Apocrine hidrocystoma is a benign cystic tumor arising from the secretory portion of apocrine sweat glands. It was first reported by Mehregan in 1964 and described as a cystic proliferation of apocrine sweat glands in the head and neck region1). It is not just a simple retention cyst of secretions, but is regarded as an adenomatous neoplasm of the apocrine glands1)5).
In the eyelid, it originates from the Moll gland, a modified apocrine gland. Common sites include the scalp, face, axilla, external auditory canal, eyelid, and groin, which are areas rich in hair follicles1).
It most often affects adults aged 30 to 70 years, with no sex difference1). It is rare in children and adolescents5). Most cases are solitary, but in multiple cases an association with Schopf-Schulz-Passarge syndrome and Goltz-Gorlin syndrome has been reported2)5).
Apocrine hidrocystoma is derived from apocrine glands, and eccrine hidrocystoma from eccrine glands. The apocrine type is usually solitary, 3 to 15 mm in size, and tends to occur in areas rich in hair follicles. Histologically, they are distinguished by the presence or absence of decapitation secretion and lipofuscin granules.
Apocrine hidrocystoma is usually asymptomatic. When it occurs on the eyelid, it may cause the following symptoms.
Although apocrine hidrocystoma itself is benign, it must be distinguished from malignant tumors such as basal cell carcinoma and amelanotic melanoma. Because a definitive diagnosis can be difficult based on clinical findings alone, if a cystic mass is found on the eyelid, it is advisable to see an ophthalmologist and undergo histological examination.
The cause of apocrine hidrocystoma is not fully understood. The main hypothesis is neoplastic proliferation due to dysregulation of apocrine sweat gland secretory cells, and it is considered an adenomatous neoplasm rather than a simple retention of secretions1)5).
The proposed explanations for its development are as follows.
No clear predisposing factor has been established, and there are no records of spontaneous regression5).
It may be suspected from its appearance (bluish color, dome shape, mobility, and transillumination), but there are limits to the accuracy of clinical diagnosis. Even when it is diagnosed as a hidrocystoma before surgery, histology may show cystadenoma (proliferative type), or it may be mistaken for an epidermoid cyst4).
Histopathological examination by excisional biopsy after removal is essential for definitive diagnosis. The excised tumor must always be fixed in formalin and diagnosed under a microscope.
The main histologic findings are as follows.
The proliferative type (cystadenoma) and non-proliferative type are distinguished based on Sugiyama et al.’s classification4).
Proliferative type (cystadenoma)
True papillae: Papillary projections with a vascular connective tissue core are seen.
Adenomatous hyperplasia: Shows proliferative changes within the lumen.
ER/PR positive: Estrogen and progesterone receptors are positive in about 80% of cases4).
Non-proliferative type (sweat cyst)
Pseudopapillae: Only pseudopapillae without a connective tissue core are seen.
Simple cyst: No intraluminal proliferation.
ER/PR negative: Hormone receptors are usually negative4).
Immunohistochemistry shows CK7 positivity and p63 positivity (myoepithelial cells)5).
The main differential diagnoses are shown below.
| Differential diagnosis | Key distinguishing points |
|---|---|
| Eccrine hidrocystoma | Derived from eccrine glands. Often multiple |
| Basal cell carcinoma | Malignant. Pearly appearance, ulceration |
| Amelanotic melanoma | Malignant. Rapid enlargement, telangiectasia |
Cystic lesions with high T2 signal may be misdiagnosed as cavernous hemangioma2). If internal septa are present, differentiation from epidermoid cyst is also an issue4). Definitive diagnosis by MRI alone is difficult, and histopathological examination is ultimately required.
Complete surgical excision with a narrow margin is the first choice1)2). It can be performed under local anesthesia1)4), and prognosis is excellent when the lesion is completely removed. Recurrence has been reported after incomplete excision2).
If the cyst wall is likely to rupture, an intraoperative technique has been reported in which fibrin glue mixed with fluorescein (or indocyanine green, trypan blue, or methylene blue) is used to fill the cyst and help confirm the excision margin2).
Small, asymptomatic lesions may also be observed2).
Surgical excision
Indications: Symptomatic lesions, or lesions that need a definite diagnosis.
Method: complete excision under local anesthesia with a narrow margin.
Recurrence rate: minimal with complete excision.
Advantages: a definitive diagnosis can be obtained at the same time.
Alternative therapies
Needle puncture: simple, but the cyst wall remains and the recurrence rate is high1)5).
Sclerotherapy: injection of hypertonic glucose into the cyst1)2).
Trichloroacetic acid: effective for lesions up to 15 mm2).
CO2 laser vaporization: suitable for multiple scattered lesions2)5).
Other alternative treatments reported include botulinum toxin A1), needle puncture after topical application of 1% atropine cream or scopolamine cream5), and electrosurgery5).
With needle puncture, the cyst contents can be drained, but because the cyst wall remains, fluid collects again and recurs. Complete removal of the cyst wall is the key to preventing recurrence, and surgical excision is recommended1)5).
Apocrine hidrocystoma develops due to adenomatous cystic proliferation of the secretory portion of the apocrine sweat gland. It is not simply a retention cyst of secretions, but an adenomatous neoplasm1)5).
The cyst wall consists of a bilayered epithelium (secretory inner layer + myoepithelial outer layer), reflecting its apocrine gland origin. The secretory epithelium of the inner layer shows decapitation secretion characteristic of apocrine glands. The apical portion of the cell protrudes to form an apical snout and is shed as part of the secretion process1)2)3).
The cyst fluid contains lipofuscin granules (PAS-positive), which are the cause of the blueish color seen clinically1)5).
In the proliferative type (cystadenoma), papillary and adenomatous intraluminal proliferation is seen, and true papillae with a vascular connective tissue core are formed4). About 80% of proliferative cases are positive for estrogen receptor (ER) and progesterone receptor (PR), whereas non-proliferative cases are negative4). These findings suggest involvement of a hormone-dependent proliferative mechanism.
A possible multistep progression from hidrocystoma to cystadenoma to endocrine mucin-producing sweat gland carcinoma has been suggested4).
A distinction between proliferative type (cystadenoma) and non-proliferative type based on Sugiyama et al.’s classification has been proposed4). The presence or absence of true papillae with a connective tissue core serves as the basis for classification.
Al Ghulaiga et al. (2024) reported four cases of periocular apocrine cystadenoma and showed that three cases clinically diagnosed as hidrocystoma before surgery were histologically proliferative type (cystadenoma). ER/PR were strongly positive in 80% of proliferative type cases, confirming biological differences from the non-proliferative type4).
It has been suggested that the proliferative type (cystadenoma) may be a precursor lesion to endocrine mucin-producing sweat gland carcinoma4). Future work should stratify malignancy risk by ER/PR immunostaining.
Systematic evaluation is underway of the effectiveness and recurrence rates of minimally invasive treatments such as CO2 laser ablation, hypertonic glucose sclerotherapy, and trichloroacetic acid injection2).
Huang et al. (2022) reported an intraoperative marking technique in which fluorescein was mixed with fibrin glue to fill the cyst, showing that it is useful for confirming complete excision2).
Sahu et al. (2023) reported the first case of an apocrine sweat cyst along the nasolacrimal duct3). Differentiation from lacrimal sac cysts, dermoid cysts, and lacrimal sac mucoceles is important, and more cases at this site need to be accumulated.
