Untitled Quiz | Dermatol Pract Concept 2015;5(4):5 17 DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com The patient An otherwise healthy 34-year-old Brazilian male presented with an asymptomatic, slow-growing lesion on his left malar region for six months. No previous personal or familial similar findings were known. On examination, there was a well-circumscribed, raised, pink, telangiectatic, smooth nod- ule of hard consistency, measuring 1.2 x 1.2 cm in its base (Figure 1A). An excisional biopsy with clear margins was carried out. Additional select histopathologic pictures are depicted (Figures 1B, 2A-G, 3). A quiz from Manaus, Brazil Mario F. Ribeiro de Miranda1, Antonio P. Mendes Schettini2, Laís Cruz Lobato2, Renato C. da Silva Jr2, Patricia Motta de Morais2, Maraya de Jesus Semblano Bittencourt1 1 Department of Dermatology, Universidade Federal do Para, Belem, PA, Brazil 2 Fundação de Dermatologia Tropical e Venereologia Alfredo de Matta, Manaus (AM), Brazil Citation: de Miranda MFR, Schettini APM, Lobato LC, da Silva Jr RC, de Morais PM, Bittencourt MJS. A quiz from Manaus, Brazil. Dermatol Pract Concept 2015;5(4):5. doi: 10.5826/dpc.0504a05 Copyright: ©2015 Miranda et al. 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. Corresponding author: Antonio Pedro Mendes Schettini, MsC, Rua Benjamin Lima, 16, Planalto, Manaus (AM), 69044-040 Brazil. Email: apmschettini@gmail.com Figure 1A. Nodular lesion over a background of acne scars. [Copy- right: ©2015 Miranda et al.] Figure 1B. Hyper- (top) and hypocellular (bottom) areas with clefts. Note atrophic epidermis, Grenz zone and a dilated entrapped follicle (H&E x40). [Copyright: ©2015 Miranda et al.] What is your diagnosis? Answer and explanation Sclerotic fibroma A sharply circumscribed, mostly hypocellular, non-encapsu- lated, spindle cell proliferation, expanded to the deep dermis, along with hyalinized collagen and clefts, arranged in a stori- form/whorled (so-called “plywood”-like) pattern is in concert 18 Quiz | Dermatol Pract Concept 2015;5(4):5 Figure 2A. Stromal clefts and spindle cells in storiform and whorled fashions (H&E x100). [Copyright: ©2015 Miranda et al.] Figure 2B. Hypocellular area with fusiform and stellate-shaped neo- plastic cells in sclerotic collagen (H&E x400). [Copyright: ©2015 Miranda et al.] Figure 2C. Histiocytoid cells with plump nuclei, some showing multinucleation, are seen in the uppermost part of the lesion (H&E x400). [Copyright: ©2015 Miranda et al.] Figure 2D. Sharp demarcation of the lesion from the surrounding dermal tissue (H&E x40). [Copyright: ©2015 Miranda et al.] Figure 2E. Epidermal collarette (H&E x40). [Copyright: ©2015 Mi- randa et al.] Quiz | Dermatol Pract Concept 2015;5(4):5 19 basaloid follicular induction and basal hyperpigmentation. In contrast to DF, SF affects mainly the face, shows an expansile growth pattern and a sharp circumscription, but no acantho- sis or basaloid follicular induction [2]. Besides DF, an invo- lutional sclerotic stage of other pre-existing inflammatory, hamartomatous or neoplastic lesion such as angiofibroma, neurofibroma, melanocytic nevus, lipoma, tendon sheath fibroma (which is never dermal), giant cell collagenoma, erythema elevatum diutinum, solitary myofibroma and chronic folliculitis had been also considered [6,7]. In addi- tion, although some of the above-mentioned SF attributes may be observed in DF, CD34 staining is usually absent in the latter [2,8,9]. Multinucleated and stellate-shaped cells, dilated vessels and collagen bundles oriented around hair follicles are seen in fibrous papules/angiofibromas, but hyalinization and cleft formation are not expected features [10]. As fibrosis was not oriented in parallel to the epidermis in this case, a scar has easily been excluded. Although the hyalinizing process seen in keloids share striking similarities with SF, these sclerosing lesions lacked the “plywood”-like pattern characteristic of SF [11]. Dermatofibrosarcoma protuberans (DFSP) is a malig- nant mesenchymal neoplasm of low metastatic potential. In contrast to SF, it shows infiltration of the subcutis and poor circumscribed margins. Moreover, hyalinized areas are usu- ally absent, and one observes a denser cellularity. Expression of CD34 is used as an ancillary help to the differential diag- nosis of DFSP with other cutaneous spindle cell neoplasms [8]. Giant cell fibroblastoma (GCF) is closely related to DFSP sharing the same cytogenetic abnormality involving genes COLIA1 on chromosome 17 and PDGFB on chromosome 22 [8]. GCF primarily affects children, presenting as a sub- cutaneous mass composed of a hypocellular proliferation of spindle-shaped cells and scattered giant cells with multiple with sclerotic fibroma (SF) [1-3]. Immunohistochemically the neoplastic cells showed diffuse reactivity to CD34 (Figure 3), but negative staining with S-100 protein, desmin, smooth muscle actin and D2-40. Taking into account morphologic and immunohistochemical features observed in our case, dermatofibroma, fibrous papule/angiofibroma, scar, keloid, dermatofibrosarcoma protuberans, giant cell fibroblastoma, solitary fibrous tumor, hemangiopericytoma, Kaposi’s sar- coma, sclerosing perineurioma, dermal lipoma, end-stage of an inflammatory condition, pleomorphic fibroma and sclerotic fibroma have been considered in the differential diagnosis. Dermatofibroma (DF) may exhibit hyaline and hypocel- lular areas. According to some authors, SF could represent an ancient or degenerated stage of DF [4,5], but lacks other classical architectural signs of it, as preferential limb location, hyperplastic epidermis, infiltrative growth pattern, sometimes Figure 2F. Discrete condensation of the surround collagen and pres- ence of a dilated follicular structure included in the neoplastic pro- liferation, in which vellus hair shafts are seen (Gomori’s trichrome stain x100). [Copyright: ©2015 Miranda et al.] Figure 2G. Spindle and histiocytoid cell proliferation in a sclerotic stroma along with ectatic vessels (H&E x100). [Copyright: ©2015 Miranda et al.] Figure 3. Diffuse CD34 expression by neoplastic cells (immunoper- oxidase x100). [Copyright: ©2015 Miranda et al.] 20 Quiz | Dermatol Pract Concept 2015;5(4):5 trum PF/PSF/SF. The presence of follicle remnants [18] seen in the histopathologic picture (Figures 1B, 2F), a finding in general not referred for SF [6], cannot rule out the role of an eventual previous inflammatory trigger for this case, such as acne or folliculitis. Acknowledgments The authors wish to acknowledge Consultoria em Patologia staff, Botucatu, SP, Brazil, for their excellent technical assis- tance in performing immunohistochemical stains. References 1. Mahmood MN, Salama ME, Chaffins M, et al. Solitary sclerotic fibroma of skin: a possible link with pleomorphic fibroma with immunophenotypic expression for O13 (CD99) and CD34. J Cutan Pathol. 2003;30:631-6. 2. Sánchez MH, Fernández RS, Heredero MC, et al. Sclerotic fibro- ma. Dermatology. 1998;196:429–30. 3. Bhambri S, Bhambri A, Del Rosso JO. Solitary sclerotic fibroma. J Clin Aesth Dermatol. 2009;2:36-8. 4. Cohen PR, Tschen JA, Abaya-Blas R, Cochran RJ. Recurrent sclerotic fibroma of the skin. Am J Dermatopathol. 1999;21:51-4. 5. Sohn IB, Hwang SM, Lee SH, et al. Dermatofibroma with sclerotic areas resembling a sclerotic fibroma of the skin. J Cutan Pathol. 2002;29:44-7. 6. Abbas O, Ghosn S, Rahhady R, et al. Solitary sclerotic fibroma on the scalp of a young girl: reactive sclerosis pattern? (Letter). J Dermatol 2010;37:575–7. 7. High WA, Stewart D, Essary LR, et al. Sclerotic fibroma-like change in various neoplastic and inflammatory skin lesions: is sclerotic fibroma a distinct entity? J Cutan Pathol. 2004;31:373–8. 8. Tardio JC. CD34-reactive tumors of the skin. An updated review of an ever-growing list of lesions. J Cutan Pathol. 2009;36:89– 102. 9. Alawi F, Freedman PD. Sporadic sclerotic fibroma of the oral soft tissues. Am J Dermatopathol. 2004;26:182-7. 10. Chen TM, Purohit SK, Wang AR. Pleomorphic sclerotic fi- broma: a case report and literature review. Am J Dermatopathol. 2002;24:54-8. 11. Val-Bernal JF, González-Vela MC, De Grado M, et al. Sclerotic fi- broma (storiform collagenoma)-like stroma in a fibroadenoma of axillary accessory breast tissue. J Cutan Pathol. 2012;39:798–802. 12. Weyers W, Menzel T, Kasper RC, et al. Fibrous, fibrohistiocytic and histiocytic tumours. In: LeBoit P, Burg G, Weedon D et al. WHO Pathology & Genetics Skin Tumours. Lyon; IARC Press. 2006:254-62. 13. Hansen T, Katenkamp K, Katenkamp D. D2-40 staining in sinonasal-type hemangiopericytoma--further evidence of distinc- tion from conventional hemangiopericytoma and solitary fibrous tumor. Virchows Arch. 2006;448:459-62. 14. Kahn HJ, Bailey D, Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi’s sarcoma and a subset of angiosarcomas. Mod Pathol. 2002;15:434-40. 15. Kaku Y, Fukumoto T, Louise Opada G, et al. A clinicopathological and immunohistochemical study of 7 cases of sclerosing perineu- rioma. Am J Dermatopathol. 2015;37:122-8. nuclei conglomerated toward the center or arranged periph- erally. The stroma may vary from myxoid to collagenous to sclerotic. Angioectoid lymphangioma-like spaces and immu- noreactivity with CD34 are also seen [12]. Solitary fibrous tumor (SFT) of the skin is a very uncom- mon lesion consisting of alternating hypercellular and hypo- cellular areas of bland spindle cells, arranged in a combina- tion of fascicular, storiform and hemangiopericytoma-like vascular patterns in thick hyalinized collagen. Like SF, SFT is diffusely CD34 positive. Subsets of hemangiopericytoma (HP) and SFT are closely related neoplasms (HP/SFT fam- ily). HP may present with either positive or negative D2-40 immunostaining [13]. Areas of diffuse proliferation of spindle cells intermingled with vessels, as observed in the present case (Figure 2G), also recommended the exclusion of Kaposi’s sarcoma (KS), in which a typical morphology and D2-40 positivity would be expected to occur [14]. KS is also often positive to anti-HHV8. Sclerosing perineurioma (SP), like SF, show hypocellular areas, however, usually occurs on hands and feet, and does not react with CD34 [15]. Dermal lipoma with prominent sclerosis may simulate a SF, but mature adipocytes are always demonstrated in the former lesion [16]. Focal changes simu- lating SF may also be seen in inflammatory conditions such as erythema elevatum diutinum and folliculitis [17]. Many histological and immunohistochemical features present in a pleomorphic fibroma (PF), as dermal circum- scription, epidermal atrophy, expansile growth pattern, and prominent clefted “plywood” appearance, were focally seen in one series [1]. The term “pleomorphic SF” (PSF) was fur- ther coined for lesions presenting histological features of PF in the superficial portion of the dermal nodule, SF features in the deeper portion, and positive or negative CD34 immunolabel- ing. Based on these findings, it has been proposed that PF, PSF and SF are components of one spectrum [1,10]. SF—also known as storiform collagenoma, hypocellular fibroma and “plywood” fibroma—is an uncommon benign neoplasm with fibroblastic/dermal dendrocytic differentia- tion first described in association with Cowden’s disease, an autosomal-dominant familial cancer syndrome (multiple hamartoma and neoplasia syndrome) involving the PTEN tumor suppressor gene on chromosome 10q; in such cases, SF often occurs as multiple papules or nodules either on the oral mucosa or the skin [4,10,16,17]. Clinically SF is an asymptomatic, dome-shaped and well-circumscribed lesion of hard consistency [17]. Further SF cases, mostly solitary and on the skin, were observed in patients not affected by Cowden’s disease [9]. In conclusion, we believe our patient has fulfilled chief histopathological criteria, including CD34 reactivity (Figure 3) [1,8], for a diagnosis of SF to be made. We also speculate our case could be inserted into the mid-portion of the spec- Quiz | Dermatol Pract Concept 2015;5(4):5 21 18. Sung-Nam C, Soo II C, Tae Kee M, et al. Sclerotic fibroma of the skin: degenerated sclerotic change of inflammatory conditions especially folliculitis. Am J Dermatopathol. 2000;22:22-5. 16. Calonje E, Lazer A, Brenn T. Storiform collagenoma. In: McKee’s Pathology of the Skin. 4th ed. China; Saunders, 2012:1614-5. 17. Franco GN, Garibay JAR, González MG. Fibroma esclerótico. Comunicación de 16 casos. Estudio clínico-patológico y revisón del tema. Dermatol Ver Mex. 2013;57:104-10.