The Idiopathic Scrotal Calcinosis Biology Essay
Background: Scrotal calcinosis is a rare and benign condition characterized by multiple calcific deposits occurring in scrotum and formed nodules and lumps within scrotal skin with any systemic metabolic disorder. The so-called idiopathic scrotal calcinosis does not appear to be idiopathic, but rather a process of dystrophic calcification of epidermal cysts. Histological examination shows calcium deposites with in the dermis, that may be surrounded with histiocytes and an inflammatory giant cell reaction.
Aim: To detect dystrophic calcification of epidermal cysts and to take attention to the incorrect terminology of "idiopathic calsification".
Methods: This is a two-centered study of scrotal calcinosis with 17 cases, on which clinical and histopathological examinations were conducted.
Results: The patients we examined all had scrotal epidermoid cysts in varying stages of inflammation coexisted with scrotal calcinosis. Some cyts (52.9%) had intact epithelial walls, others (35.2%) showed rupture of their epithelial walls associated with the presence of keratin fibers and calcium granules in the surrounding dermis and all had naked calcium deposits lying in the dermis .
Conclusions: The spectrum of the changes that we experienced in the histology, coupled with the normal values in the biochemical profile, shore up the theory of dystrophic calcification of epithelial cysts. In a period of time these cysts firstly become inflamed than rupture and finally calcium depocytes replase with the cysts.
Keywords: dystrophic calsification, epidermal cyst, scrotal calcinosis, scrotum
Scrotal calcinosis (SC) is a rare and benign condition that shows multiple different sizes calcified nodules within scrotal skin and without any phosphor/calcium metabolism anomaly (1,2). SC affects mainly in 20 – 40-year-old men but similar lesions named as ‘vulvar calcinosis’ has been reported in a female (3).
Multiple scrotal nodules could be seen in most patients, and the nodules are hard and yellowish or white, with various sizes from several millimeters to cantimeters. Almost all of the patients are asymptomatic just few patients may complain from the pruritus, ulcerations, and discharge of chalky material (1). Histologically, SC is characterized by the presence of calcium deposits that show variable sizes within the dermis, often surrounded by a foreign body-type granulomatous reaction (1). The exact pathogenesis is still unknown and there is a few theories for the origin include idiopathic calcification occurring within normal scrotal collagen (2), dystrophic calcification of inflamed scrotal epidermoid cysts (3), eccrine duct milia (4) or dartoic muscle, (5) and calcification secondary to minor trauma of the scrotum (6). In published material on this topic, the biochemical analysis, and serum electrolyte analysis have been found normal (2). Shah and Shet has recently reviewed the condition with 20 cases and, they claim that the etiology is dystrophic calcification (7). Despite the controversy about the origin of this entity, surgery is the best treatment that provides excellent results (8).
This two centered study of 17 cases attempts to establish dystrophic calcification of epidermal cysts and to take attention to the incorrect terminology of "idiopathic calsification".
Material and Methods
The present two-centered study was retrospective and conducted over a period of 7 years at Ankara University Medical Collage and Çankırı State Hospital. Nine of the 17 cases had not any clinical diagnose 8 of them had clinically suspected as scrotal calcinosis. Clinical and biochemical findings including serum calcium, serum phosphorus and serum alkaline phosphatase of the patients’ were noted. The tissue, after being fixed, was partially decalcified in 10 % HCl solution then routinely, embedded in paraffin, and sections were stained with hematoxylin and eosin stain. Statistical analysis was performed by the SPSS 15 Statistical Package for Word. A p value less than 0.05 was considered as significant.
The patients age was ranged from 20 to 84 years, with a mean age of 33.7 years. Scrotal calcinosis was detected incidentally in 9 patients (52.9%). Eight patients (47.1%) were symptomatic. The most common symptoms were scrotal swelling (n=3, 17.6%) and pruritus (n=3, 17.6%). Chalky discharge and ulceration were present in the same percentage (5.8%).
Mostly, lesions were multinodular and the maximum number of lesions was 24. The diameter of the largest lesion in each patient was recorded and it varied from less than 1 mm to a large mass with a size of 0.8 x 1.4 cms (Figure 1). There was not any relationship between the sizes of the lesions and the ages of the patients. The consistency of the nodules were vary on palpation, amoung them 11 patients (64.7%) had stone-hard nodules.
Calsified masses in the dermis must be seen for the diagnosis of scrotal calcinosis (Figure 2). Amorphous basophilic deposits of calcium were seen as ranging from isolated large dermal lesion to multiple small deposits scattered in the dermis (Figure 3). A foreign body reaction to the calcium and ceratine was found in all of the patients (100%), and additionally 14 of the patients (82.3%) show the presence of histiocytic giant cell (Figure 4a and 4b). Fifteen patients (88.2%) had a true cyst wall composed of stratified squamous epithelium around calcium deposits. It surrounded the calcium deposits completely in nine patients (52.9%) and partially in six patients (35.2%) (Figure 5). Epithelial cysts of varying shapes and sizes were observed in nine patients (52.9%), both normal and inflamed (Figure 6). Mild inflammatory response was seen in five patients (29.4%) and mild acanthosis and hyperkeratosis was seen in six patients (35.2%) overlying the calcifium deposits. The histological features of the patients are listed in Table 1.
The biochemical parameters were observed in the normal range with mean serum phosphorus of 2.9 mg/dl, mean serum calcium of 6.3 mg/dl, and mean serum alkaline phosphatase of 6.2 KAU/100 ml.
Scrotal calcinosis was first described in 1888 by Hutchinson and given the name "idiopathic scrotal calcinosis" by Shapiro et al.( 2) Since then, more then a hundred cases have been reported, but the pathogenic mechanism of the disease is still unclear. Whether the calcified nodules are idiopathic or whether they are due to dystrophic calcification of epidermal or eccrine cysts is the principal debate concerning the cause of this entity (9, 10). Histologic evaluation is mandatory for diagnosing SC and distinguishing it from steatocystoma, actinic keratosis, and other benign tumors, such as lipoma, fibroma, angiokeratoma, and lymphangioma circumscriptum. We reviewed the literature to understand how other pathologists commented the histology of SC. In the literature, scrotal calcinosis has rarely been reported and there is an ongoing debate about the pathogenesis of this rare condition. Unfortunately, SC has usually been described in the form of case reports, with just four original articles reported to date (Table 2). The present study of 17 patients with scrotal calcinosis during a period of 7 years is one of the largest studies of this entity.
The discussion focuses on the role of epidermal cysts in the pathogenesis of SC. A patient, who had 51 nodules, with SC was reported by Song et al. (1). They claimed that firstly epidermal cysts were affected by mild to moderate inflammation, than resorption of cyst walls and keratinous material until the calcified deposits remained. As a result, histopathological findings change depending on the age of cysts and this causes longterm
cysts to have fewer or no epithelial lining cells. On the other hand, King et al. stress the possible role of dystrophic calcification of the dartoic muscle in the genesis of SC (5). Even no evidence of cystic structure was found around calcified material during J. Hicheri's research (11).
Veress at al (12) reported six cases postulating the hypothesis of a special type of dystrophic calcinosis due to minor pressure or trauma and their hypothesis was supported by Malcolm and Feinstein et al.(6, 13). Feinstein et al. described a patient who worked as a farmer and was continuously on a tractor, had calcinosis and vitiligo of the scrotum, this patient made them to believe to the role of repetitive trauma (6). However, a history of repetitive trauma could not be found in any of our patients.
Supporting the Song, several authors identified epithelial cysts in the scrotal skin which showing calcium deposits and they claim that calcinosis of the scrotum is caused by ruptured epithelial cysts (3). Swinehart and Golitz reported three patients, in whom scrotal epidermoid cysts coexisted with scrotal calcinosis, suggesting that scrotal calcinosis may represent the end stage of dystrophic calcification associated with the inflammation of scrotal epidermoid cysts (3). Besides, Bhawan et al. described a granulomatous foreign body reaction around keratinous material in a patient originally described as a case of idiopathic calcinosis of the scrotum (14,15). Similar with the present study, several case series were published for further detection about squamous lining around the dermal calcium deposits and the theory of dystrophic calcification of scrotal epidermoid cysts was also supported by the findings of Soldre et al. (16-18).
The lesions are silent and the main reason patient seek intervention is because of cosmetic concern. Some of the patients need surgical intervention because of intense pruritus or ulceration(19). By the way, it must be keep in mind that scrotal calcinosis can be confused with other lesions. Testicular tumours such as teratomas, gonadoblastomas, and Leydig cell tumours may show calcification or ossification (20). Scrotal calculi are also found in a secondary hydrocele, thus rendering them impalpable. Haematoma and sperm granulomas may produce a solitary echogenic area within the epididymis. The appendix epididymis and appendix testis may calcify and these are recognized by their characteristic position and shape. These lesions are related to previous inflammatory diseases of the epididymis (21).
It is recommended that surgical excision should be limited to the scrotal skin since calcified nodules are localized within the dermis (22). However, extensive disease involving the whole scrotum or florid recurrent disease will require complex scrotal reconstruction. Reconstruction of the scrotal skin is difficult because it has unique functional features. Ruggal nature and thinness of the testicular covering is important for temperature control and optimal spermatogenesis. Mesh skin graft provide a thin covering and a design similar to ruggal skin. Skin flap from the groin or medial circumflex femoral perforator flap can provide thin and mobile cover for scrotal reconstruction. Demir and coworkers using Johnsen score for spermatogenesis found that use of graft in animal for scrotal reconstruction diminishes testicular function whereas use of flaps resulted in testicular function similar to control group (23). More human study needs to be carried out on the best option for scrotal reconstruction.
In the present study, a histopathological spectrum was also observed, which ranges from intact epithelial cysts (88.2%) - inflamed cysts containing calcific material in the lumen but with intact cyst wall (52.9%); calcified inflamed cysts with partial epithelial lining (35.2%); to calcium deposits lying in the dermis (100%), sometimes compressing surrounding collagen fibres to form a pseudocyst (47.1%). The possibility of being 'naked' for larger calcific masses is also significant because excision of the nodule is generally performed in the late, stage even when only the calcified masses remain.
This spectrum of changes in the histology, coupled with the normal values in the biochemical profile, shore up the theory of dystrophic calcification of epithelial cysts. During the time these cysts firstly become inflamed than rupture and finally calcium depocytes replase with the cysts.