective nodal irradiation in patients with post-operated tumors showing high grade, lymphovascular invasion or T3/T4 disease yield a better 5-year locoregional control rate of 74% to 100%. VMAT radiotherapy is an advanced technique of radiotherapy where the radiation dose is delivered continuously as the machine rotates like an arc. It accurately shapes and changes the intensity of the radiation dose as per the tumor while minimizing the dose to surrounding organs.

Conclusion

Apocrine carcinomas are very rare, and location outside the breast and axilla are even more rare. Salivary duct carcinomas are very rare and aggressive. Therefore, there are no standard guidelines specific for intraductal apocrine SDC of the parotid gland. This disease has a poor prognosis and high chances of recurrence, even after complete resection. More case reports are required to establish standards of care, including proper radiotherapy guidelines and effective chemotherapy agents.