Patient presentation
A 52-year-old man presented with these asymptomatic yellowish to skin-colored growths in his genital area. He was otherwise healthy and he was not taking any medications.
His family history was unremarkable.

What is Your Diagnosis?

Diagnosis: Idiopathic Scrotal Calcinosis
Idiopathic scrotal calcinosis (ISC) is an uncommon, benign, well-defined clinical and histologic entity with an unclear pathogenesis. It has been classified as a form of idiopathic calcinosis cutis.1 The description of the first case was attributed to H. M. Lewinski in 1883.2 However, the term ISC was first introduced by Shapiro et al. in 1970.1 Most patients reported to date presented between the ages of 20 and 40. The youngest and oldest patients reported in the literature were 9 and 85 years old, respectively.3

Clinical Features
The majority of patients present with painless firm papules or nodules on the scrotal skin.4 Lesions usually grow slowly over years or even decades, ranging in size from a pinhead to several centimeters in diameter.1 The number of lesions vary from a few to more than 100. Usually hard and easily palpable, the nodules are marble-like in appearance, solitary or multiple, and may be polypoidal or pedunculated.5,6 Initial lesions are skin-colored, but with enlargement, evolve into yellowish and lobulated nodules.7 In severe cases they may lead to massive deformation of the scrotal wall.8 The lesions are generally non-tender and asymptomatic, except for occasional reports of mild pruritus, a sensation of heaviness and occasionally white chalky discharge.4,6,9 Patients are also at risk for secondary infection.

In the literature there are several case reports of atypical presentations, or patients presenting with associated features. According to one recent report, a patient presented with prostatitis-like symptoms that resolved after a simple excision.10 Another report described a patient with a solitary pedunculated tumor,6 and the term “polypoid scrotal calcinosis” was proposed for this unusual appearance.11 There are also two case reports in the literature of ISC in association with vitiligo.12,13 Of note, idiopathic calcinosis can also affect the external genitalia other than the scrotum, including the labia majora of the vulva14 and the penis.15 A woman presenting with idiopathic calcinosis of the areola of the nipple, with clinical features resembling scrotal calcinosis, was also recently reported.16

Scrotal Calcinosis: Is it Idiopathic?
The origin of ISC is still being disputed with no general consensus about the pathogenesis.5 Review of the literature reveals four main theories, which are discussed below.

1. A few authors argue that ISC results from inflammation of epidermal cysts, followed by dystrophic calcification within the keratin of the cyst or dermis adjacent to a ruptured cyst wall.3,17 This hypothesis ignores the occurrence of scrotal calcinosis without previous inflammation and the absence of epidermoid cysts in most patients.15

2. More recently, some have reported calcification of cysts of an eccrine nature, confirmed by the sweat gland marker carcinoembryonic antigen, immunohistochemical staining and electron microscopy.18,19 This may be an indication that ISC results from calcification of eccrine cysts. Based on this observation, Dare and Axelsen have suggested the name “hidrocalcinosis” as a more appropriate term for ISC.18

3. Another theory is based on the histological findings in some patients showing degenerative changes in the dartoic muscle bundle. It has been argued that this may be an initial pathogenic event, with the necrotic bundles coalescing and eventually forming dystrophic calcification.20,21

4. Of the 100 or so cases of ISC described in the literature, only 19 had evidence of a true cyst or epithelial lining surrounding the calcific nodules.4 In an investigation of 63 nodules by Wright et al., no evidence of keratin was found in the dermal tissue adjacent to the calcium deposits, and immunohistochemical stains for keratin were negative.22 The inability, in most cases, to find a pre-existing lesion has led many investigators to deduce that the condition truly is idiopathic.4, 22, 23

Of note, Onchocerca volvulus worms in the scrotum have been reported to produce lesions that clinically resemble ISC. However, this is a distinct entity.

Histology and More for the Diagnosis
Histologic examination is necessary to confirm the clinical suspicion of scrotal calcinosis. Histology reveals focal dermal collections of deeply basophilic material on hematoxylin and eosin stain, which stains black with the von Kossa stain for calcium, and red with Alizarin stain for calcium. A thin layer of granulation tissue composed of foreign-body giant cells, epithelioid cells, and connective tissue cells surrounds these deposits.4 Reports of various epithelial or cyst remnants have varied from none in most reports to many in others.4 The nodules are of varying diameters and are not attached to the underlying structures or to the overlying epidermis. The use of transmission electron microscopy has shown crystals and mineral deposits on degenerated collagen fibrils and within the cytoplasm of fibroblasts.24 Chemical analyses of the deposits show phosphate, carbonate, calcium and traces of magnesium.1 The use of infrared spectrophotometry in experimental studies has established nearly equal proportions of calcium phosphate (52%) and magnesium ammonium phosphate (48%).23

In ISC, an X-ray of the scrotum reveals numerous radio-opaque shadows of varying sizes, some of which may not be appreciated in a clinical examination.20 Serum and urinary levels of calcium phosphate, uric acid, alkaline phosphatase, parathyroid hormone, calcitonin and vitamin D are normal.7 Renal function is also normal.4

Management
Treatment of ISC is always surgical, and generally limited to excision of the affected part of the scrotal wall.8 The interval between the onset of the disease and therapy is often a period of several years,3 during which time lesions may break down spontaneously, excreting chalky white odorless material.4 Surgery is currently the optimal way to remove nodules that are pruritic, discharging white material, or when removal is desirable for cosmetic reasons.4 Removal of asymptomatic lesions may also be warranted as they typically increase in number and size.9 Calcified masses are usually located in the dermis; therefore, surgical resection should be limited to the scrotal wall.26

A novel pinch-and-punch excision technique for removing scrotal calcinosis was recently described.9 This procedure involves initially injecting 0.1% lidocaine with 1:10,000 epinephrine locally. The anesthetic, combined with gently rubbing the cysts, separates the cysts from the surrounding connective tissue and superficial scrotal (Dartos) fascia. After
10 minutes, a 2- to 4-mm disposable biopsy punch is used to incise the skin over the cyst. Small cysts can be removed with forceps, while larger lesions are squeezed out. Any residual cyst wall may be grasped with forceps and pulled out. Suture closure is usually not required, and second-intention healing is enhanced by the contractile nature of scrotal skin.

Occasionally, surgical reconstruction for massive deformity of the scrotum is required.8 A subtotal excision of the scrotal wall is the most common procedure in cases of massive calcinosis.26 Nodules clustered in one region of the scrotum can be removed en bloc with good cosmetic result.7 Primary closure is usually possible, even though non-scrotal skin may need to be used to close the defect.8 Some authors recommend the use of horizontal mattress sutures with stitches distant from each other on the same side of the incision as the best way to close the incision.26 When most of the scrotum is involved, total scrotal skin removal and grafting may be necessary.27

More Studies Needed
ISC is an uncommon disorder of unknown cause, and further studies are needed to establish causality and pathogenesis.5 Treatment is surgical, usually with satisfactory cosmetic results. Although recurrence after surgical excision is unusual, three patients have been reported with recurrent asymptomatic nodules.10

Disclosure: The authors have no conflict of interest with any subject matter discussed in this month’s column.