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  <front>
    <journal-meta id="journal-meta-4659e12cb53a44889384e8eb1b6d9e15">
      <journal-id journal-id-type="nlm-ta">Sciresol</journal-id>
      <journal-id journal-id-type="publisher-id">Sciresol</journal-id>
      <journal-id journal-id-type="journal_submission_guidelines">https://www.jcbsonline.ac.in/</journal-id>
      <journal-title-group>
        <journal-title>Journal of Clinical and Biomedical Sciences</journal-title>
      </journal-title-group>
      <issn publication-format="electronic">2319-2453</issn>
      <issn publication-format="print"/>
    </journal-meta>
    <article-meta id="article-meta-de9224667e144c649ee4587bd5a19eaa">
      <article-id pub-id-type="doi">10.58739/jcbs/v12i4.115</article-id>
      <article-categories>
        <subj-group>
          <subject>Case Report</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title id="article-title-a738601b5b06456da9c214c54258da02">
          <bold id="s-f2317e0cd1a4">Idiopathic Calcinosis Cutis Masquerading as Malignancy - The Mystery of Two Cases Revealed on Cytology</bold>
        </article-title>
        <alt-title alt-title-type="right-running-head">Idiopathic calcinosis cutis masquerading as malignancy</alt-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author" corresp="yes">
          <name id="name-1507cc2a7c7d487f9a91e9e43db8992c">
            <surname>Shilpa</surname>
            <given-names>M D</given-names>
          </name>
          <email>mdshilpa@gmail.com</email>
          <xref id="x-2647c2883bcd" rid="a-1c7052619da7" ref-type="aff">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name id="name-6bac0dcba9b5476090b70e15d9f0e2a9">
            <surname>Harendrakumar</surname>
            <given-names>M L</given-names>
          </name>
          <xref id="x-59e143468097" rid="a-fe7c0513f5f4" ref-type="aff">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name id="name-a4ac27123c104753ad715ed02ef1f488">
            <surname>Dave</surname>
            <given-names>Prakash</given-names>
          </name>
          <xref id="x-49b7aeac245c" rid="a-d1eb231fc8cb" ref-type="aff">3</xref>
        </contrib>
        <aff id="a-1c7052619da7">
          <institution>Associate Professor, Department of Pathology, Sri Devaraj Urs Medical College, Sri Devaraj Urs Academy of  Higher Education and Research</institution>
          <addr-line>Tamaka, Kolar, Karnataka</addr-line>
          <country country="IN">India</country>
        </aff>
        <aff id="a-fe7c0513f5f4">
          <institution>Professor, Department of Pathology, Sri Devaraj Urs Medical College, Sri Devaraj Urs Academy of Higher Education and Research</institution>
          <addr-line>Tamaka, Kolar, Karnataka</addr-line>
          <country country="IN">India</country>
        </aff>
        <aff id="a-d1eb231fc8cb">
          <institution>Professor, Department of Surgery, Sri Devaraj Urs Medical College, Sri Devaraj Urs Academy of Higher Education and Research</institution>
          <addr-line>Tamaka, Kolar, Karnataka</addr-line>
          <country country="IN">India</country>
        </aff>
      </contrib-group>
      <volume>12</volume>
      <issue>4</issue>
      <fpage>147</fpage>
      <permissions>
        <copyright-year>2022</copyright-year>
      </permissions>
      <abstract id="abstract-abstract-title-0813cba6cb2741fa8770b4144c1bbc4c">
        <title id="abstract-title-0813cba6cb2741fa8770b4144c1bbc4c">Abstract</title>
        <p id="paragraph-e866dc2fd20246f0a313fba7b33dfc1e">Calcinosis cutis also commonly called as Calciphylaxis is one of the uncommon conditions characterized by precipitation and deposition of phosphate and calcium salts in the dermis and subcutaneous tissues. We report two different cases clinical diagnosed as malignancy and final diagnosis was made on FNAC which correlated with the histopathology. A 45-year-old women came with a compliant of swelling over lateral aspect of thigh on left side since 6 months. Provisional diagnosis of liposarcoma was made clinically and on FNAC given as Calcinosis cutis which correlated with histopathology. A 62-year-old women came with compliant of swelling over lateral aspect of thigh on right side since 10 months associated with pain. Provisional diagnosis of soft tissue sarcoma was made clinically and advised for FNAC clinically and on FNAC given as Calcinosis cutis which correlated with histopathology. Calcinosis cutis is a condition in which there is organized and localized deposition of calcium in the skin. The evolution of the lesions depends on the aetiology of the calcification. The pathogenesis still remains unclear, but several theories have been suggested for this. Calcinosis cutis is a potential mimic of a neoplastic lesion. FNAC is a simple, rapid and reliable technique and which helps in diagnosis of such lesions.</p>
        <p id="p-6cf1db240910"/>
      </abstract>
      <kwd-group id="kwd-group-e3480b58cbad4f2b93ff6e1b8f3afdf9">
        <title>Keywords</title>
        <kwd>Mimicker</kwd>
        <kwd>Fine needle aspiration cytology</kwd>
        <kwd>Diagnosis</kwd>
      </kwd-group>
      <funding-group>
        <funding-statement>None</funding-statement>
      </funding-group>
    </article-meta>
  </front>
  <body>
    <sec>
      <title id="title-6fa54bf693324b47962afc5ce8d4400b">Introduction</title>
      <p id="paragraph-567f3b527b564b9086e185f9573e92ba">Calcinosis cutis also commonly called as calciphylaxis is one of the uncommon conditions of systemic calcinosis characterized by precipitation and deposition of calcium and phosphate salts in the dermis and subcutaneous tissues. <xref id="xref-3ddd6105cafd47fe9a4539eee40f9112" rid="R164921626829548" ref-type="bibr">1</xref> The pathogenesis is not completely understood. We report two different cases clinical diagnosed as malignancy and final diagnosis was made on FNAC which correlated with the histopathology.</p>
    </sec>
    <sec>
      <title id="title-2b6f12bd428446f4a46d575dc166511c">Case Report 1</title>
      <p id="paragraph-82f339fbda0d4a838227752490f67537">A 45-year-old women came with compliant of swelling over lateral aspect of thigh on left side since 6 months. Initially the swelling was small later gradually increased to the present size of 5X3 cms. It was associated with pain. On examination an irregular swelling of 5X3cms size noted near the lateral anterior superior iliac spine which was hard, tender and non-mobile. Provisional diagnosis of liposarcoma was made clinically and advised for FNAC. The FNAC was performed using 22-gauge needle. On multiple aspirations 2 ml of chalky white material was aspirated. Air dried smears were stained with May Grenwald Giemsa stain and methanol-fixed smears were stained with Hematoxylin &amp; Eosin (H &amp; E) and Pap stain. On microscopy o smears showed flakes of amorphous granular material which stained basophilic on H&amp;E (<xref id="x-7fcd19207380" rid="figure-28f5a8146c78418094026303965dc3b4" ref-type="fig">Figure 1</xref>) and deep blue on Giemsa stain along with few giant cells. Diagnosis was given as Calcinosis cutis. Other investigations like Serum calcium and serum phosphate was done and were within normal limits. Later the lesion was excised and sent for histopathological examination. On histopathological examination it showed large basophilic deposits of calcium within the cystic cavities in the dermis (<xref id="x-f3e956025099" rid="figure-50db6cc7fadb4706b3b694ed08e61bac" ref-type="fig">Figure 2</xref>) with giant cell reaction at places was noted and final diagnosis was given as Calcinosis cutis. </p>
      <fig id="figure-28f5a8146c78418094026303965dc3b4" orientation="portrait" fig-type="graphic" position="anchor">
        <label>Figure 1 </label>
        <caption id="caption-bb6a9940111048b0b5aa4197c80dbbc0">
          <title id="title-8345989b15254e26b89dccb70abf36e6">
            <bold id="strong-be3da97d83d34fe7aaff0a4fcc2c0879">FNAC H&amp;E smear (100X)</bold>
            <bold id="strong-cc59b6baaf4b467a9bf31c175876db53">showing flakes of amorphous material</bold>
          </title>
        </caption>
        <graphic id="graphic-4803649d457a445d8d6ee0b7d9408ada" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/55e15526-a0cf-41ed-b9f9-37b5a435d2deimage1.png"/>
      </fig>
      <fig id="figure-50db6cc7fadb4706b3b694ed08e61bac" orientation="portrait" fig-type="graphic" position="anchor">
        <label>Figure 2 </label>
        <caption id="caption-3de62a9cbcb94f9d893cf110e51f9af6">
          <title id="title-9fd5492ca07b449fa47f71c65919a7a7">
            <bold id="strong-5f5c8146072f4f6a8b73c7d2cc67d7ad">Histopathology H&amp;E section (100X) showing cystic cavities filled with large basophilic deposits</bold>
          </title>
        </caption>
        <graphic id="graphic-1f2f6f3b082b4e18ba8fc9ab3759cf51" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/55e15526-a0cf-41ed-b9f9-37b5a435d2deimage2.png"/>
      </fig>
    </sec>
    <sec>
      <title id="title-3f7e0b940b544338858da8df027d081d">Case Report 2</title>
      <p id="paragraph-fa69f8df6c954d3fa7136ac0cbabe49b">A 62-year-old women came with compliant of swelling over lateral aspect of thigh on right side since 6 months associated with pain. On examination an irregular swelling measuring 8X5cm in size noted near right iliac crest which was hard, tender and non-mobile. Provisional diagnosis of soft tissue sarcoma was made clinically and advised for FNAC. The FNAC was performed using 22-gauge needles. On multiple aspirations 5 ml of chalky white material was aspirated. Air dried smears were stained with May Grenwald Giemsa stain and methanol-fixed smears were stained with Pap stain and Hematoxylin &amp; Eosin (H &amp; E). Microscopy of the smears showed flakes of amorphous granular material that stained on Pap stain (<xref id="x-8f43c72ae349" rid="figure-fcde4ab0a23f47f78030f299877e9891" ref-type="fig">Figure 3</xref>) and deep blue on Giemsa stain along with histiocytes and lymphocytes. Diagnosis was given as Calcinosis cutis. Further biochemical investigations like serum alkaline phosphatase, calcium and phosphorus levels were done and all were in normal limits. Later surgical excision was done and it was sent for histopathological examination. On microscopy large nests of basophilic calcific material separated by fibrous septa in the dermis along with giant cell reaction was noted (<xref id="x-84ec42f71513" rid="figure-9800ea85607b43f48d6283a79adc7429" ref-type="fig">Figure 4</xref>). The overlying epidermis was normal. With these findings final diagnosis of Calcinosis cutis was given.</p>
      <fig id="figure-fcde4ab0a23f47f78030f299877e9891" orientation="portrait" fig-type="graphic" position="anchor">
        <label>Figure 3 </label>
        <caption id="caption-06c53129c40e415ab9ece4b84fb184dc">
          <title id="title-44db7ece73d24938a4ca391b4973f3bc">
            <bold id="strong-e2736e2ee5a74c1499be7d7e3597464d">FNAC Pap smear (400X)</bold>
            <bold id="strong-6472c8a02cfb498787e4a003a79505df">showing</bold>
            <bold id="strong-2198f3bb96404c07bdb422f1ce1ecbf1"> </bold>
            <bold id="strong-b9fbafe5dc704277976006b6fb8b1b53">flakes of amorphous material</bold>
          </title>
        </caption>
        <graphic id="graphic-6a375eb69e4b4dcb80b2866fabfe3ad0" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/55e15526-a0cf-41ed-b9f9-37b5a435d2deimage3.png"/>
      </fig>
      <fig id="figure-9800ea85607b43f48d6283a79adc7429" orientation="portrait" fig-type="graphic" position="anchor">
        <label>Figure 4 </label>
        <caption id="caption-6e42f613007c48b783c8ff06bb55e72c">
          <title id="title-0e8b0a18836b417ab8cc83ac28018bd3">
            <bold id="strong-c7e1acfd2d16471aa5de0402d1cc40ef">Histopathology H&amp;E (400X)</bold>
            <bold id="strong-9533e7f8c4a84b0fa77a77e766629ce2">showing giant cell reaction (arrow)</bold>
          </title>
        </caption>
        <graphic id="graphic-beaf631ce2e642609ca766adab9de3c8" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/55e15526-a0cf-41ed-b9f9-37b5a435d2deimage4.png"/>
      </fig>
    </sec>
    <sec>
      <title id="title-53f453c0739e439a98a1aebae9db6049">Discussion</title>
      <p id="paragraph-5ddfa705f98247e0ab27dc6784fc301d">Calcinosis cutis is a condition with localized and organized deposition of calcium in the skin. It was first described by Rudolf Virchow in 1855. <xref id="xref-23e872c8f69d44c79c3beacc964b7758" rid="R164921626829546" ref-type="bibr">2</xref> It is divided into four major types based on etiology and they are metastatic, dystrophic, idiopathic and iatrogenic. Other rare types are tumoral calcinosis, calcinosis cutis universalis, calcinosis cutis circumscripta and transplant associated calcinosis cutis. <xref id="xref-6c8db8b9bca84c73ad020f3578e96c49" rid="R164921626829547" ref-type="bibr">3</xref> Most lesions are asymptomatic and develop gradually. <xref id="xref-f673e21399134ac395ff1ea3d05c509e" rid="R164921626829552" ref-type="bibr">4</xref></p>
      <p id="paragraph-38aa15d43ec849859c1d5e8fa649cbe2">The sites most commonly affected are the superior and lateral shoulder, posterior elbows, and lateral hip and gluteal regions. Rarely has it been noted in the hands, feet, spine, temporo mandibular joint &amp; knee. <xref id="xref-dea29e40652644c79995decfc2a8901b" rid="R164921626829548" ref-type="bibr">1</xref></p>
      <p id="paragraph-504a77b37f50470c88413b4614f040b3">The development of these lesions depends on the causes for the calcification. The patients with history of chronic renal failure with abnormal serum and phosphate levels usually develop metastatic type Calcinosis. The patients with history of any trauma or an underlying disease with normal serum calcium and phosphate levels most commonly have dystrophic type calcinosis. The patients with iatrogenic calcinosis cutis will generally provide history of recent hospitalization. <xref id="xref-baf895b5b55d4fffbf467f3071c6395f" rid="R164921626829549" ref-type="bibr">5</xref></p>
      <p id="paragraph-634b853bd3544750b3f73abdb6840d16">The cases with idiopathic calcinosis cutis will not associated with any underlying disease, pervious trauma and recent hospitalization like in our both the cases. The pathogenesis of idiopathic calcinosis cutis is still unknown. <xref id="xref-f846033ed234437f9dfc2b769c36370a" rid="R164921626829552" ref-type="bibr">4</xref></p>
      <p id="paragraph-a13bcd08ae5c4394bdc3914571e8cbeb">In all the cases of Calcinosis cutis due to local and systemic factors the insoluble compounds of calcium get deposited. These calcium salts include primarily of amorphous calcium phosphate and hydroxyapatite crystals. The pathogenesis for this is still unknown and several theories have been suggested. Hypercalcemia and hyperphosphatemia have been described as the underlying cause in some patients while local trauma has been implicated in a few cases. <xref id="xref-0376a9c58e124b088c9414773b465cdf" rid="R164921626829547" ref-type="bibr">3</xref></p>
      <p id="paragraph-7dad0374db7143a0a562ffaf6e53707d">In the present both the cases all the investigations to evaluate abnormal calcium metabolism revealed results within normal limits and the diagnosis made was based on the cytomorphological findings and it was confirmed on histopathological examination.</p>
      <p id="paragraph-d60dc7ed760a4a5dab51c8900365e4c1">The sample yield on FNA is chalky white granular material and the following differential diagnosis have to be considered which includes Epidermal cyst with calcification, Sarcoidois, Pilomatricoma, calcified fibrous pseudotumor, tuberculosis, osteitis fibrosa cystica and extra skeletal osteosarcoma. Calcified epidermal cyst shows nucleate and anucleate squames <xref rid="R164921626829550" ref-type="bibr">6</xref>, <xref rid="R164921626829554" ref-type="bibr">7</xref> whereas Sarcoidosis and Calcified tuberculosis show granulomatous reaction. <xref rid="R164921626829550" ref-type="bibr">6</xref>, <xref rid="R164921626829553" ref-type="bibr">8</xref> Pilomatricoma shows mainly ghost cells, basaloid cells and multinucleate giant cells. Abundant hyalinised collagen, fat and neovascular bundles along with calcification are the features of calcified fibrous pseudotumor. <xref rid="R164921626829550" ref-type="bibr">6</xref>, <xref rid="R164921626829551" ref-type="bibr">9</xref> Lymphoepithelial lesions show a polymorphous </p>
      <p id="paragraph-2fb7eca0b92d47b9a026d4f258ee46a9">lymphoid cell population along with histiocytes and calcification. Absence of tumor cells rules out extraskeletal osteosarcoma. The clinical history helps in evaluation of osteitis fibrosa cystica.</p>
      <p id="paragraph-b737807339a74a8581015864662a833c">Anupama et al. studied the cytological features of idiopathic calcinosis cutis of the back and noted dense basophilic amorphous granular material without any evidence of epithelial cells. <xref id="xref-ce07ea029fa44021a21a976038963d1f" rid="R164921626829548" ref-type="bibr">1</xref> In both of our cases there was no history of trauma, any underlying disease, hospitalization, previous parenteral therapy or any preceding pathological lesion at the site. Also normal serum calcium and phosphorus levels clearly excluded the possibility of metastatic, dystrophic and iatrogenic causes and hence a final diagnosis of idiopathic calcinosis cutis was made.</p>
      <p id="paragraph-2810fb4314f1488c840cdcb2848e900d">The treatment for both large, localized lesions and small calcified lesions is surgical excision, and it also allows for further histopathological examination which is required for the confirmation of diagnosis. Whereas for disseminated and extended calcinosis systemic therapy is used. Various treatment modalities have been tried which includes warfarin, bisphosphonates,   minocycline, diltiazem, intralesional steroids, carbon dioxide laser and extracorporeal shock wave lithotripsy and they have been shown to have beneficial effects. <xref id="xref-de5c02853dce42d7846a6d1e2fb53319" rid="R164921626829546" ref-type="bibr">2</xref> In our both the cases surgical excision was the treatment of choice and both the patients were on follow up and doing well.</p>
      <p id="paragraph-78462a29ed8843b385d97942d29811a2">After through literature search only very few case reports have been reported till date on FNA cytology of idiopathic calcinosis cutis. Correct cytomorphological diagnosis helps in determining cases requiring surgical rather than medical treatment.</p>
    </sec>
    <sec>
      <title id="title-d728764cd7c741848359e3b08a0b1221">Conclusion</title>
      <p id="paragraph-e7e667c4f3d04ffabe13ee9062a71113">The present cases are highlighted to alert the pathologists and they should consider Calcinosis cutis as the one of the differential diagnosis in any swelling with a chalky white granular aspirate on FNA technique as it is a potential mimic of a neoplastic lesion. FNAC is a simple, rapid and reliable technique and is of great diagnostic investigation especially in soft tissue lesions like calcinosis cutis. FNA features along with the serological and biochemical findings can help in effective patient management.</p>
    </sec>
  </body>
  <back>
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