Archives of Health Science Complimentary Article

The Enclosed Leviathan- Pleomorphic

Dr Anubha Bajaj* Consultant Histopathologist, A. B. Diagnostics, A-1, Ring Road, Rajouri Garden, New Delhi, India. *Corresponding Author: Dr Anubha Bajaj, Consultant Histopathologist, A. B. Diagnostics, A-1, Ring Road, Rajouri Garden, New Delhi, India. Preface in middle aged to older adults with a peak emergence within the fifth decade of life. A Cutaneous pleomorphic fibroma specific gender predilection is absent (2,4). was initially described by Kamino et al in 1989 as a dermal, pauci-cellular neoplasm Pleomorphic fibroma is associated with an abundant fibrous tissue stroma, with benign biological behaviour in spite of atypical fibro-histiocytic cells and extensive cellular pleomorphism (2). disseminated multinucleated giant cells(1). Of obscure pathogenesis, Pleomorphic fibroma is an exceptional, pleomorphic fibroma is contemplated as a benign, polypoid ordome shaped, sparsely neoplasm of fibroblastic or myofibroblastic cellular, cutaneous fibroblastic neoplasm origin on account of immune reactivity to characteristically delineating aberrant, vimentin and actin along with abundance of pleomorphic, hyperchromatic and giant collagenous stroma. Certain instances are multinucleated cells embedded in a immune reactive to Factor XIIIa and CD34 collagenous stroma (2). Pleomorphic fibroma due to the presence of reactive dermal is contemplated to originate from dendrocytes, a theory favouring a dermal dendrocytes, in contrast to myofibroblasts. dendritic cell origin. Immune non reactivity The exceptional neoplasm can simulate to S100 protein eliminates the possibility of adjunctive fibro-histiocytic, melanocytic or melanocytic or neural tumour genesis (4). lipomatous neoplasia. Despite cellular and nuclear atypia accompanying pleomorphic, Distinct variants are described, bizarre cells, the neoplasm is contemplated as contingent to denomination of predominant architecturally and biologically benign, on intervening stroma, as sclerotic and myxoid account of exceptional or absent mitosis(2). pleomorphic fibroma (4). Pleomorphic fibroma may be interlinked with Cutaneous pleomorphic fibroma is a sclerotic fibroma. Martin-Lopez defined the variant of sclerotic fibroma, thus can be terminology “pleomorphic sclerotic fibroma” designated as pleomorphic sclerotic fibroma. which posits pleomorphic fibroma, sclerotic Myxofibrosarcoma can arise from fibroma and pleomorphic sclerotic fibroma myxoid pleomorphic fibroma. The as neoplasia representing a morphologic metamorphoses can be a true malignant continuum (3). metamorphoses or an incidental alteration Disease Characteristics although the fact remains undecided (4,5). Clinical Elucidation As an exceptional, fibro-histiocytic neoplasm, pleomorphic fibroma commonly Pleomorphic fibroma is arises upon the trunk and proximal predominantly situated within the dermis extremities. Infrequently, the tumefaction and the polypoid, sparsely cellular can arise upon sites such as head and neck, neoplasm is configured with coarse bundles scalp, tendon sheath, subungual space, of collagen. Marked cellular atypia and forehead, retro-auricular area, eyelid or pleomorphism in the absence of mitosis is a nose. Typically, pleomorphic fibroma occurs characteristic feature of the neoplasm.

Archives of Health Science 1 The Enclosed Leviathan- Pleomorphic Fibroma

Concurrent absence of necrosis and mitosis paracrine influence of entangled mast cells demarcates the tumour from malignant can generate the cytological atypia neoplasia (4,5). characteristic of pleomorphic fibroma (5,6). The tumefaction represents as a A well circumscribed, pedunculated superficial, painless, gradually evolving, neoplasm with superimposed stratified enlarged, pedunculated, polypoid, squamous epithelial layer can be delineated. indurated, flesh coloured lesion. Papillary and reticular dermis display a The neoplasm can manifest as a dome hypo-cellular tumefaction with haphazardly shaped papule, nodule or an asymptomatic dispersed, thick collagen bundles neoplasm of variable magnitude, commonly intermixed with partially detached stroma between 4 millimetres to 40 millimetres. and dilated vascular articulations. Tumour The neoplasm can clinically simulate a cells are spindle-shaped or irregular with nevus or neural tumour or or scanty cytoplasm and indistinct cytoplasmic acrochordon with cytological atypia(4,5). outline. Floret- like, giant multinucleated Histological Elucidation cells are intermingled with the cellular component. Cellular nuclei are significantly Grossly, a well circumscribed, solid, atypical, enlarged, pleomorphic and dome shaped nodule with greyish/ white, hyperchromatic. Foci of tumour sclerosis or fibrotic cut surface is denominated. The myxoid foci may be discerned (5,6). tumefaction is variably cellular, resembles a Discernible nuclear atypia simulates fibro-epithelial polyp and denominates degenerative alterations demonstrated in spindle- shaped cells with striking nuclear several benign mesenchymal neoplasms. pleomorphism and atypia. The sparsely Variants of pleomorphic fibroma with a cellular neoplasm is configured of myxoidstroma can be delineated (6). pleomorphic cells admixed with dense, haphazardly scattered collagen bundles. Pleomorphic tumour cells are fusiform with enlarged, hyperchromatic, bizarre and smudged nuclei. Few multinucleated tumour giant cells are observed (5,6). On fine needle aspiration cytology, Figure1. Pleomorphic fibroma enunciating cellular aggregates are intermixed with accumulation of plump, atypical fibroblasts with metachromatic stromal fragments hyperchromatic nuclei and a superimposed comprised of collagen bundles. Pleomorphic stratified squamous epithelium (10). tumours cells are singly dispersed or configure clusters and incorporate enlarged nuclei (monster cells) with scanty cytoplasm or tumour cells may be stripped of cytoplasm. Few nuclei display a singular nucleolus. Nuclear membrane is undulating and frequently depicts notches, creases and Figure2. Pleomorphic fibroma exhibiting folds. Pleomorphic tumour cells are aggregates of plump, atypical fibroblasts admixed with spindle-shaped cells and enveloped in a fibrotic stroma and an absence of multinucleated giant cells. Foci of necrosis mitosis (11). or mitosis are absent or scarce (5,6). A dermal, pauci-cellular neoplasm with an abundant, fibrous tissue stroma is observed which is composed of atypical, fibro-histiocytic cells and few disseminated multinucleated giant cells. Occasional, aberrant mitosis, attributed to degenerative Figure3. Pleomorphic fibroma with dispersed alterations, can be discerned. Mononuclear plump fibroblasts displaying nuclear atypia, cells with atypical nuclear features can hyperchromasia and pleomorphism with a lack concur with multinucleated tumour giant of mitosis, embedded in a collagenous stroma (12). cells. Cellular degeneration, ischemia or

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reactivity to muscle specific actin (MSA) is discerned. Cells are immune non reactive to desmin, S100 protein, cytokeratin, CD10, CD31, α1- anti-chymotrypsin, α1- antitrypsin and Factor XIIIa. Proliferation

index Ki-67 is usually beneath <5%. Figure4. Pleomorphic fibroma depicting Immune reactivity to CD68 and Factor XIIIa dispersed plump fibroblastic cells with nuclear can be absent, moderate or patchy (2,4). atypia and pleomorphism, encompassing fibrous tissue stroma and a superficial lining of Differential Diagnosis stratified squamous epithelium(13). Pleomorphic fibroma necessitates a demarcation from diverse fibro-histiocytic and melanocytic neoplasms demonstrating cellular pleomorphism and significant cellular atypia such as with monster cells (DFMC) and atypical Figure5. Pleomorphic fibroma delineating fibroxanthoma (AFX) (6). aggregates of plump, pleomorphic, fibroblastic (AFX) and cells with nuclear atypia and lack of mitosis, a pleomorphic dermal are circumscription of fibrotic stroma and a superimposed layer of stratified squamous neoplasms which generally exhibit epithelium(14). enhanced cellularity and pleomorphism with frequent mitosis and often demonstrate xanthomatous cells. Atypical fibroxanthoma is a cellular neoplasm with an excess of mitotic figures. Atypical fibroxanthoma manifests as a rapidly progressive lesion of enhanced cellularity. The neoplasm is composed of pleomorphic Figure6. Pleomorphic fibroma demonstrating atypical, pleomorphic fibroblastic cells or spindle- shaped cells along with intermixed within a collagenous stroma and numerous mitotic figures, a few of which absent mitosis(15). may be atypical (6, 7). Anomalous variations of dermatofibroma such as dermatofibroma with atypical or monster cells (DFMC) characteristically demonstrate epithelial hyperplasia, a hyper-cellular stroma along

with foam cells and hemosiderin- laden Figure7. Pleomorphic fibroma on fine needle macrophages. Aforesaid macrophages are aspiration cytology depicting clusters of occasionally immune reactive to CD68 enlarged, pleomorphic cells entangled with although the neoplasm is immune non fibro- stroma(16). reactive to CD34, in contrast to pleomorphic fibroma (6,7). Cytological distinction of cutaneous pleomorphic fibroma is necessitated from atypicalfibroxanthoma, dermatofibroma with monster cells, giant cell fibroblastoma, Figure8. Pleomorphic fibroma immune reactive desmoplastic Spitz nevus and desmoplastic tovimentin (16). melanoma. Pleomorphic fibroma can be Immune Histochemical Elucidation misinterpreted as a malignant soft tissue neoplasm upon fine needle aspiration Tumour cells are diffusely immune reactive cytology on account of constituent bizarre, to vimentin, CD34, actin pleomorphic cells with significant atypia (SMA) and CD68. Occasional immune (7,8).

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The cellular atypical fibrous minute 2homolog (MDM2) within atypical or dermatofibroma with lipomatous tumours can be adopted. The atypical or monster cells (DFMC) is a neoplasm incorporates chromosomal cellular neoplasm with a storiform tumour rearrangement 12q 15(8,9). configuration and displays typical Nevertheless, fluorescent in situ histological foci of dermatofibromaalong hybridization (FISH) is contemplated as a with foam cells and hemosiderin- laden specific, pertinent diagnostic modality (9). macrophages and are immune non reactive Associated adipose tissue neoplasms, to CD34. In contrast, pleomorphic fibroma immune reactive to S100 protein require delineates bundles of collagen and is segregation. Sclerotic , a variant of immune reactive to CD34, thus eliminating lipoma demonstrates adipocytes atypical fibroxanthoma and interspersed within a whorled, fibrotic dermatofibroma with atypical or monster stroma. Dermal pleomorphic is cells (7,8). an exceptional, high grade variant of Giant cell fibroblastoma is a liposarcoma which typically enunciates paediatric neoplasm typically associated pleomorphic lipoblasts(8,9). with localized tumour infiltration and is a benign manifests sinusoidal articulations. entity which simulates pleomorphic Characteristically, pseudo-vascular spaces fibroma with an immune non reactive and layered by aberrant multinucleated cells, absent expression of retinoblastoma1 (Rb1) immune reactive to CD34, are discerned molecule upon fluorescent in situ whereas adult lesions are devoid of invasive hybridization (FISH). Thus, pleomorphic tumour growth and sinusoidal fibroma may be posited as a variant of configurations (8,9). pleomorphic lipoma(8,9). Spitz nevus, desmoplastic Pleomorphic fibroma mandates a melanoma and atypical variants of neural demarcation from soft fibroma, intradermal tumours demonstrate milder cellular nevus, neurofibroma and cutaneous pleomorphism and are immune reactive to appendageal tumours. In contrast to S100 protein (8). aforementioned neoplasms, pleomorphic fibroma demonstrates cellularity with Desmoplastic Spitz nevus and atypical cells, pleomorphic, hyperchromatic desmoplastic melanoma exhibit focal areas nuclei and exceptional mitotic figures (8,9). of melanocytic differentiation wherein tumour cells are immune reactive to S100 Cogent evaluation of clinical protein(8). Benign nerve sheath tumours representation, histological features and with atypical features such as neurofibroma immune reactivity of pleomorphic fibroma with atypical features or schwannoma with is necessitated in order to circumvent ancient change necessitate a demarcation. potential misinterpretation as a benign soft Benign nerve sheath tumours are immune fibroma or skin appendageal tumour or a reactive to S100 protein. Atypical cellular neoplasm with atypical cellular modifications can be degenerative and articulations such as dermatofibroma with probably arise secondary to ischemia (8,9). monster cells (DFMC) or atypical fibroxanthoma (AFX), conditions which can Angiofibroma is a predominantly be therapeutically alleviated with a vascular neoplasm which demonstrates comprehensive surgical extermination(8,9). pleomorphic cells identical to pleomorphic fibroma (8,9). Therapeutic Options Atypical cutaneouslipomatous Comprehensive surgical neoplasm mandates a segregation on extermination of the neoplasm is account of prominent adipose tissue recommended and usually curative. component or in instances where Although uncommon, shave biopsy and pleomorphic fibroma exhibits entrapped electrodessication can be accompanied by adipose tissue cells. Cogent immune localized tumour reoccurrence, a feature reactivity and fluorescent in situ which usually follows incomplete surgical hybridization (FISH) assay to discern extermination of the neoplasm. Extended enhanced expression of mouse double monitoring is necessitated (8,9). Archives of Health Science 4 The Enclosed Leviathan- Pleomorphic Fibroma References [6] Tashakori M, Pimentel J et al” Pleomorphic fibroma of the skin with MDM2 [1] Kamino H, Lee JY et al” Pleomorphic immunoreactivity : a potential diagnostic fibroma of the skin : a benign neoplasm pitfall” J CutanPathol 2018: 45;59-62. with cytologic atypia. A clinicopathologic [7] Al-Zaid T, Wang WL et al” Pleomorphic study of eight cases” Am J SurgPathol fibroma and dermal atypical lipomatous 1989:13;107-13. tumour: are they related?” J CutanPathol [2] Garbayo-Salmons P, Casulleras-Gonzales A 2013:40; 379-84. et al” Giant cutaneous pleomorphic [8] David EE, Rosalie E et al” Lever’s fibroma: an unusual presentation” Clinical Histopathology of skin -11th edition” and Experimental Dermatology 2020: 45; Philadelphia , Wolters Kluwer 2015:1218-9. 97-99. [9] Yadav YK, Khushwaha R et al” [3] Martin-Lopez R, Feal-Cortizas C et al” Cytomorphology of pleomorphic fibroma Pleomorphic fibrotic sarcoma” of skin: a diagnostic enigma” JCytol Dermatology 1999: 198; 69-72. 2013:30(1); 71-73. 10)Image 1 Courtesy: Memorang.com [4] Hinds B, Agullo-Perez AD et al “Loss of retinoblastoma in pleomorphic fibroma: an [10] Image 2 Courtesy: Basic Medical Key immunohistochemical and genomic [11] Image 3 Courtesy: Research Gate analysis” J CutanPathol 2017: 44; 665-71. [12] Image 4 Courtesy: Plastic Surgery Key [5] Chae JK, Noh SH et al “ A case of [13] Image 5 Courtesy: Wikipedia pleomorphic fibroma of the nose”Hong [14] Image 6 Courtesy:Dovemed.com Kong J Dermatol Venereol 2015 :23; 187- [15] Image 7 and 8Courtesy:J Cytol.com 190.

Citation: Dr Anubha Bajaj, (2020), “The Enclosed Leviathan- Pleomorphic Fibroma”, Arch Health Sci; 4(1): 1-5.

DOI: 10.31829/2641-7456/ahs2020-4(1)-115

Copyright: © 2020 Dr Anubha Bajaj, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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