While uncommon, the diagnosis and treatment of cutaneous adnexal tumors such as spiradenocarcinoma are incredibly important for prognostic implications.
Spiradenocarcinomas are rare, malignant eccrine tumors typically arising from precursor spiradenomas. Spiradenomas may arise spontaneously or as a component of a tumor syndrome, most notably familial eccrine spiradenoma or Brooke-Spiegler syndrome (BSS).1 BSS is an autosomal dominant condition in which patients develop a triad of benign adnexal neoplasms consisting of cylindromas, trichoepitheliomas, and spiradenomas localized to the head and neck.2 While these adnexal neoplasms are usually benign, malignant degeneration should be suspected in patients reporting exquisite tenderness, rapid growth, ulceration, or bleeding.2,3 Following sampling of a suspicious lesion, histologic identification of malignancy can be challenging due to the subtle nature of this tumor. Despite this, accurate diagnosis and appropriate treatment are critical to the patient’s prognosis.
We report the case of a woman who developed spiradenocarcinoma of the eyebrow within a benign spiradenoma and discuss the diagnostic and therapeutic regimens for this rare malignancy.
A 54-year-old woman with a past medical history of multiple cylindromas, spiradenomas, and clinically diagnosed BSS presented for evaluation of a new lesion of the right eyebrow. Physical examination revealed a tender, red-to-violaceous nodule in the right medial eyebrow (Figure 1). A shave biopsy revealed a blue tumor island of biphasic cells suspended within an eosinophilic stroma, with an abrupt transition to hyperchromatic, atypical, mononuclear cells with loss of the eosinophilic stroma and a predominance of ductal structures (Figures 2, 3).
Due to the aggressive nature of this tumor, the patient was referred to a regional cancer center for evaluation. Surgical oncology performed complete surgical excision of the lesion; no imaging was recommended or performed. At postoperative month 9, the right medial eyebrow displayed no evidence of recurrence. In biannual examinations over the subsequent year, the patient had multiple cylindromas and spiradenomas biopsied and excised, but none developed additional carcinomas. The patient declined to see a geneticist, though evaluation and counseling were recommended multiple times.
Spiradenocarcinoma, also known as malignant eccrine spiradenoma, is a rare eccrine adnexal tumor with only 120 reported cases in the literature.1,3,4 Affecting men and women equally, this neoplasm arises most commonly in septuagenarians.1 While most cases develop via malignant degeneration of existing spiradenomas, de novo formation has been reported.3,4 Benign and malignant lesions are both more frequent in patients with BSS or familial eccrine spiradenoma, owing to the increased incidence of folliculosebaceous-apocrine tumors seen with these conditions.2 Clinical features suspicious for malignant degeneration have been reported in lesions with a duration from 2 months to 80 years, with the average lesion duration of 6.5 years when spiradenocarcinoma is identified.1 Concerning features on examination include a chronic lesion that changes character with sudden rapid growth, erythema, tenderness, ulceration, bleeding, and satellite nodules. For this reason, many alternative and more common differential diagnoses are generally considered before spiradenocarcinoma.3 While previously theorized that the head, neck, or trunk were favored sites for tumor development, recent literature suggests there is no predilect area and that these neoplasms may arise from any eccrine gland-bearing skin.1,5
Histologically, the presence of benign spiradenoma within the sample is requisite in making the diagnosis of spiradenocarcinoma.6 Benign spiradenomas consist of multiple, sharply demarcated, dense nests of deeply basophilic cells in the dermis.7 The cells are biphasic in nature: large inner cells with vesicular nuclei are surrounded by small, peripheral cells with hyperchromatic nuclei and scant cytoplasm.7,8 Transformation to malignancy is seen with loss of the biphasic cell population. This results in sheets of basaloid cells exhibiting increased mitotic activity with pleomorphic nuclei and abundant cytoplasm.7 Ductal expansion and proliferation, necrosis, and dilation of tumoral blood vessels and invasion into other structures may also be observed.7 The abruptness of malignant transition is analogous to the grading of the tumor, with high-grade spiradenocarcinomas correlating to a stark differentiation toward malignancy.5,9,10 High-grade characteristics portend a more aggressive behavior, with a poor effect on prognosis.5,6,9,10 While our patient’s histology exhibited an abrupt transition to malignancy and a predominance of ductal structures, tumor grading was not reported.
Immunohistochemistry offers little in differentiating benign from malignant spiradenomas. Previously, it was thought that malignant cells show increased expression of the tumor suppressor protein, p53.11 This consideration has been called into question, as recent evidence shows elevated p53 levels are associated with increased stability, rather than mutation, of the protein.7 Therefore, p53 levels are not generally useful in identifying spiradenocarcinoma.7,10,12 Similarly, use of the Ki-67 proliferative index to detect malignancy has been controversial. Huang et al7 showed reliably higher levels of Ki-67 in malignancy, but van der Horst et al10 cautioned against the use of Ki-67 after finding minimal differences between levels in benign vs malignant specimens. On a more promising note, MYB, a transcription factor involved in cell proliferation, differentiation, and apoptosis, appears to be lost in malignant transformation.10 At this time, absence of MYB appears to be the most consistent and useful immunohistochemical tool for diagnosing spiradenocarcinoma.
It is paramount for clinicians to recognize features of malignancy in these neoplasms, as they may carry a high rate of recurrence, metastasis, and disease-related death.7 Tumor recurrence occurred in 17.4% of cases in a recent review by Staiger et al.1 Metastatic disease has been identified in 19% to 35% of patients, with disease-related mortality ranging from 10.2% to 22%.1,6,8 When metastasis occurs, the lungs, bones, and lymph nodes are the most commonly afflicted sites.1
Once the diagnosis is made, presurgical planning recommendations include magnetic resonance imaging to assess the extent of tumor burden, as well as fluorodeoxyglucose positron emission tomography-computed tomography for the detection of metastases.1 Treatment of spiradenocarcinoma consists primarily of surgical excision, with a lower risk of recurrence and death in cases that have been fully resected with tumor-free margins.1 The literature does not reproducibly identify a recommended surgical margin. Mohs micrographic surgery has been utilized in small reports, which allows for direct tumor visualization and extirpation while maximizing healthy tissue conservation.13-15 Patients with suspicious lymph nodes on imaging should have regional lymphadenectomy performed.1 In unresectable or inoperable cases, adjuvant chemotherapy and radiation have been used with limited results.1,3 Due to recurrence rates ranging from 19% to 59%, frequent clinical follow-up for patients diagnosed with spiradenocarcinoma is recommended.1,6,8,10 While no formal guidelines for follow-up exist, we recommend that scheduled monitoring be performed similarly to a melanoma diagnosis.
Spiradenocarcinoma is a challenging entity to recognize and diagnose, especially in a patient with multiple neoplasms in the setting of BSS. Patient prognosis and survival hinges on careful clinical suspicion and histologic recognition of spiradenocarcinoma. Though our patient was diagnosed with high-grade spiradenocarcinoma, which carries higher rates of recurrence and metastasis, she continues to be tumor free after more than 1 year.
This case underscores the need for clinicians to consider uncommon adnexal tumors in the appropriate clinical setting, as rapid identification and treatment of these neoplasms may have dramatic prognostic implications.
Dr White is a fourth-year dermatology resident at HCA Healthcare/USF Morsani College of Medicine in Largo, FL. Ms Kolodziejczyk is a fourth-year medical student at the College of Osteopathic Medicine at Rocky Vista University in Parker, CO. Dr Witfill is an assistant clinical professor of dermatology at HCA Healthcare/USF Morsani College of Medicine.
Disclosure: The authors report no relevant financial relationships.
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