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Clinico-cytomorphological spectrum of calcinosis cutis

 Department of Pathology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, Delhi, India

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Date of Submission13-May-2022
Date of Decision13-Jan-2023
Date of Acceptance30-Jan-2023
Date of Web Publication13-Mar-2023


Introduction: The deposition of calcium in the skin is known as calcinosis cutis. It can affect any part of the body and can mimic soft tissue or bony lesions clinically. Aim: To describe the clinical and cytomorphologic features of calcinosis cutis on fine needle aspiration cytology smears. Materials and Methods: A total of 17 cases reported as calcinosis cutis on fine needle aspiration cytology were reviewed for the available clinical and cytological details. Results: The cohort included both adult and pediatric patients. Clinically, the lesions appeared as painless swellings of variable sizes. The common sites affected were the scrotum, iliac region, scalp, pinna, neck, axilla, elbow, arm, thigh, and gluteal region. Aspirate was chalky white, paste-like in all the cases. The cytologic evaluation revealed amorphous crystalline deposits of calcium along with histiocytes, lymphocytes, and multinucleated giant cells. Conclusions: Calcinosis cutis has a wide spectrum of clinical presentations. Fine needle aspiration cytology is a minimally invasive approach for diagnosing calcinosis cutis, thus eliminating the need for more extensive biopsy procedures.

Keywords: Amorphous, calcinosis cutis, calcium, crystalline

How to cite this URL:
Shastri M, Gautam P, Diwaker P, Gogoi P, Arora VK. Clinico-cytomorphological spectrum of calcinosis cutis. J Cytol [Epub ahead of print] [cited 2023 Mar 27]. Available from:

   Introduction Top

Calcinosis cutis is characterized by the accumulation of calcium in the skin and subcutaneous tissue.[1] It may be due to abnormal calcium or phosphorus metabolism, tissue damage, or idiopathic factors.[2] Most cases present as mass lesions. Although it can affect any part of the body, these lesions are frequently seen on proximal extremities, head and neck region, and scrotum.[3]

   Aim Top

To describe the clinical and cytomorphologic spectrum of calcinosis cutis on fine needle aspiration cytology.

   Materials and Methods Top

All cases diagnosed as calcinosis cutis from June 2016 to June 2018 were retrieved from the archives of the Cytopathology section of the Department of Pathology of the institution. A total of 17 cases were found and all these cases were re-evaluated for clinical and cytomorphologic features.

   Results Top

The age of the patients ranged from 10-65 years. Out of 17, 4 patients were ≥60 years of age while 6 patients belonged to pediatric age group (0-19 years). Male to female ratio was found to be 0.8:1. Clinically patients presented with single/multiple, painless, firm to hard, mobile/non-mobile swellings. The size of lesions varied from 1 cm to 6 cm. Scrotum was found to be the most common site of involvement followed by the iliac region [Figure 1]a. Other sites of involvement were the scalp, pinna, neck, axilla, elbow, arm, thigh, and gluteal region [Figure 1]b. The majority of the lesions (14/17) were unilateral. Only one case showed bilateral involvement of the iliac region. The scalp and neck lesions were midline in location. The duration of the lesions varied from 1-10 years. None of the cases had a history of trauma at the site of the lesion. Provisional diagnoses offered by clinicians were epidermal cyst, soft tissue sarcoma, tumor calcinosis, and calcified granuloma. Radiological details (X-ray and MRI) were available in only 2 cases. In 1 case, the MRI report suggested the possibility of soft tissue lesions like extraosseous osteosarcoma or chondrosarcoma, while in another case, X-ray was reported as calcified changes in the absence of bony changes. [Table 1] shows the clinical-cytomorphologic profile of all cases diagnosed as calcinosis cutis.
Figure 1: (a) Nodule on arm (b) hard nodular lesion in iliac region

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Table 1: Clinico-cytomorphologic profile of calcinosis cutis cases (n=17)

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Fine needle aspiration of the lesions was done in all the cases. There was a gritty sensation while needling and chalky white paste-like material was aspirated with difficulty. In a few cases, the needle got blocked by the thick material and no material was aspirated. In these cases, the smears were prepared from the thick chalky white material that oozed out from the FNA site by pressing around the lesion. May-Grunwald Giemsa (MGG) and Papanicolaou (Pap) stains were used to stain the air-dried and alcohol-fixed smears respectively. On cytology smears, the appearance of calcium deposits varied from amorphous intense blue to crystalline deposits which were further highlighted by the Von Kossa stain [Figure 2] and [Figure 3]. The cellular component varied from negligible to the presence of a variable number of histiocytes, lymphocytes, and multinucleated giant cells (MNGCs) [Figure 4]. Based upon the presence of predominantly calcium deposits with or without histiocytes, lymphocytes, and multinucleated giant cells the cases were diagnosed as calcinosis cutis. Histopathological correlation was available in 6/17 cases; the sections showed globular deposits of basophilic calcified material [Figure 3].
Figure 2: Photomicrograph showing crystalline calcium with amorphous granular background (a: MGG, 400x; b: Pap, 400x)

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Figure 3: Photomicrograph showing crystalline calcium deposits on cytology smears (a: Pap, 1000x; b: Von Kossa, 1000x) and globular calcium deposits within dermis in histopathology section (c: H and E, 400x)

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Figure 4: Photomicrograph showing multinucleated giant cell (a: Pap, 400x) and histiocytic cluster (b: MGG, 400x) with abundant amorphous and crystalline calcium

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   Discussion Top

Calcinosis cutis was first described by Virchow in 1855.[1] It is usually seen in the middle to elderly age group and rarely in neonates.[4] Although there is no gender predilection for calcinosis cutis, our case series had more female than male patients. Calcinosis cutis is commonly classified as dystrophic, metastatic, iatrogenic, and idiopathic. Dystrophic is the commonest while idiopathic is the rarest form of calcinosis cutis.[2] Dystrophic calcinosis refers to conditions where calcification occurs in the damaged tissue. These include connective tissue disorders, infections, inflammatory conditions, prolonged venous stasis, cutaneous neoplasms, and trauma. Metastatic calcification refers to the deposition of calcium due to raised amounts of calcium or phosphorus in serum. It is seen in association with renal failure.[5] Iatrogenic calcinosis occurs as a complication of medical procedures like a subcutaneous injection of calcium-containing heparins, extravasation of calcium gluconate, and use of calcium-containing electrode compounds for electromyographic or electroencephalographic examination.[6]

Occupational exposures leading to tissue damage as well as local elevation of calcium concentration have also been implicated as iatrogenic causes of calcinosis cutis. Idiopathic forms like idiopathic scrotal calcinosis and subepidermal calcified nodule are forms of cutaneous calcification of unknown etiology with normal serum calcium.[5],[7] Tumoral calcinosis is a rare clinicopathological entity classified under the idiopathic category.

A negative history of trauma, parenteral therapy, or preceding pathological lesion at the site, along with normal serum calcium and phosphorus levels rule out the possibility of dystrophic, iatrogenic, and metastatic causes of calcinosis cutis. It is termed idiopathic in the absence of any identifiable cause.[5] Calcification can also be seen in the walls of small vessels of the dermis and subcutaneous fat, leading to infarction. This has recently been updated as a fifth category of calcinosis cutis and termed calciphylaxis.[8]

The lesions of calcinosis cutis usually present as painless nodules or swellings anywhere on the body. Extremities and buttocks are the most frequently involved sites. Scrotal involvement by calcinosis cutis is quite commonly seen amongst males and was found to be the most common site in the present series. In childhood, lesions are usually found on the face.[9] Contrary to this, in the present series only one patient in the pediatric age group had a lesion on the face. Lesions involving the proximal aspect of lower extremities and trunk present mostly as tender violaceous nodules and ulceration.[9] However, all nodules in the present series were non-tender, firm to hard without any evidence of ulceration. All 3 cases with iliac involvement were aged 60 years and above. The lesions in the present series were mostly unilateral. Some mobility was observed in nodules over the thigh and neck.

The location of the lesions can also provide a clue about the underlying condition. Dystrophic calcinosis is marked by the characteristic localization of lesions. Involvement of forearms, elbows, fingers, and knees is seen in systemic sclerosis. Elbows, knees, and sites of previous inflammatory lesions are affected in dermatomyositis. The extremities, buttocks, and periarticular areas are frequently involved in lupus erythematosus. Metastatic calcinosis presents with lesions in the periarticular location. The lesions are found around joints in tumoral calcinosis and on the face in children with subepidermal calcified nodules in idiopathic calcinosis. Iatrogenic calcification occurs at sites of venepuncture.[9]

FNA of the lesions in our cases yielded scant to abundant chalky white material which was confirmed on microscopy as calcium. The presence of abundant calcium should prompt inquiry about other differential diagnoses since a thorough microscopic examination of the cytology smears can help in excluding many of them. These differentials include calcified epidermal cyst, calcified fibrous pseudotumor, pilomatricoma, osteitis fibrosa cystica, and extraskeletal osteosarcoma. Sarcoidosis, tuberculosis, and lymphoepithelial lesion are other uncommon differential diagnoses described in the literature.[10]

A calcified epidermal cyst shows anucleate and nucleate squames. A calcified fibrous pseudotumor is marked by the presence of abundant hyalinised collagen, fat, and neurovascular bundles along with calcification.[11] A diagnosis of pilomatricoma is based on the presence of basaloid cells, ghost cells, and multinucleated giant cells in addition to calcification.[12] Calcified tuberculosis and sarcoidosis show the presence of granulomatous reaction while lymphoepithelial lesions have a polymorphous population of lymphoid cells along with histiocytes and calcification.[13],[14] The absence of characteristic malignant cells on microscopy rules out the possibility of extra-skeletal osteosarcoma. Besides cytology, radiology also plays an important role in excluding some of the differentials. Osteitis fibrosa cystica can be diagnosed on the basis of physical examination and radiology.[10]

Thus, FNAC is an easy, non-invasive, and quick method of diagnosing calcinosis cutis and further aids in patient management. While surgical excision followed by histopathological examination is often curative for small calcified deposits and large localized lesions, systemic therapy is required for disseminated and extensive calcinosis.

   Conclusion Top

The wide spectrum of clinical presentation of calcinosis cutis raises the possibility of variable clinical diagnoses, ranging from benign to malignant lesions. Hence, an overview of the diversity of clinical presentation of calcinosis cutis can provide valuable insight into its diagnosis and management protocol. FNAC provides an early, non-invasive approach towards the accurate diagnosis of calcinosis cutis which obviates the need for extensive surgical procedures.

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There are no conflicts of interest.

   References Top

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Correspondence Address:
Preeti Diwaker,
Department of Pathology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, Delhi - 110 095
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/joc.joc_75_22


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1]


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