Elderly Man Develops Facial Plaque After Salivary Duct Carcinoma Diagnosis

An elderly man presented with a violaceous lesion on his face that gradually increased in size and spread to his chest, reported Chen-Yi Wu, MD, PhD, of Taipei Veterans General Hospital in Taiwan, and colleagues, who also noted blackish papules and nodules on the affected skin.

The plaque was asymptomatic, the patient said. However, it had been progressing from his left cheek to his neck and chest since it developed 3 months previously, the authors wrote in JAMA Dermatology.

The team learned that the patient had been diagnosed with primary salivary duct carcinoma of the hard palate the previous year. This was being treated with oral bicalutamide and radiation therapy. A routine follow-up x-ray assessment 3 months previously had showed partial regression of the palatal tumor.

On clinical examination, the team noted “a hemorrhagic and erythematous plaque with multiple purpuric-to-blackish infiltrative papules and nodules”; these were of various sizes and extended from the patient’s cheek to the side of his neck, to the interclavicular area.

They performed an incisional biopsy of the infiltrative nodule on the man’s cheek, and the tissue was sent to histopathology for analysis.

The lab used hematoxylin-eosin staining to assess the biopsy specimens. This “revealed a diffuse infiltrate of large, ovoid tumor cells that formed tumor nests and tumor emboli, with marked erythrocytes extravasation in the dermis,” Wu and colleagues wrote.

The cells were hyperchromatic and characterized by abundant eosinophilic cytoplasm, nuclear atypia, and pleomorphism; use of higher magnification revealed comedonecrosis. “Androgen receptor and GATA3 were diffusely strong positive in the tumor cells, while other endothelial markers, including CD31, CD34, and ERG1, were negative,” they noted.

The team diagnosed the patient with carcinoma hemorrhagiectoides caused by metastatic salivary duct carcinoma. Additional imaging detected numerous metastases in the lung, liver, and bone. They treated this with a combination of oral bicalutamide and chemotherapy with carboplatin and fluorouracil.

At the next follow-up examination 4 months later, radiography showed that the liver and lung metastases had partially regressed.

Discussion

Salivary duct carcinoma is an aggressive cancer originating in the primary salivary gland, Wu and co-authors said. It tends to have a high rate of both local recurrence and distant metastasis.

About 5% to 10% of salivary gland cancers involve the salivary duct, and often affect men over the age of 50. It typically metastasizes to the lungs and bones, the authors said; however, in rare cases, it may spread to the skin where it causes pink pebble-like papules, nodules beneath the skin, or, in rare instances such as this one, it presents as carcinoma hemorrhagiectoides.

“Carcinoma hemorrhagiectoides is characterized as a purpuric indurated plaque with overlying angiokeratoma-like black keratotic papules and nodules,” Wu and team wrote. When it affects the front of the chest, it may present as a shield sign, so-called for being shaped like a medieval knight’s shield.

Studies have suggested that carcinoma hemorrhagiectoides may develop due to “direct tumor invasion of blood vessels and lymphatic ducts in the dermis,” they noted. In this case, clinicians performed the biopsy in order to rule out other differential diagnoses. Histopathologic examination of salivary duct carcinoma generally reveals “tumor cells with abundant eosinophilic cytoplasm, large pleomorphic nuclei, and conspicuous nucleoli,” they added, with or without comedonecrosis and a cribriform pattern of growth.

As in this case, immunohistochemical analysis of the tumor cells generally reveals “a strong and diffuse positive staining for androgen receptor,” the group wrote, noting that this is true in more than 90% of cases.

Testing positive for GATA3 and GCDFP-15 with negative p63 expression also supports a diagnosis of salivary duct carcinoma. “In addition, the histopathologic and immunohistochemical profiles of metastatic SDC [salivary duct carcinoma] may closely resemble invasive ductal carcinoma of the breast,” the authors explained; thus, a thorough clinicopathological correlation is necessary to make a definite diagnosis.

In this case, clinicians considered several differential diagnoses, including radiotherapy-induced epithelioid angiosarcoma, Kaposi sarcoma, and acquired angiokeratomas.

The first is a late complication of radiotherapy, they noted, which typically develops after a median of 8 years, often in women with cancers of the breast or reproductive organs.

It is often identified when widespread purplish discoloration affects the previously irradiated skin. Pathologically, it is marked by “crowded atypical endothelial cells with nuclear atypia, necrosis, hemorrhage, [and] occasional formation of intracytoplasmic lumina,” the authors noted. In addition, test results will be positive for endothelial cell markers, such as CD31, CD34, and ERG1, they said.

As a high-grade form of angiosarcoma made up primarily of epithelioid cells with little blood vessel involvement, epithelioid angiosarcoma has a poor prognosis and should be differentiated from primary salivary duct carcinoma, noted Wu and co-authors.

Kaposi sarcoma is associated with human herpesvirus type 8 infection, and is an angioproliferative disorder that carries an intermediate risk of cancer. Kaposi sarcoma is less likely to present on the head and face; most often, it manifests as violaceous patches, plaques, or nodules on the trunk, limbs, and mucosa. The one exception to this is AIDS-associated Kaposi sarcoma.

The pathological effects of this disease vary as it progresses through different stages, the authors explained, “as characterized by slit-like spaces and a proliferation of bland spindle cells stating positive for CD31 and herpesvirus type 8.”

Finally, acquired angiokeratomas typically cause multiple hyperkeratotic papules that are blue to red in color, and widely distributed on the body. Microscopic examination will reveal “dilated vascular spaces in the dermis extending into the epidermis with hyperkeratosis, acanthosis, papillomatosis, and elongation of the rete ridges,” Wu and team wrote.