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Epidermal inclusion cyst embedded in benign fibrous histiocytic lesion with prominent epithelioid morphology

 Department of Pathology, Deen Dayal Upadhyay Hospital, New Delhi, India

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Date of Submission29-Jul-2021
Date of Decision12-Jan-2022
Date of Acceptance22-Feb-2022
Date of Web Publication26-May-2022


Benign fibrous histiocytoma also known as dermatofibroma is one of the common mesenchymal neoplasms. It commonly develops in young adult with female predominance and predilection for the extremities, particularly lower extremities. Implantation of epidermis in the dermis or subcutaneous tissues may lead to the formation of epidermal inclusion cyst, which is the most common type of epithelial cyst. Development of epidermal inclusion cyst within a benign fibrous histiocytoma is a rare occurrence. This is a unique case of two unrelated lesions.

Keywords: ALK gene fusion, benign fibrous histiocytoma, dermatofibroma, epidermal cyst, epithelioid fibrous histiocytoma

How to cite this URL:
Sood N, Juneja B. Epidermal inclusion cyst embedded in benign fibrous histiocytic lesion with prominent epithelioid morphology. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Dec 1]. Available from:

   Introduction Top

Benign fibrous histiocytoma accounts for approximately 3% of the skin lesion specimens.[1] Some of the histologic variants are fibrocollagenous, cellular, histiocytic, lipidized, angiomatous, aneurysmal, clear cell, monster cell, myxoid, keloidal, palisading, osteoclastic, and epithelioid dermatofibroma.[1],[2] To avoid misdiagnosis from possibly aggressive lesion, correct identification of these variants is important. It is often associated with epithelial hyperplasia. The characteristic epithelial changes are likely to be mesenchyma-mediated and probably represent a host reparative response otherwise known as the inductive phenomenon.[3] Epidermal inclusion cysts are lined by stratified squamous epithelium that is identical to that seen in the normal interfollicular or infundibular epidermis. These cysts may arise from the implantation of the epidermis in the dermis or subcutaneous tissues.[4] The case is a rare incidence of the two unrelated conditions occurring together in one lesion possibly attributed to sequestration of epidermis while healing of burn scar.

Case presentation: A 26-year-old female presented to surgery OPD for swelling on posterior aspect of the right calf for 5 years. It was of size 4 × 3 cm, slow-growing, firm, nontender, nonmobile nodule. Past history revealed a history of burn 1 year back. Computed tomography scan suggested a vascular lesion. The lesion was excised and gross examination showed skin covered exophytic lesion measuring 4 × 3 cm with cystic area found at deeper area and peripherally [Figure 1] and [Figure 1]b. Histopathological sections showed lesion limited to dermis well-circumscribed nonencapsulated tissue with solid and cystic areas and locally infiltrative margins. Epidermis was thickened and showed collarette formation with the underlying dermis separated by narrow grenz zone. Dermis showed proliferation of spindle cell with elongated nuclei. Epithelioid morphology with plump vesicular nuclei, indistinct nucleoli, and abundant cytoplasm was seen in <50% area. Thin intervening collagen and rich vascular network were seen in epithelioid predominant area. Peripheral areas showed thick ectatic blood vessels and lymphoid infiltrate and entrapped thick collagen bundles. Mitosis was infrequent. Focal collection of foamy histiocytes was also present. The cyst at the periphery and deeper end of lesion was lined by stratified squamous epithelium with a granular layer and laminated keratin in the lumen. Cyst wall did not contain eccrine glands, sebaceous glands, or hair follicles. Morphology was suggestive of benign fibrohistiocytic lesion with epithelioid morphology and embedded benign epidermal inclusion cyst. Immunohistochemical staining for CD68 showed strong expression in foamy histiocytic cells. Tumor did not show ALK expression, thus ruling out epithelioid fibrous histiocytoma. CK34-β delineated the epidermal inclusion cyst [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d, [Figure 2]e. On follow-up after 1 year, the patient was well with no sign of recurrence.
Figure 1: (a) MRI scan showing a soft tissue lesion with peripheral cystic area. (b) Gross photograph showing lesion with (4 × 3 cm) grey-white solid cut surface and a large cyst towards periphery

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Figure 2: Microphotograph showing (a) skin covered lesion with narrow grenz zone and cyst lined by squamous epithelium showing expression of the CK 34 Beta (inset). (b) Periphery showing dilated thick-walled ectatic blood vessel. (c) Entrapped collagen and lymphoid infiltrate. (d) Prominent epithelioid morphology with rich vascular network. (e) CD 68 positive histiocytes

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   Discussion Top

Dermatofibroma is a benign, cutaneous, soft tissue tumor accounting for 3% of all the skin lesion specimens of a dermatopathology laboratory.[5] The commonly affected sites by this tumor are lower and upper limbs as skin colored solitary elevated nodule. Other uncommon sites involved are orbit, retroperitoneum, pelvis, knee, head, and neck.[6] There are several histologic variants of cutaneous fibrous histiocytoma; some of them have distinct clinical features such as propensity for local recurrence. The differential diagnosis includes neurofibroma, leiomyosarcoma, and dermatofibroma, atypical benign fibrous histiocytoma.[7] Epithelioid fibrous histiocytoma (EFH) is a rare lesion, which arises from dermal microvascular unit fibroblasts and dendritic histiocytes, commonly affecting fifth decade of life with predominantly male population.[8] EFH with prominent epithelioid morphology was considered as a morphologic variant of benign fibrous histiocytoma because it mimics both vascular and melanocytic neoplasms. ECH is a vascular fibrous histiocytoma. The constituent cells appear to arise from the activation of resident microvascular CD34+ dermal fibroblasts and the accumulation of FXIIIa+ dendritic stromal assembly histiocytes. The CD34+ cells appear to differentiate toward collagenous fibrocytes in association with histiocytes and mast cells in forming collagenous stroma and vessels. ECH is a tumor composed of all requisite cell types consistent with the origin from the dermal microvascular unit. Epithelioid cell histiocytoma (ECH) is composed of all requisite cell types consistent with the origin from the dermal microvascular unit.[9] The molecular basis for the relationship between benign fibrous histiocytoma and epithelioid fibrous histiocytoma has largely remained unknown. Some authors have suggested that an entity EFH is biologically distinct from benign fibrous histiocytoma. Recently, molecular studies have been conducted and pointed out the presence of recurrent anaplastic lymphoma kinase (ALK) gene rearrangements, a phenomenon that is not described in benign fibrous histiocytoma. Next-generation sequencing recently identified VCL and SQSTM1 as distinct ALK fusion partners.[10],[11] Histologically, EFH is composed of plump epithelioid cells (more than 50%) with the other spindle cell component, with focal areas of storiform pattern and variable differentiation toward xanthomatous histiocytic cells. Rich vascular elements with ectatic thick wall are also described as seen in our case. The nuclei are round to ovoid, with vesicular chromatin, minimal or no atypia and scattered bi- and tri-nucleation or multinucleation. In benign fibrous histiocytoma, epithelioid cell morphology should not be more than 50% and EFH lacks lateral collagen entrapment and prominent infiltrate of foamy histiocytes and lymphocytes as seen in BFH. Classic patterns are storiform, pinwheel, or curlicue pattern. Giant cells are rare and mitotic activity is typically scant. These clusters of histiocytic cells show positivity for CD68. Often, it is associated with epithelial hyperplasia. The epithelial changes occur by phenomenon known as inductive phenomenon in which epithelial hyperplasia is mesenchymal mediated and represents host reparative response.[3] In response to injury with tissue repair, these epidermal mesenchymal cellular interactions occur, which is mediated by direct apposition of cells or by epidermal growth factor which is a soluble protein hormone. The epidermal growth factor is produced directly by either autocrine effect or paracrine effect. Epidermoid cysts develop within the infundibulum and can arise anywhere including neck, chest or back, scalp, legs, arms, fingers, genitalia, scrotum, and within the buccal mucosa.[12] Common synonyms include epidermal inclusion cyst, epidermal cyst, and infundibular cyst. The epidermal cyst can be primary or secondary. The cysts arising directly from the infundibulum of the hair follicle are the primary epidermal cysts, which are formed due to plugging of the follicular orifice. Often, these cysts communicate with the skin surface through a small orifice or visible central punctum. The cysts that arise after the implantation of the follicular epithelium in the dermis due to trauma or comedones formation lead to the formation of secondary epidermoid cysts. These cysts are typically nodular and can occur anywhere on the body with a visible central punctum. Histologically, these cysts are lined by stratified squamous epithelium with a granular layer and lumen filled with anucleate keratin flakes. Foreign body giant cell reaction may be seen if cyst ruptures. It is necessary that the surgical resection specimen has wide margins for good prognosis. Local recurrence may occur if simple enucleation of the tumor from the surrounding tissue is done.[13] The presented case is a rare development of epidermal inclusion cyst within the benign fibrous histiocytoma with epithelioid morphology. Fibrous histiocytic lesions with vascular proliferation can be misdiagnosed as vascular tumors on radiology.[14]

   Conclusion Top

Large cystic areas within a fibrous histiocytic lesion need a thorough evaluation. The role of immunohistochemistry in the diagnosis of two coexistent lesions is being highlighted. ALK gene rearrangement study is mandatory to rule out epithelioid fibrous histiocytoma.

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   References Top

Han TY, Chang HS, Lee JH, Lee WM, Son SJ. A Clinical and histopathological study of 122 cases of dermatofibroma (benign fibrous histiocytoma). Ann Dermatol 2011;23:185-92.  Back to cited text no. 1
Canelas MM, Cardoso JC, Andrade PF, Reis JP, Tellechea O. Fibrous histiocytomas: Histopathologic review of 95 cases. An Bras Dermatol 2010;85:211-5.  Back to cited text no. 2
Cao PF, Xu YB, Tang JM, Yang RH, Liu XS. HOXA9 regulates angiogenesis in human hypertrophic scars: Induction of VEGF secretion by epidermal stem cells. Int J Clin Exp Pathol 2014;7:2998-3007.  Back to cited text no. 3
Makhija M. Epidermal inclusion cyst embedded in a recurrent benign fibrous histiocytoma. Indian J Dermatol 2014;59:490-1.  Back to cited text no. 4
[PUBMED]  [Full text]  
Alves JV, Matos DM, Barreiros HF, Bártolo EA. Variants of dermatofibroma--A histopathological study. An Bras Dermatol 2014;89:472-7.  Back to cited text no. 5
Mocellin S. Epithelioid fibrous histiocytoma. In: Soft Tissue Tumors. Switzerland AG: Springer, Cham.; 2021.  Back to cited text no. 6
Prasanna KD, Umesh, Rathi T, Jain V. Benign fibrous histiocytoma: A rare case report and literature review. J Maxillofac Oral Surg 2016;15:116-20.  Back to cited text no. 7
Felty CC, Linos K. Epithelioid fibrous histiocytoma: A concise review. Am J Dermatopathol 2019;41:879-83.  Back to cited text no. 8
Silverman JS, Glusac EJ. Epithelioid cell histiocytoma–histogenetic and kinetics analysis of dermal microvascular unit dendritic cell subpopulations. J Cutan Pathol 2003;30:415-22.  Back to cited text no. 9
Kazakov DV, Kyrpychova L, Martinek P, Grossmann P, Steiner P, Vanecek T, et al. ALK gene fusions in epithelioid fibrous histiocytoma: A study of 14 cases, with new histopathological findings. Am J Dermatopathol 2018;40:805-14.  Back to cited text no. 10
Dickson BC, Swanson D, Charames GS, Fletcher CD, Hornick JL. Epithelioid fibrous histiocytoma: Molecular characterization of ALK fusion partners in 23 cases. Modern Pathol 2018;31:753-62.  Back to cited text no. 11
Zito PM, Scharf R. Epidermoid cyst. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2020.  Back to cited text no. 12
Yamada H, Ishii H, Kondoh T, Seto K. A case of benign fibrous histiocytoma of the upper lip in a 6-month-old infant. J Oral Maxillofac Surg 2002;60:451-4.  Back to cited text no. 13
Saito K, Kobayashi E, Yoshida A, Araki Y, Kubota D, Tanzawa Y, et al. Angiomatoid fibrous histiocytoma: A series of seven cases including genetically confirmed aggressive cases and a literature review. BMC Musculoskelet Disord 2017;18:1-8.  Back to cited text no. 14

Correspondence Address:
Binjul Juneja,
BE-244, Street No.-5, Hari Nagar, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_775_21


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