Report of a case: Primary mucinous carcinoma of the skin
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Report of a case: Primary mucinous carcinoma of the skin
Brent C Kelly MD1, Jeannine Koay MD2, Marcia S Driscoll MD3, Sharon S Raimer1, Maria I Colome-Grimmer MD1
Dermatology Online Journal 14 (6): 4
1. University of Texas Medical Branch, Galveston, TX. bckelly@utmb.edu2. Private Practice, Dallas, TX
3. Private Practice, TX
Abstract
Primary mucinous carcinoma of the skin is an extremely rare adnexal tumor that is thought to originate from eccrine sweat glands. The neoplasm usually arises on the head and neck, with the most commonly involved area being the periorbital region. The tumor is typically a solitary, asymptomatic nodule, cyst, or ulcer that is slow growing with low metastatic potential. However, post-excisional local recurrence is common, affecting up to 36 percent of patients. Since primary mucinous carcinoma of the skin is such a rare neoplasm (<130 cases have been reported to date), a complete workup should be conducted to rule out other internal malignancies that may metastasize to the skin. We report a case of primary mucinous carcinoma of the skin, and discuss the clinical presentation, histology, treatment, course, and prognosis.
Case report
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A 52-year-old man presented in October, 1996, with a slowly enlarging, asymptomatic nodule involving the right eyebrow. A similar lesion had been excised one year previously and was clinically diagnosed as a "cyst," per patient report. Previous pathology reports and tissue were not available for review. Examination revealed a 0.9 cm shiny, firm nodule within the region of the right eyebrow (Fig. 1).
An excisional biopsy was performed and microscopic examination of the specimen showed dermal nests of tumor cells lying within "pools" of pale-staining mucin (Fig. 2). The mucin was separated by thin fibrous septa and occasional duct-like structures were present. Positive stains with periodic acid-Schiff both with and without the presence of diastase (Fig. 3) and positive staining with mucicarmine (Fig. 4) suggested the mucinous material to be of epithelial origin consistent with sialomucin. Alcian blue and colloidal iron also positively stained the mucinous material. The tumor cells were cuboidal with eosinophilic cytoplasm. They were relatively uniform in size and shape with very little atypia or evidence of mitoses. Additionally, immunostaining showed the tumor cells to be positive for CK7, but negative for CK20—an important distinction from metastatic colorectal tumors. The tumor was also negative for prostate specific antigen (PSA). Based on the histologic findings, the diagnosis of primary cutaneous mucinous carcinoma was made. Tumor margins were positive, and the patient was to follow-up in a dermatology clinic to discuss the need for further excision.
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During the same time that the patient was diagnosed with mucinous carcinoma of the skin, he was also being worked up for an elevated PSA of 9.7 ng/mL. Biopsy of the prostate revealed prostatic adenocarcinoma (Gleason score of 6) and the patient underwent radical perineal prostatectomy in January, 1997. His prostatic adenocarcinoma was not of the mucinous type and histologically did not resemble the eyelid tumor. Follow-up PSA decreased to 0.4 ng/mL. To rule out metastatic prostate adenocarcinoma, the patient had a full workup that included chest x-ray; computed axial tomography (CT) of the chest, abdomen, and pelvis; and total body bone scan. All tests were negative.
Because of his recently diagnosed prostate cancer, the patient neglected to follow up with his dermatology appointments. He returned to clinic in June, 1997, complaining of a new lesion near the previous biopsy site. On physical exam a 0.5 cm well-healed scar was present within the right lateral eyebrow. Just medial to the scar a 0.4 cm firm skin-colored papule was noted. Both lesions were biopsied and histologic examination revealed no residual carcinoma at the site of previous biopsy. However, the new papule located just medial to the scar was positive for mucinous carcinoma. The patient was referred to the otolaryngology department for wide local excision.
A thorough search for internal malignancy was advised to rule out other primary neoplasms that may have metastasized to the skin. The patient received most of the necessary studies as concomitant work-up for his prostate adenocarcinoma—chest x-ray, CT of the chest, abdomen, and pelvis, cystogram, and total body bone scans, in addition to colonoscopy and endoscopy. Laboratory evaluations were within normal limits and included hemoglobin, renal, and liver function studies, and a coagulation profile. Aside from his prostate cancer, no other malignancies were detected. The patient was contacted by telephone in June, 2006. He was employed, well, and receiving his health care at another university. He reported no recurrence of prostate cancer. Although the patient agreed to return to our clinic for further evaluation, he did not keep his appointment and was subsequently lost to follow up.
Comment
Mucinous carcinoma is a rare primary skin neoplasm of sweat gland origin, with relatively few cases described in the literature [1, 2]. Because of its rarity, an affirmative diagnosis cannot be made until further investigation has ruled out other primary malignancies of other organs that may produce mucin and metastasize to the skin, specifically, breast, gastrointestinal tract, lung, kidney, ovaries, pancreas, and prostate [3-5]. Metastatic lesions from the breast or colon are most likely to mimic mucinous carcinoma of the skin [6].
Most patients with primary mucinous carcinoma of the skin are older individuals with an average age at occurrence of 61 years (range 8 to 84 years). There is an increased predilection in men, with white (62%) and black (34%) patient populations being the most commonly affected [7]. The vast majority of tumors are located on the head and neck, although they may arise on any area of the body. Interestingly, almost half of all tumors are located periorbitally [8, 9].
Clinically, patients usually present with small, solitary, asymptomatic papules or nodules that have been present for several years. There are no specific clinical findings that are particularly characteristic of mucinous carcinoma; the clinical appearance may vary from patient to patient. Initial clinical evaluation generally yields a differential diagnosis that includes epidermoid cyst, hidrocystoma, pyogenic granuloma, melanoma, sebaceous carcinoma, cystic basal cell carcinoma, squamous cell carcinoma, neuroma, lacrimal sac tumor, pilomaticoma, hemangioma and lipoma [1, 7, 10]. Tumors rarely metastasize, but the local recurrence rate is high [11]. Regional metastasis occurs at a rate of 5 to 15 percent and distant metastasis occurs in only 2 to 7 percent of affected patients [8]. Patients have been described who have had a lesion for many years without seeking treatment and yet still rarely experience symptoms or evidence of metastatic disease. Occasionally, longstanding neoplasms or more aggressive tumors may invade into adjacent structures [12]. The generally benign, slow-growing course of mucinous carcinoma is hypothesized to be correlated with the production of mucin, which may correlate with a high degree of cellular differentiation. Additionally, the presence of copious amounts of mucin may serve as a physical barrier to spread, compressing the tumor stroma and restricting growth, as well as inhibiting DNA synthesis and, hence, decreasing the rate of angiogenesis [4, 13].
Although the clinical presentation of mucinous carcinoma is nonspecific, the histologic and pathologic examination is very characteristic. Tumors are generally well circumscribed with small islands or tubules of epithelial cells floating in large pools of mucin. The mucin is separated by thin fibrocollagenous septa and is positively stained with periodic acid-Schiff (PAS), mucicarmine, alcian blue at pH 2.5, and colloidal iron [14]. The mucin has been characterized as sialomucin and is PAS positive both with and without the presence of diastase or hyaluronidase. It is, however, sialidase-labile. Cells are small, cuboidal and vacuolated with eosinophilic cytoplasm. Mitoses and cellular pleomorphisms are rare [15].
It has been suggested that primary mucinous carcinoma of the skin may develop as a progression from abnormal apocrine or eccrine ducts, analogous to the progression seen in mucinous carcinoma of the breast. A ductal in-situ component can occasionally be seen ranging from ductal hyperplasia to frank carcinoma in-situ. It is not clear if these "mixed" mucinous carcinomas have a more aggressive course than their breast counterparts [20]. Rosai originally suggested that the ductal proliferation continues until the overproduction of mucin results in islands of tumor cells breaking off and 'floating' in the mucinous pools [21].
Differentiating primary mucinous carcinoma from metastatic tumors, particularly of gastrointestinal or breast origin, can be difficult. The absence of expression of CK20 by immunohistochemical staining may exclude the diagnosis of metastatic colorectal mucinous carcinoma [6]. Differentiating from breast carcinoma, can be more difficult. It is important to recognize, however, that the likelihood of mucinous carcinoma from the breast meatastasizing to the skin (much less the face or eyelid) is exceedingly low. In a large review of cutaneous metastases, Brownstein, et al. found that only 6 percent were located on the face [19]. Additionally, Rasmussen showed that only 2 of 95 cases of primary mucinous breast carcinoma metastasized to lymph nodes that were histologically-identical to the primary tumor [17]. Cases of primary mucinous carcinoma of the skin have been found to be estrogen receptor, progesterone receptor, and GCDFP-15 positive. Qureshi, et al. suggest that finding an in-situ component of tumor that stains for myoepithelial cells (positive stains for p63 and CK5/6 among others), can help to exclude metastatic mucinous breast carcinoma [18].
Treatment of mucinous carcinoma entails local excision. Because of the high rate of recurrence, adequate excision with generous margins (at least 1 cm) is recommended. Several reports of successful treatment using Mohs micrographic surgery have been described. One successfully treated case used low-molecular weight immunostaining in the Mohs's sections [16]. Other treatments, such as chemotherapy and radiation, generally are not employed in the management of these tumors [10]. Patients should be counseled about the importance of frequent follow-up, for evaluation for local tumor recurrence or development of regional lymphadenopathy [7].
The patient we describe is one of the few cases of primary mucinous carcinoma of the skin. The history of previous excision and local recurrence, the clinical appearance, the periorbial location, and the histologic findings are all consistent with mucinous carcinoma. Significantly, the patient underwent complete systemic evaluation for other internal malignancies that may manifest as metastatic disease to the skin, but the work-up was negative. Although the patient had prostate cancer, which may very rarely present as mucinous carcinoma, he was diagnosed with prostatic adenocarcinoma, without mucin production. Additionally, prostate cancer generally does not metastasize to the face. The fact that the patient is well, without evidence of metastatic disease nine years after the initial diagnosis of prostatic carcinoma, also makes the possibility of his initially having had metastatic adenocarcinoma unlikely. Moreover, his cutaneous tumor did not reveal PSA on immunohistochemistry. Thus, the cutaneous neoplasm appears to be a primary tumor arising from the skin.
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