Tumoral calcinosis (TC) is a rare, benign condition characterized by deposits of calcific material in periarticular soft tissues ^[1]. It most commonly involves the larger joints such as the hip and shoulder, but also has been reported in joints such as the elbow, wrist, knee, scalp, larynx, spine, and sacrum ^[2]. This condition mostly occurs in adolescents and young adults, but familial forms affecting the infants are also described ^[3]. These lesions are slowly growing and progress over the years and may be associated with ulcerations of the overlying skin ^[4]. In 1899, Duret reported two such cases in two siblings and named it as endothelium calcifie ^[5]. In 1935, Teutschlander labeled it as lipocalcino granulomatosis or Teutschlender disease. In 1943, the name was revised to TC by Inclan et al. ^[6]. The etiology of TC is inconclusive despite the proposal of many theories ^[4]. On the basis of underlying etiology, the disease can be primary or secondary to other conditions. Depending upon the phosphate level, primary TC can be normophosphatemic or hyperphosphatemic. The secondary TC is usually secondary to conditions such as chronic kidney diseases, hyperparathyroidism, and hypervitaminosis D ^[7]. In this article, we report a primary recurrent normophosphatemic familial variety of TC in a female patient.

A 63-year-old female patient with no comorbidities presented to our department with a history of progressive swelling over the left upper thigh with discharge of whitish chalky material from the ulceration over it (Fig. 1a).

She was aware of the mass for the last 6 months, associated with minimal dull aching pain following strenuous exertion. She had similar episodes twice in the past, for which she was operated on the first time when she was 16 years old and for the second time around 7 years ago. Among her family members, only one of her younger sisters has a similar mass over the left gluteus region. On examination, an irregular, hard, mildly tender, mobile mass of size 10 × 5 cm was present over the left lateral aspect of the proximal thigh associated with hyperpigmentation of the overlying skin with two linear scar marks. A single ulcer was present at the center of the mass with chalky white fluid discharge (Fig. 1b).

The range of motions of the ipsilateral hip joint was normal, and the local draining lymph nodes were not enlarged. Radiograph revealed an irregular, calcified mass of size 10 × 5 cm over left upper thigh without any involvement of hip joint and proximal femur (Fig. 2a).

Contrast-enhanced computed tomography (CT) of the pelvis revealed an ill-defined, multilobulated amorphous and heterogenous calcified lesion in the subcutaneous plane in the left gluteal region into the left gluteus maximus with minimal involvement of gluteus medius measuring 7.1 × 7.5 × 8.9 cm (Fig. 2b). The coronal CT scan (Bone window and soft tissue window) shows left periarticular multilocular calcified mass with few fluid calcium level suggestive of sedimentation sign (Fig. 2c and d).

On post-contrast images, mild enhancement was seen in the non-calcified soft tissue, and there was no involvement of the bony structure. Magnetic resonance imaging (MRI) revealed a subcutaneous lobulated mass over the left greater trochanteric region of the femur, posterolaterally with fixity to the underlying deep fascia and gluteus maximus. Overlying skin showed focal thickening and scar formation (Fig. 3a, b, c).

Laboratory investigations showed normal phosphate value, without any hematologic value alterations of 1,25-dihydroxyvitamin D or parathyroid hormone. Renal function was normal. Histological examination of the discharge taken from the sinus showed a fibrous connective tissue with amorphous calcified material boarded by a florid proliferation of macrophages and multinucleated osteoclast-like giant cells (Fig. 1c).

Dental examination revealed no abnormality, whereas ophthalmological examination revealed best corrected visual acuity of 6/18 in both eyes and intraocular pressure of 17 mmHg in both eyes. Slit lamp examinations of the anterior segment detected perilimbal calcific deposits (Fig. 4). Ocular fundus examination of the left eye shows an Angioid streak between the disc and macula, multiple pigment epithelial defects, and a choroidal neovascular membrane (CNVM) in the macular area with multiple calcific deposits in the periphery (Fig. 5b). The right eye showed pigment epithelial detachments with multiple calcific deposits in the periphery (Fig. 5a). Optical coherence tomography showed multiple pigmented epithelial defects and CNVMs in both eyes (Fig. 5c). Factoring in the patient history, clinical assessment, and diagnostic evaluation, the final diagnosis of recurrent familial normophosphatemic TC of the greater-trochanteric region was made and planned for wide excision. Patient underwent a wide excision, keeping a 1 cm healthy margin. The resected mass was measured to be 15 cm in the largest diameter, whitish in color, and milky fluid came out during sectioning (Fig. 6a). Pathologic evaluation revealed deeply basophilic amorphous granular material consistent with calcium deposits surrounded by dense fibrous tissue, confirming the diagnosis of TC (Fig. 6b). No cellular atypia and other signs of malignancy were found. The patient was evaluated after 6 months post-discharge. The scar was healthy, and there was no sign of recurrence.

Based on the underlying etiology, Smack et al. ^[7] divided TC into primary or secondary to other conditions. In primary normophosphatemic types, both serum calcium and phosphorus levels are the same without any other hematological abnormalities. It usually presents before the 2^nd decade of life, and this variant is familial, involving the gene encoding the SAMD9 protein ^[7]. In our reported case, repeated hematological investigation showed normophosphatemia, and the patient presented her first episode in the 2^nd decade, for which she had undergone surgery somewhere else. Familial form is also confirmed, as one of her sisters is also affected with a similar presentation. The second group is the primary hyperphosphatemic type, usually presenting during the first and second decades of life. This group of patients has a genetic predisposition with reduced urinary phosphate excretion caused by autosomal recessive mutations in GALNT3 and KLOTHO that cause inactivation of FGF23, a phosphaturic hormone. The third group encompasses secondary TC connected with chronic renal failure, primary hyperparathyroidism, hypervitaminosis D, sarcoidosis, etc. ^[7]. Despite its different etiopathogenesis, the clinical and histopathological features are almost similar to those of our reported case. Joints most commonly affected include the hip, elbow, shoulder, foot, and wrist ^[4,8]. Apart from this, small joints of the hand, such as proximal and distal interphalangeal joints, are also involved ^[9]. These lesions are slow-growing and progress over the years. Lesions may be associated with ulceration of the overlying skin with characteristic chalky white liquid discharge material ^[10]. In children, bone marrow sclerosis and periosteal reactions have also been reported, suggesting its association with chronic recurrent multifocal osteomyelitis ^[3]. Ophthalmological findings include scleral calcification, limbal calcific deposits, angioid streaks, and subretinal neovascular membrane ^[11,12]. Angioid streak in the retina may be related to GALNT3 or FGF23 gene mutation ^[13]. However, we also noted a similar finding, although the above case represents familial normophosphatemic TC. In some cases, calcific deposits in the eyelid and conjunctiva are also seen. There are also possibilities of dental involvement in the form of pulp cavity calcification ^[14]. Preoperatively, TC is diagnosed by various radiological techniques. Findings of amorphous, multiloculated, and cystic calcifications in a periarticular location on plain radiographs are suggestive of TC ^[8]. This well-circumscribed, multilobular radiological appearance is described as a cobblestone or chicken wire appearance. CT serves as a guide for surgical excision. It detects the periarticular calcified mass with sedimentation sign (cystic loculi with fluid levels caused by calcium layering) ^[15]. In MRI, the lesion usually has non-homogeneous diffuse low signal intensity in T1-weighted sequences and alternating signal patterns on T2-weighted images with low signal intensity and cystic components with fluid levels (MRI sedimentation sign) ^[15]. Complete surgical excision has been classically described for the primary type, although it is associated with high recurrence, failure of complete excision, persistence of etiology, high complication rate, and secondary infection ^[16]. Even wider surgical excision, keeping an adequate healthy margin, has also not been proven to prevent recurrence ^[17]. Recurrence is managed by repeated excision. In hyperphosphatemic variants, in order to prevent recurrence, medical managements such as dietary phosphate restriction, use of phosphate binders, acetazolamide, etc., are added postoperatively ^[18].

TC is a rare diagnosis with poorly defined etiologies. We report an unusual recurrence with a metabolically active lesion in an adult female of familial variety following a long period of quiescence. Considering the rarity of the case, difficulty in diagnosis, and ophthalmological findings, the present case has been reported. Clinical features, careful evaluation of imaging findings, and biochemical profile help in reaching the diagnosis. Biopsy is rarely indicated, only in suspicion of malignancy. Wide surgical excision with or without medical treatment can prevent recurrence.

Although TC is a rare entity, a high index of suspicion is needed to rule it out in patients presenting with periarticular calcific deposits. Once a diagnosis is made, all patients should be screened for possible ophthalmological involvement.