Nodular Mucinosis of the Breast: A Case Report With Pathologic, Ultrasonographic, and Clinical Findings and Review of the Literature Open Access

Nodular mucinosis of the breast is an extremely rare lesion.1,2 It was first described by Wee et al3 in 1989 in a 20-year-old Chinese woman and was called nerve sheath myxoma of the breast. Following this report, a few more cases have been described.4,5 Carney syndrome is an autosomal dominant trait in which patients may develop myxomas of the skin and subcutaneous tissues, especially at the skin-mucosal junctions of the nipple, eyelids, labia majora, and prepuce, in addition to myxoid fibroadenomas. The condition may also manifest with myxomas of the heart, spotty skin pigmentation, endocrine overactivity (Cushing syndrome, acromegaly, or gigantism), psammomatous melanotic schwannoma, and testicular tumors.2,3,6,7 In patients without Carney syndrome, however, nodular mucinosis characteristically arises in the nipple.2 The myxoid appearance of this lesion is due to abundant stromal acid mucopolysaccharide, which stains strongly positive with Alcian blue and Hale colloidal iron. The myxoid lesion will not stain, however, by periodic acid– Schiff stain, a biochemical stain for neutral mucopolysaccharides. The purposes of this article are to report a case of this extremely rare beast lesion and discuss its pathologic, ultrasonographic, and clinical features and to review the literature.

A 21-year-old white woman presented with a mass in the left breast for a duration of 6 months. She had never been pregnant or had any history of breast feeding, surgery, trauma, or use of exogenous hormones. Her social history was significant for a history of smoking of 1 pack-year and moderate use of caffeinated beverages. Her medical history was significant for epilepsy without taking any medication. Her family history was negative for breast cancer. Clinical breast examination demonstrated a 1-cm “rubbery” mass directly under and continuous with the left nipple. The skin that covered the mass had an edematous and irregular appearance without erythema or drainage from the nipple. There was mild nipple tenderness on palpation, without evidence of nipple retraction or skin changes. The right breast, including the nipple, was normal. Ultrasonography demonstrated a 1-cm, nonintraductal, circumscribed, homogeneous, isoechoic mass that was continuous or part of the base of the left nipple. The mass was smooth, with a thin echogenic rim (Figure 1). Doppler flow showed some vascularity. Differential diagnosis included a benign breast mass such as a fibroadenoma or nipple adenoma. Because of the patient's age and a negative family history of breast cancer, a mammogram was not performed. Despite reassurance, the patient desired excision of the lesion.

Gross examination of the specimen demonstrated a rubbery-firm, ovoid, pink, polypoid mass that measured 1.5 × 0.9 × 0.8 cm, covered by an ellipse of overlying normal skin. Sectioning of the mass revealed a variegated, slightly nodular, grayish pink cut surface. The specimen was submitted entirely for microscopic examination.

Histopathologic evaluation of the lesion showed a well-circumscribed, nonencapsulated tumor with a slight nodular appearance, which consisted of an accumulation of pink myxoid tissue that contained spindle cells that showed bland-appearing nuclei with no mitosis and low to moderate cellularity (Figure 2). The pink myxoid tissue demonstrated strong staining with Alcian blue (pH 2.5) (Figure 3, A), which was removed by pretreatment with hyaluronidase (Figure 3, B). Hale colloidal iron stain showed intense bluish staining of the myxoid tissue. The spindle cells were positive for vimentin and smooth muscle actin (Figure 4) and negative for smooth muscle myosin, cytokeratin (AE1/AE3), and S100.

Mucinosis of the nipple was first described by Wee et al3 in 1989 in a 20-year-old Chinese woman and was named nerve sheath myxoma of the breast. Following this report, a few more cases have been described. The common features in clinical presentation of these lesions include a poorly circumscribed, slowly growing mass, which is usually lobulated, soft, and located under the nipple. Ultrasonography usually revealed a well-circumscribed, lobulated, homogeneous, hypoechoic mass. Mammogram revealed a lobular, radiopaque mass without microcalcification and spicules. Differential diagnosis among mammary nodular mucinosis, mucinous carcinoma, myxoid fibroadenoma, myxoid neurofibroma, and mucocele solely based on radiologic examination may be difficult.5 Fine-needle aspiration shows mucin with no evidence of malignancy or epithelial components. The lesion grossly is well circumscribed but not encapsulated, is glistening, and has a myxoid nodular appearance; microscopically, it is made up of multiple nodules in various sizes. The nodules contain abundant myxoid matrix and scattered fibroblasts with small, bland-looking, elongated nuclei, pale cytoplasm, and indistinct borders. The nodules are separated from each other by fibrous septae that contain delicate blood vessels. Scattered lymphocytes, plasma cells, and mast cells are seen within and around the nodules. The tumor does not invade the breast ductules, lobules, or skin appendages, and no epithelial components are seen within the nodules. The myxoid component of the mass is composed of acid mucopolysaccharide, and it stains strongly positive with Alcian blue and Hale colloidal iron and does not stain with periodic acid–Schiff. This finding confirms the acidic nature of this stromal myxoid component.8 In ultrastructural studies of the spindle cell component, Wee et al3 and others4,5 concluded that the tumor probably arises from a primitive mesenchymal cell. A long-term follow-up (6 years) in a previous study9 confirmed the benign nature and persistence of subareolar mucinosis with no histopathologic changes over the years.

Nodular mucinosis of the nipple should be differentiated from other mucinous or myxoid breast lesions. Superficially located myxoid fibroadenomas of the breast, which occur near the nipple in young women, are usually well circumscribed and may show a lobular pattern; however, myxoid fibroadenoma usually involves the mammary ducts. In addition, myxoid fibroadenoma consists of a mixture of epithelial and myoepithelial cells, which are positive for cytokeratin and calponin, respectively.10 Patients with Carney syndrome may develop myxoid fibroadenomas and myxomas of the skin and subcutaneous tissues, especially at the mucocutaneous junctions of the nipple. The breast myxomatosis in Carney syndrome is usually associated with ductal adenoma.7 The presence of other clinical signs of Carney syndrome, including skin pigmentation, which usually is present since birth, and also the presence of a family history is helpful in the diagnosis. Carney syndrome is an autosomal dominant trait that has been linked to 2 genes: a chromosome 2 (2p15– 16) locus and a chromosome 17 (17q22–24) locus.7 Myxoid neurofibroma usually does not have a lobular pattern and has a fibrillary background. Careful searching of the lesion may show features of neural differentiation, and immunohistochemical staining with S100 shows scattered positivity. Myxoid liposarcoma has a vascular plexiform capillary pattern, and lipoblasts are seen within the tumor, which show positivity for S100. Myxoid variant of malignant fibrous histiocytoma is recognized by its storiform pattern and large, pleomorphic malignant histiocytes.3 Mucocele-like tumors of breast, first described by Rosen,11 represent a group of cystic lesions characterized by extension of mucinous contents into the mammary stroma. These cystic tumors range from benign to low-grade mucinous carcinomas. Mucocele-like tumors are considered to result from rupture of ducts distended by a substantial amount of mucus, with dissection of mucus into the stroma.11 They may be accompanied by atypical ductal hyperplasia, intraductal carcinoma, which is usually of the micropapillary or less often cribriform type, or mucinous carcinoma.12 Micropapillary carcinoma in situ usually produces excessive mucin, causing rupture of the distended ducts.13 In the absence of epithelial cells, histopathologic analysis with consecutive sections may disclose the nature of underlying lesions. The presence of rare cancer cells in the extravasated mucin is more controversial, since a mucocele-like tumor occurs when ducts that contain micropapillary carcinoma in situ fill with mucin, and it may rupture with extravasation of mucin into the mammary stroma. Whether the presence of cancer cells in the extravasated mucin is biologically equivalent to tumor invasion is controversial.13 In addition, mucocele-like lesions are usually associated with microcalcification, which is a feature not seen in nodular mucinosis.14 Mucin in mucocele-like lesions usually stains strongly with periodic acid– Schiff and mucicarmine, contrary to mucin in nodular mucinosis, which is usually stained with Alcian blue and Hale colloidal iron.5 Mucinous carcinomas are differentiated by the presence of malignant epithelial cells within the lesion, which are positive for cytokeratin by immunohistochemical studies.4,5 

Because of the superficial location of nodular mucinosis of the breast, it also should be differentiated from cutaneous follicular mucinosis. Follicular mucinosis of skin has 2 subtypes. The first is seen most commonly in children and is called alopecia mucinosa. In this condition, mucin is present in the hair follicles, accompanied by near-complete loss of hair shaft and perivascular or perifollicular lymphocytic response. In the second type, which is associated with cutaneous T-cell lymphoma, the lesion is nodular or plaquelike. In this pattern, there is a dense linear infiltrate of abnormal lymphocytes with hyperchromatic and cerebriform nuclei in the papillary dermis with tropism to overlying epidermis.15 In conclusion, this rare, benign breast lesion need to be correctly recognized and differentiated from other allied myxoid or mucinous mammary tumors, in particular, malignant mucinous neoplasms.