An Unusual Presentation and Aggressive Course of Metastatic Myoepithelial Carcinoma

| September 1, 2019

by Nathalie C. Zeitouni, MDCM, FRCPC; Dih-Dih Huang, MD; and David Row, MD, FACS, FASCRS

Dr. Zeitouni is with the Department of Dermatology at University of Arizona COM, Phoenix and Mohs and Reconstructive Surgery at Medical Dermatology Specialists, Phoenix, Arizona. Drs. Huang and Row are with the Department of Surgery at Creighton University School of Medicine/St. Joseph’s Hospital and Medical Center in Phoenix, Arizona.

FUNDING: No funding was provided for this study.

DISCLOSURES: The authors have no conflicts of interest relevant to the content of this article.

Myoepithelial carcinomas are rare tumors that make up 1 to 2 percent of all salivary gland neoplasms. We present a case of a 55-year-old man with myoepithelial carcinoma that developed into widespread cutaneous, lung, and brain metastases refractory to treatment, including newer immunotherapies. Newer strategies or treatments are needed for the future benefit of patients with advanced disease. 

KEYWORDS: Cutaneous metastasis, myoepithelial carcinoma, scalp

 J Clin Aesthet Dermatol. 2019;12(9):46–48


Myoepithelial carcinomas are rare tumors that account for 1 to 2 percent of all salivary gland neoplasms.1–3 Head and neck myoepithelial carcinomas have variable behavior, but local recurrences and the development of metastases can be seen several months to years following the initial diagnosis.1 Cutaneous metastatic disease is, however, considered exceedingly rare.2 We present the unusual case of a 55-year-old man with myoepithelial carcinoma who developed widespread cutaneous, lung, and brain metastases that were refractory to treatment. 

Case Report

A 55-year-old man with a long and complex oncologic history presented to our clinic with several scalp lesions. At 11 years of age, he was diagnosed with rhabdomyosarcoma of the pharynx. He underwent surgery, radiation, and chemotherapy, achieving a complete response. Later, at age 44, he was diagnosed with invasive squamous cell carcinoma (SCC) of the posterior left and right pharynx, hypopharynx, and cervical esophagus, which was treated with a total laryngectomy and bilateral neck dissection due to his prior head and neck radiation. At age 45, he developed parotid swelling and underwent fine-needle aspiration, which demonstrated rare, highly atypical epithelial cells suspicious for carcinoma. However, low diagnostic cellularity precluded a definitive diagnosis at that time, and he was treated for a presumed recurrence of SCC with cetuximab and cyber knife radiosurgery at a previous institute. 

At age 54, he developed new scalp lesions (Figure 1) that were diagnosed initially as malignant chondroid syringoma by an outside pathology laboratory. Repeat excisional biopsies ultimately revealed metastatic myoepithelial carcinoma (Figures 2A and 2B). The neoplastic cells were immunoreactive for CAM 5.2 but negative for CK7, CK20, TTF-1, CDX-2, and brachyury. Positron emission tomography (PET-computed tomography (CT) scan showed evidence of necrosis posterior to the right parotid gland with bilateral pulmonary nodules that were presumed metastatic disease. 

Given his bilateral pulmonary metastases, the patient was initiated on nivolumab (3mg/kg every 2 weeks) with an anticipated course of 20 cycles. Chest CT imaging prior to Cycle 13 revealed stability in the majority of the pulmonary lesions, with a few appearing new or increased in size. A notation was made that it was unclear as to whether this represented an actual change versus differences in technique. The patient went on to receive an additional four cycles of nivolumab. Repeat imaging revealed progression of the disease in the chest, and immunotherapy was discontinued. While on nivolumab, the patient developed a new right occipital mass that required craniotomy for resection. Final pathology revealed metastatic myoepithelial carcinoma. Follow-up brain imaging revealed additional foci, and the patient went on to receive gamma knife stereotactic radiosurgery. Given the patient’s extensive oncologic history and disease course, he also underwent genetic testing (Invitae Corporation, San Francisco, California), which revealed that there were no pathogenic sequence variants or deletions/duplications identified. 

Concurrent with the cessation of nivolumab, the patient noted his scalp lesions were increasing in size. In addition, upon surveillance imaging of the brain, multiple intracranial metastases were observed, and he underwent two additional gamma knife stereotactic radiosurgery treatments. During that time, he started developing more cutaneous scalp and trunk lesions (Figure 3) and painful perineal and perianal masses. The symptomatic lesions were excised for palliative purposes in multiple sites (i.e., scalp, eyelid, perianal, perineum, extremities) as his disease progressed. Histologically, all lesions revealed metastatic myoepithelial carcinoma. The patient was initiated on cytotoxic chemotherapy to control the ongoing development and progression of new and current metastatic lesions, but stopped after two cycles of doxorubicin due to infectious complications and per his wishes. Over a subsequent two-month period, talimogene laherparepvec (TVEC) intralesional injections were administered to several cutaneous metastatic lesions on his trunk with no response.

 

Two weeks after his last TVEC treatment, the patient was admitted for acute kidney injury, hypercalcemia, hyperuricemia, hyperphosphatemia, and sepsis due to wound infection related to his palliative excisions. After stabilization in the hospital, the patient elected to go home with hospice and succumbed to his disease six weeks after his last treatment.

Discussion

Myoepithelial carcinoma of the head and neck is extremely rare. The tumor most frequently develops from the salivary glands—in particular, the parotid gland—in middle-aged patients.1–3 Although very rare, pediatric cases as young as two years of age have been reported.4 Histologically, the tumor shows morphological heterogeneity and stains positive for vimentin, S 100 protein, cytokeratin, and alpha smooth muscle actin.1–3 Molecular studies have revealed an EWSRI gene translocation in 45 percent of myoepithelial tumors.5 Interestingly, this gene translocation has also been reported in rhabdomyosarcomas, which our patient developed during childhood. Surgical resection of the tumor is the treatment of choice, while postoperative radiation therapy is recommended for high-risk lesions.1 Local recurrences following surgery are seen in 30 to 40 percent of patients, with a risk of 30 to 35 percent for metastasis, most commonly to the lungs and then the brain.1–3,6 The five-year survival rate was 31.8 percent in one series of 23 cases.1 

Cutaneous metastases of myoepithelial carcinoma are extremely rare and considered a possible indication of widespread disease with a poor prognosis.2 Interestingly, in a review of patients with cutaneous metastases, the diagnosis of their primary tumors was not reported initially as myoepithelial carcinoma.2 The long differential diagnosis list includes pleomorphic adenoma, myxoid chondrosarcoma, chondroid syringoma, parachordoma, myxoid liposarcoma, ossifying fibromyxoid tumour, synovial sarcoma, and epithelioid sarcoma.2 Our patient was initially diagnosed nine years prior with possible recurrent SCC, then with malignant chondroid syringoma based on the scalp nodules, and finally with metastatic myoepithelial carcinoma. Scalp tumors seen in our patient at presentation probably represented early local dissemination prior to his aggressive course.

Currently, there is no standard therapy for metastatic myoepithelial carcinoma. Surgical resection of metastases, radiotherapy, and chemotherapy with dacarbazine have been reported in the literature.1 Our patient underwent multiple palliative metastatectomies, as well as systemic immunotherapy with nivolumab, short-course doxorubicin, gamma knife stereotactic radiosurgery, and whole-brain radiation therapy. Nivolumab is a human IGGy antiprogrammed cell death-1 monoclonal antibody that works as a checkpoint inhibitor. It is approved by the United States Food and Drug Administration (FDA) for primary or metastatic urothelial carcinoma and is also used in the treatment of advanced melanoma, lung cancer, and renal cell carcinoma. TVEC, an FDA-approved viral oncolytic therapy for advanced and metastatic melanoma, was used in our patient on a compassionate basis in an attempt to control the local disease and as a possible adjunct to systemic chemotherapy. While his overall management might have palliated some of his symptoms, his disease continued to progress despite therapy. 

In conclusion, the diagnosis of cutaneous metastatic myoepithelial carcinoma should be included in patients presenting with multiple scalp nodules and a history of head and neck tumors. Further investigation is needed to determine which immunotherapies might benefit patients with systemic disease, and a close multidisciplinary approach involving other subspecialties is necessary to ensure optimal patient care.

References

  1. Xu T, Liao Z, Tang J, Guo L, et al. Myoepithelial carcinoma of the head and neck: a report of 23 cases and literature review. Cancer Treat Commun. 2014,2(2–3):24–29.
  2. He D, Hua C, Tang X, Feng Y. Cutaneous metastasis from the parotid myoepithelial carcinoma: a case report and review of the literature. J Cutan Pathol. 2008;35(12):1138–1143.
  3. Dimitrijevic MV, Tomanovic NR, Jesic SD, et al. Epithelial–myoepithelial carcinoma—review of clinicopathological and immunohistochemical features. Arch Iran Med. 2015;18(4):218–222.
  4. Kilpatrick SE, Hitchcock MG, Kraus MD, et al. Mixed tumors and myoepitheliomas of soft tissue: a clinicopathologic study of 19 cases with a unifying concept. Am J Surg Pathol. 1997;21(1):13–22. 
  5. Antonescu CR, Zhang L, Chang NE, et al. EWSR1-POU5F1 fusion in soft tissue myoepthilial tumors. A molecular analysis of sixty-six cases, including soft tissues, bone, and visceral lesions, showing common involvement of the EWSR1 gene. Genes Chromosomes Cancer. 2010;49(12):1114–1124.
  6. Ellens NR, Camelo-Piragua S, Ellens SM, et al. Metastasis of malignant myoepithelial carcinoma to the brain. BMJ Case Rep. 2018;2018.  

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Category: Case Report, Current Issue, Cutaneous Oncology

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