EXTRAORDINARY CASE REPORT
Follicular Induction Overlying a Dermatofibrosarcoma Protuberans Hai-Jin Park, MD, PhD,* Jennifer V. Nguyen, MD,† Christopher J. Miller, MD,† Walter M. Klein, MD,‡ Adam I. Rubin, MD,† and Rosalie Elenitsas, MD†
Abstract: The term “induction” has been used to describe epidermal changes overlying a dermatofibroma (DF). Follicular induction is most often associated with DF, but can be observed in other lesions, including focal mucinosis, nevus sebaceous, seborrheic keratosis, wart, neurofibroma, and scars. Dermatofibrosarcoma protuberans (DFSP) is a malignant fibrohistiocytic tumor that may be difficult to distinguish from DF. In contrast to DF, the epidermis overlying DFSP is usually attenuated or ulcerated. Here, we report a case of DFSP exhibiting follicular induction of the overlying epidermis. This epidermal change has been rarely reported in DFSP and may present a diagnostic pitfall in superficially sampled lesions. Key Words: dermatofibroma, dermatofibrosarcoma protuberans, follicular induction, giant cell fibroblastoma, hair follicle differentiation (Am J Dermatopathol 2014;36:186–188)
INTRODUCTION
The term “induction” has been used to describe epidermal changes overlying a dermatofibroma (DF).1 These changes include simple acanthosis, seborrheic keratosis-like changes, and basaloid/follicular or sebaceous differentiation.2–5 It is believed that mediators released from fibroblasts interact with and activate keratinocytes resulting in the epidermal changes.6,7 Hair follicle differentiation in the overlying epidermis has been reported in 5%–11% of DF.2,4,8 Dermatofibrosarcoma protuberans (DFSP) is a malignant fibrohistiocytic tumor. Giant cell fibroblastoma is considered a juvenile variant of DFSP occurring almost exclusively in children. In contrast to DF, the epidermis overlying DFSP is usually attenuated, and there may not be a clear (Grenz) zone between the epidermis and the tumor.9 However, when a lesion is superficially sampled, differentiating between DF and DFSP may be challenging.
our institution, she underwent a local excision at another hospital and the histopathology was consistent with DFSP. She subsequently underwent a second and third wide local excision, but the tumor was repeatedly present at the deep surgical margins. She was referred to our institution for Mohs micrographic surgery. Her initial excision biopsy revealed a large spindle cell neoplasm that expanded the full thickness of the reticular dermis and infiltrated the subcutaneous fat (Figs. 1, 2A). Multiple small epithelial islands of basaloid cells were noted arising from the base of the epidermis. The basaloid proliferations showed peripheral palisading and an associated spindle cell stroma, resembling hair bulbs (Figs. 2B, C). The dermal tumor was characterized by areas of densely packed relatively small spindle cells, some of which showed a cartwheel arrangement. Other areas were hypocellular associated with thickened hyalinized collagen bundles. Focally, multinucleated giant cells were noted (Fig. 2D). The spindle cells were CD34 positive and negative for MART-1, CD31, and Factor XIIIa (Fig. 2E). Directly adjacent to the epidermal basaloid proliferations, the spindled stromal cells were focally positive for CD34 (Fig. 2F). Scar tissue was not identified in the vicinity of the follicular induction. Based on these collective findings, a diagnosis of DFSP with features of giant cell fibroblastoma was made. The type 1 collagen and platelet-derived growth factor beta fusion gene was detected via fluorescence in situ hybridization. Clear margins were obtained after 5 stages of Mohs surgery.
DISCUSSION
From the *Department of Dermatology, Ilsan Paik Hospital, Inje University School of Medicine, Goyang, South Korea; †Department of Dermatology, University of Pennsylvania, Philadelphia, PA; and ‡Department of Pathology, Main Line Pathology Associates, Bryn Mawr Hospital, Bryn Mawr, PA. The authors declare no conflicts of interest. Reprints: Hai-Jin Park, MD, PhD, Department of Dermatology, Inje University Ilsan Paik Hospital, 2240 Daehwa-dong, Ilsanseo-gu, Goyang, Kyunggi-do, Republic of Korea (e-mail: [email protected]). © 2014 Lippincott Williams & Wilkins
The common variant of DF is an ill-defined dermal lesion that is largely composed of interlacing fascicles of slender spindled cells. Spindle cells usually extend between collagen bundles with apparent “wrapping” of collagen fibers at the periphery. In addition to the dermal fibrohistiocytic proliferation, epithelial changes are considered an important diagnostic feature in DF. Acanthosis, sometimes with basal layer hyperpigmentation, is present in approximately 70% of lesions.8 Also, there is a spectrum of distinctive epidermal changes ranging from basaloid hyperplasia, often with the formation of rudimentary pilar structures, to basal cell carcinoma.2,4,8 Induction of adnexal differentiation has been reported in 41% of cases,4 and sebaceous differentiation has been observed in 31.6%–33% of cases.2–5,8 DFSP is characterized by uniform spindle cells showing a storiform pattern. DFSP has an infiltrative growth pattern in the dermis and subcutis, classically yielding a honeycomb pattern. Cellular DFs may also extend into subcutis, predominantly along septae, but more typically have a well-demarcated bulging deep margin. In contrast to the characteristic hyperplastic epidermis overlying a DF, the epidermis overlying DFSP is usually attenuated or ulcerated.9 CD34 staining is usually diffusely positive in DFSP and negative in most forms of DF,10–12 whereas factor XIIIa is strongly
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CASE REPORT
A 14-year-old women presented with a firm pink plaque on her posterior neck. The lesion was noted when she was adopted at 1.5 years of age, and had been stable in size. Before presentation at
| www.amjdermatopathology.com
Am J Dermatopathol Volume 36, Number 2, February 2014
FIGURE 1. A large spindle cell neoplasm expands the full thickness of the dermis and infiltrates the subcutis with multiple overlying small epithelial islands of basaloid cells (hematoxylin and eosin; ·20).
expressed in 95% of DF and 15% of DFSP.13 However, these immunohistochemical markers are not specific, as DF can demonstrate variable expression of CD34.14 Indeterminate fibrohistiocytic lesions of the skin have also been described, which show overlap features of DF and DFSP, including epidermal acanthosis, keloidal collagen, densely cellular fascicles with focal storiform areas, and infiltration in the subcutis in a honeycomb pattern. These lesions demonstrate strong labeling of both factor XIIIa and CD34.14 A recent study did not show the presence of the type 1 collagen and platelet-derived growth factor beta chimeric transcript in these indeterminate fibrohistiocytic lesions of the skin, which is characteristic of DFSP.15
Follicular Induction Overlying a DFSP
To obtain additional information regarding the frequency of follicular induction overlying DFSP, we reviewed previous biopsy specimens of DFSP from our institution over the past 8 years. A total of 28 cases were identified, and each was examined by 3 board-certified dermatopathologists (R.E., J.N., A.R.) for the presence of follicular induction. None of the cases demonstrated prominent follicular induction as described in the current case. Two specimens showed very focal findings of a single basaloid epidermal proliferation limited to one rete overlying the tumor, which could reflect early follicular induction. In 1996, Requena et al16 reviewed cutaneous hyperplasia induced by altered stroma. They classified cutaneous hyperplasia into 3 categories as follows: (1) epidermal hyperplasia, (2) pseudocarcinomatous hyperplasia, and (3) adnexal hyperplasia with follicular, sebaceous, or ductal differentiation. They noted that follicular induction could be seen overlying lesions of DF, DFSP, focal mucinosis, nevus sebaceous, seborrheic keratosis, wart, neurofibroma, scar, angioma, anetodermic pilomatricoma, and chronic lymphedema. However, until recently, only 1 case of DFSP with overlying basal cell carcinoma on the left ear was reported.17 The authors suggested that this coexistence of DFSP and basal cell carcinoma was likely incidental, as the latter commonly occurs on sun-exposed skin. Ackerman et al18 reviewed “induction of follicles” and illustrated 1 case of DFSP with follicular induction. They suggested that mesenchymal cells positioned in the upper dermis may behave as embryonic mesenchyme and induce the formation of primitive, partially mature, or fully mature hair follicles and sebaceous glands.
FIGURE 2. A, Densely packed spindle cells are present and diffusely infiltrated into the subcutis yielding a honeycomb pattern (hematoxylin and eosin; ·40). B and C, Multiple small epithelial islands of basaloid cells with palisading and associated spindled cells, resembling hair bulbs (hematoxylin and eosin; ·100 and ·200). D, In a few foci, multinucleated giant cells are observed (hematoxylin and eosin; ·400). E, Spindle cells are CD34 positive (·100). F, Directly adjacent to the epidermal basaloid proliferations, the spindled stromal cells are focally positive for CD34 (·200). 2014 Lippincott Williams & Wilkins
www.amjdermatopathology.com |
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Am J Dermatopathol Volume 36, Number 2, February 2014
Most authors agree that local mediators, including epidermal growth factor released from fibroblasts, stimulate epidermal keratinocytes to induce hair follicle formation and epidermal hyperplasia overlying a DF.6,7,19 Schoenfeld8 first proposed that a “mesenchymal factor” induced such epidermal changes. Requena et al16 suggested that several types of epithelial hyperplasia and neoplasia may be the result of induction of pluripotential germinative cells by stromal stimuli. Variable expression of epidermal growth factor receptor, metallothionein, Ki-67, and keratins 1, 6, and 14 have been shown in fibrohistiocytic processes through the evolution of the dermal lesions, suggesting that these factors may trigger the induction of simple hyperplastic epidermis and mediate deregulated keratinocyte differentiation to basaloid hyperplastic epidermis.6,7 Leong et al20 suggested that basal cell carcinoma–like proliferations seen with DFs may be related to loss of heterozygosity at the Patched locus. In the case of sebaceous differentiation overlying DF, upregulation of the epidermal growth factor–epidermal growth factor receptor and the Hedgehog (HH)-PTCH signaling pathways may be involved.21,22 Ishida et al23 reported a case of follicular induction by metastatic gastric carcinoma and they proposed that molecular factors produced by metastatic gastric carcinoma cells may be able to induce primitive follicular structures. Poblet and Jimenez24 showed that the dermal condensate and the perifollicular spindle-shaped cells in the initial stages of hair formation are CD34 positive. Interestingly, in our case of DFSP, the stromal cells directly surrounding the epidermal basaloid proliferations were positive for CD34, suggesting that the process of follicular induction recapitulates early hair follicle development. However, this finding is not specific and can be observed in both benign and malignant neoplasms that demonstrate follicular induction. In conclusion, follicular inductive changes can be rarely observed overlying DFSP and may be underrecognized, thus representing a diagnostic pitfall in superficially sampled lesions. Dermatopathologists should be aware of this potential histologic feature and consider DFSP if the routine hematoxylin and eosin histopathology is not characteristic for DF. Deeper sampling to include the deep dermis and subcutis may be required if superficial lesions are insufficient for diagnosis.
4. Shuweiter M, Boer A. Spectrum of follicular and sebaceous differentiation induced by dermatofibroma. Am J Dermatopathol. 2009;31:778–785. 5. Requena L, Roo E, Sanchez Yus E. Plate-like sebaceous hyperplasia overlying dermatofibroma. J Cutan Pathol. 1992;19:253–255. 6. Han KH, Huh CH, Cho KH. Proliferation and differentiation of the keratinocytes in hyperplastic epidermis overlying dermatofibroma: immunohistochemical characterization. Am J Dermatopathol. 2001;23: 90–98. 7. Morgan MB, Howard HG, Everett MA. Epithelial induction in dermatofibroma: a role for the epidermal growth factor (EGF) receptor. Am J Dermatopathol. 1997;19:35–40. 8. Schoenfeld RJ. Epidermal proliferations overying histiocytomas. Arch Dermatol. 1964;90:266–270. 9. Beer TW, Lam MH, Heenan PH. Tumors of fibrous tissue involving the skin. In: Elder DE, ed. Lever’s Histopathology of the Skin. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:969–1005. 10. Aiba S, Tabata N, Ishii H, et al. Dermatofibrosarcoma protuberans is a unique fibrohistiocytic tumour expressing CD34. Br J Dermatol. 1992;127:79–84. 11. Altman DA, Nickoloff BJ, Fivenson DP. Differential expression of factor XIIIa and CD34 in cutaneous mesenchymal tumors. J Cutan Pathol. 1993;20:154–158. 12. Weiss SW, Nickoloff BJ. CD-34 is expressed by a distinctive cell population in peripheral nerve, nerve sheath tumors, and related lesions. Am J Surg Pathol. 1993;17:1039–1045. 13. Kahn HJ, Fekete E, From L. Tenascin differentiates dermatofibroma from dermatofibrosarcoma protuberans: comparison with CD34 and factor XIIIa. Hum Pathol. 2001;32:50–56. 14. Horenstein MG, Prieto VG, Nuckols JD, et al. Indeterminate fibrohistiocytic lesions of the skin: is there a spectrum between dermatofibroma and dermatofibrosarcoma protuberans? Am J Surg Pathol. 2000;24:996–1003. 15. Wang WL, Patel KU, Coleman NM, et al. COL1A1:PDGFB chimeric transcripts are not present in indeterminate fibrohistiocytic lesions of the skin. Am J Dermatopathol. 2010;32:149–153. 16. Requena L, Yus ES, Simon P, et al. Induction of cutaneous hyperplasias by altered stroma. Am J Dermatopathol. 1996;18:248–268. 17. Ibrahiem K, Radhi JM. Dermatofibrosarcoma protuberans and basal cell carcinoma. Acta Derm Venereol. 1998;78:233. 18. Ackerman AB, de Viragh PA, Chongchitnant N. Induction of follicle. In: Neoplasm With Follicular Differentiation. Philadelphia, PA: Lea & Febiger; 1993:281–306. 19. Kikuchi A, Sakuraoka K, Shimizu H, et al. Immunohistochemical evaluation of epidermis overlying basal cell carcinomas. Br J Dermatol. 1993;128:644–649. 20. Leong PM, Kauffman CL, Moresi JM, et al. Basal cell carcinoma-like epidermal changes overlying dermatofibromas often reveal loss of heterozygosity in the PTCH gene. J Invest Dermatol. 1999;113:279–280. 21. Yoneda K, Demitsu T, Matsuda Y, et al. Possible molecular pathogenesis for plate-like sebaceous hyperplasia overlying dermatofibroma. Br J Dermatol. 2008;158:840–842. 22. Niemann C, Unden AB, Lyle S, et al. Indian hedgehog and beta-catenin signaling: role in the sebaceous lineage of normal and neoplastic mammalian epidermis. Proc Natl Acad Sci U S A. 2003;100(suppl 1): 11873–11880. 23. Ishida M, Okabe H. Follicular induction by metastatic gastric carcinoma. J Cutan Pathol. 2012;39:660–661. 24. Poblet E, Jimenez F. CD10 and CD34 in fetal and adult human hair follicles: dynamic changes in their immunohistochemical expression during embryogenesis and hair cycling. Br J Dermatol. 2008;159:646–652.
REFERENCES 1. Ackerman AB, Boer A. Histopathological Diagnosis of Adnexal Epithelial Neoplasms. Atlas and Text. New York, NY: Ardor Scribendi Ltd; 2007. 2. Dalziel K, Marks R. Hair follicle-like change over histiocytomas. Am J Dermatopathol. 1986;8:462–466. 3. Davis TT, Calilao G, Fretzin D. Sebaceous hyperplasia overlying a dermatofibroma. Am J Dermatopathol. 2006;28:155–157.
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| www.amjdermatopathology.com
2014 Lippincott Williams & Wilkins
Follicular Induction Overlying a Dermatofibrosarcoma Protuberans Hai-Jin Park, MD, PhD,* Jennifer V. Nguyen, MD,† Christopher J. Miller, MD,† Walter M. Klein, MD,‡ Adam I. Rubin, MD,† and Rosalie Elenitsas, MD†
Abstract: The term “induction” has been used to describe epidermal changes overlying a dermatofibroma (DF). Follicular induction is most often associated with DF, but can be observed in other lesions, including focal mucinosis, nevus sebaceous, seborrheic keratosis, wart, neurofibroma, and scars. Dermatofibrosarcoma protuberans (DFSP) is a malignant fibrohistiocytic tumor that may be difficult to distinguish from DF. In contrast to DF, the epidermis overlying DFSP is usually attenuated or ulcerated. Here, we report a case of DFSP exhibiting follicular induction of the overlying epidermis. This epidermal change has been rarely reported in DFSP and may present a diagnostic pitfall in superficially sampled lesions. Key Words: dermatofibroma, dermatofibrosarcoma protuberans, follicular induction, giant cell fibroblastoma, hair follicle differentiation (Am J Dermatopathol 2014;36:186–188)
INTRODUCTION
The term “induction” has been used to describe epidermal changes overlying a dermatofibroma (DF).1 These changes include simple acanthosis, seborrheic keratosis-like changes, and basaloid/follicular or sebaceous differentiation.2–5 It is believed that mediators released from fibroblasts interact with and activate keratinocytes resulting in the epidermal changes.6,7 Hair follicle differentiation in the overlying epidermis has been reported in 5%–11% of DF.2,4,8 Dermatofibrosarcoma protuberans (DFSP) is a malignant fibrohistiocytic tumor. Giant cell fibroblastoma is considered a juvenile variant of DFSP occurring almost exclusively in children. In contrast to DF, the epidermis overlying DFSP is usually attenuated, and there may not be a clear (Grenz) zone between the epidermis and the tumor.9 However, when a lesion is superficially sampled, differentiating between DF and DFSP may be challenging.
our institution, she underwent a local excision at another hospital and the histopathology was consistent with DFSP. She subsequently underwent a second and third wide local excision, but the tumor was repeatedly present at the deep surgical margins. She was referred to our institution for Mohs micrographic surgery. Her initial excision biopsy revealed a large spindle cell neoplasm that expanded the full thickness of the reticular dermis and infiltrated the subcutaneous fat (Figs. 1, 2A). Multiple small epithelial islands of basaloid cells were noted arising from the base of the epidermis. The basaloid proliferations showed peripheral palisading and an associated spindle cell stroma, resembling hair bulbs (Figs. 2B, C). The dermal tumor was characterized by areas of densely packed relatively small spindle cells, some of which showed a cartwheel arrangement. Other areas were hypocellular associated with thickened hyalinized collagen bundles. Focally, multinucleated giant cells were noted (Fig. 2D). The spindle cells were CD34 positive and negative for MART-1, CD31, and Factor XIIIa (Fig. 2E). Directly adjacent to the epidermal basaloid proliferations, the spindled stromal cells were focally positive for CD34 (Fig. 2F). Scar tissue was not identified in the vicinity of the follicular induction. Based on these collective findings, a diagnosis of DFSP with features of giant cell fibroblastoma was made. The type 1 collagen and platelet-derived growth factor beta fusion gene was detected via fluorescence in situ hybridization. Clear margins were obtained after 5 stages of Mohs surgery.
DISCUSSION
From the *Department of Dermatology, Ilsan Paik Hospital, Inje University School of Medicine, Goyang, South Korea; †Department of Dermatology, University of Pennsylvania, Philadelphia, PA; and ‡Department of Pathology, Main Line Pathology Associates, Bryn Mawr Hospital, Bryn Mawr, PA. The authors declare no conflicts of interest. Reprints: Hai-Jin Park, MD, PhD, Department of Dermatology, Inje University Ilsan Paik Hospital, 2240 Daehwa-dong, Ilsanseo-gu, Goyang, Kyunggi-do, Republic of Korea (e-mail: [email protected]). © 2014 Lippincott Williams & Wilkins
The common variant of DF is an ill-defined dermal lesion that is largely composed of interlacing fascicles of slender spindled cells. Spindle cells usually extend between collagen bundles with apparent “wrapping” of collagen fibers at the periphery. In addition to the dermal fibrohistiocytic proliferation, epithelial changes are considered an important diagnostic feature in DF. Acanthosis, sometimes with basal layer hyperpigmentation, is present in approximately 70% of lesions.8 Also, there is a spectrum of distinctive epidermal changes ranging from basaloid hyperplasia, often with the formation of rudimentary pilar structures, to basal cell carcinoma.2,4,8 Induction of adnexal differentiation has been reported in 41% of cases,4 and sebaceous differentiation has been observed in 31.6%–33% of cases.2–5,8 DFSP is characterized by uniform spindle cells showing a storiform pattern. DFSP has an infiltrative growth pattern in the dermis and subcutis, classically yielding a honeycomb pattern. Cellular DFs may also extend into subcutis, predominantly along septae, but more typically have a well-demarcated bulging deep margin. In contrast to the characteristic hyperplastic epidermis overlying a DF, the epidermis overlying DFSP is usually attenuated or ulcerated.9 CD34 staining is usually diffusely positive in DFSP and negative in most forms of DF,10–12 whereas factor XIIIa is strongly
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Am J Dermatopathol Volume 36, Number 2, February 2014
CASE REPORT
A 14-year-old women presented with a firm pink plaque on her posterior neck. The lesion was noted when she was adopted at 1.5 years of age, and had been stable in size. Before presentation at
| www.amjdermatopathology.com
Am J Dermatopathol Volume 36, Number 2, February 2014
FIGURE 1. A large spindle cell neoplasm expands the full thickness of the dermis and infiltrates the subcutis with multiple overlying small epithelial islands of basaloid cells (hematoxylin and eosin; ·20).
expressed in 95% of DF and 15% of DFSP.13 However, these immunohistochemical markers are not specific, as DF can demonstrate variable expression of CD34.14 Indeterminate fibrohistiocytic lesions of the skin have also been described, which show overlap features of DF and DFSP, including epidermal acanthosis, keloidal collagen, densely cellular fascicles with focal storiform areas, and infiltration in the subcutis in a honeycomb pattern. These lesions demonstrate strong labeling of both factor XIIIa and CD34.14 A recent study did not show the presence of the type 1 collagen and platelet-derived growth factor beta chimeric transcript in these indeterminate fibrohistiocytic lesions of the skin, which is characteristic of DFSP.15
Follicular Induction Overlying a DFSP
To obtain additional information regarding the frequency of follicular induction overlying DFSP, we reviewed previous biopsy specimens of DFSP from our institution over the past 8 years. A total of 28 cases were identified, and each was examined by 3 board-certified dermatopathologists (R.E., J.N., A.R.) for the presence of follicular induction. None of the cases demonstrated prominent follicular induction as described in the current case. Two specimens showed very focal findings of a single basaloid epidermal proliferation limited to one rete overlying the tumor, which could reflect early follicular induction. In 1996, Requena et al16 reviewed cutaneous hyperplasia induced by altered stroma. They classified cutaneous hyperplasia into 3 categories as follows: (1) epidermal hyperplasia, (2) pseudocarcinomatous hyperplasia, and (3) adnexal hyperplasia with follicular, sebaceous, or ductal differentiation. They noted that follicular induction could be seen overlying lesions of DF, DFSP, focal mucinosis, nevus sebaceous, seborrheic keratosis, wart, neurofibroma, scar, angioma, anetodermic pilomatricoma, and chronic lymphedema. However, until recently, only 1 case of DFSP with overlying basal cell carcinoma on the left ear was reported.17 The authors suggested that this coexistence of DFSP and basal cell carcinoma was likely incidental, as the latter commonly occurs on sun-exposed skin. Ackerman et al18 reviewed “induction of follicles” and illustrated 1 case of DFSP with follicular induction. They suggested that mesenchymal cells positioned in the upper dermis may behave as embryonic mesenchyme and induce the formation of primitive, partially mature, or fully mature hair follicles and sebaceous glands.
FIGURE 2. A, Densely packed spindle cells are present and diffusely infiltrated into the subcutis yielding a honeycomb pattern (hematoxylin and eosin; ·40). B and C, Multiple small epithelial islands of basaloid cells with palisading and associated spindled cells, resembling hair bulbs (hematoxylin and eosin; ·100 and ·200). D, In a few foci, multinucleated giant cells are observed (hematoxylin and eosin; ·400). E, Spindle cells are CD34 positive (·100). F, Directly adjacent to the epidermal basaloid proliferations, the spindled stromal cells are focally positive for CD34 (·200). 2014 Lippincott Williams & Wilkins
www.amjdermatopathology.com |
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Park et al
Am J Dermatopathol Volume 36, Number 2, February 2014
Most authors agree that local mediators, including epidermal growth factor released from fibroblasts, stimulate epidermal keratinocytes to induce hair follicle formation and epidermal hyperplasia overlying a DF.6,7,19 Schoenfeld8 first proposed that a “mesenchymal factor” induced such epidermal changes. Requena et al16 suggested that several types of epithelial hyperplasia and neoplasia may be the result of induction of pluripotential germinative cells by stromal stimuli. Variable expression of epidermal growth factor receptor, metallothionein, Ki-67, and keratins 1, 6, and 14 have been shown in fibrohistiocytic processes through the evolution of the dermal lesions, suggesting that these factors may trigger the induction of simple hyperplastic epidermis and mediate deregulated keratinocyte differentiation to basaloid hyperplastic epidermis.6,7 Leong et al20 suggested that basal cell carcinoma–like proliferations seen with DFs may be related to loss of heterozygosity at the Patched locus. In the case of sebaceous differentiation overlying DF, upregulation of the epidermal growth factor–epidermal growth factor receptor and the Hedgehog (HH)-PTCH signaling pathways may be involved.21,22 Ishida et al23 reported a case of follicular induction by metastatic gastric carcinoma and they proposed that molecular factors produced by metastatic gastric carcinoma cells may be able to induce primitive follicular structures. Poblet and Jimenez24 showed that the dermal condensate and the perifollicular spindle-shaped cells in the initial stages of hair formation are CD34 positive. Interestingly, in our case of DFSP, the stromal cells directly surrounding the epidermal basaloid proliferations were positive for CD34, suggesting that the process of follicular induction recapitulates early hair follicle development. However, this finding is not specific and can be observed in both benign and malignant neoplasms that demonstrate follicular induction. In conclusion, follicular inductive changes can be rarely observed overlying DFSP and may be underrecognized, thus representing a diagnostic pitfall in superficially sampled lesions. Dermatopathologists should be aware of this potential histologic feature and consider DFSP if the routine hematoxylin and eosin histopathology is not characteristic for DF. Deeper sampling to include the deep dermis and subcutis may be required if superficial lesions are insufficient for diagnosis.
4. Shuweiter M, Boer A. Spectrum of follicular and sebaceous differentiation induced by dermatofibroma. Am J Dermatopathol. 2009;31:778–785. 5. Requena L, Roo E, Sanchez Yus E. Plate-like sebaceous hyperplasia overlying dermatofibroma. J Cutan Pathol. 1992;19:253–255. 6. Han KH, Huh CH, Cho KH. Proliferation and differentiation of the keratinocytes in hyperplastic epidermis overlying dermatofibroma: immunohistochemical characterization. Am J Dermatopathol. 2001;23: 90–98. 7. Morgan MB, Howard HG, Everett MA. Epithelial induction in dermatofibroma: a role for the epidermal growth factor (EGF) receptor. Am J Dermatopathol. 1997;19:35–40. 8. Schoenfeld RJ. Epidermal proliferations overying histiocytomas. Arch Dermatol. 1964;90:266–270. 9. Beer TW, Lam MH, Heenan PH. Tumors of fibrous tissue involving the skin. In: Elder DE, ed. Lever’s Histopathology of the Skin. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:969–1005. 10. Aiba S, Tabata N, Ishii H, et al. Dermatofibrosarcoma protuberans is a unique fibrohistiocytic tumour expressing CD34. Br J Dermatol. 1992;127:79–84. 11. Altman DA, Nickoloff BJ, Fivenson DP. Differential expression of factor XIIIa and CD34 in cutaneous mesenchymal tumors. J Cutan Pathol. 1993;20:154–158. 12. Weiss SW, Nickoloff BJ. CD-34 is expressed by a distinctive cell population in peripheral nerve, nerve sheath tumors, and related lesions. Am J Surg Pathol. 1993;17:1039–1045. 13. Kahn HJ, Fekete E, From L. Tenascin differentiates dermatofibroma from dermatofibrosarcoma protuberans: comparison with CD34 and factor XIIIa. Hum Pathol. 2001;32:50–56. 14. Horenstein MG, Prieto VG, Nuckols JD, et al. Indeterminate fibrohistiocytic lesions of the skin: is there a spectrum between dermatofibroma and dermatofibrosarcoma protuberans? Am J Surg Pathol. 2000;24:996–1003. 15. Wang WL, Patel KU, Coleman NM, et al. COL1A1:PDGFB chimeric transcripts are not present in indeterminate fibrohistiocytic lesions of the skin. Am J Dermatopathol. 2010;32:149–153. 16. Requena L, Yus ES, Simon P, et al. Induction of cutaneous hyperplasias by altered stroma. Am J Dermatopathol. 1996;18:248–268. 17. Ibrahiem K, Radhi JM. Dermatofibrosarcoma protuberans and basal cell carcinoma. Acta Derm Venereol. 1998;78:233. 18. Ackerman AB, de Viragh PA, Chongchitnant N. Induction of follicle. In: Neoplasm With Follicular Differentiation. Philadelphia, PA: Lea & Febiger; 1993:281–306. 19. Kikuchi A, Sakuraoka K, Shimizu H, et al. Immunohistochemical evaluation of epidermis overlying basal cell carcinomas. Br J Dermatol. 1993;128:644–649. 20. Leong PM, Kauffman CL, Moresi JM, et al. Basal cell carcinoma-like epidermal changes overlying dermatofibromas often reveal loss of heterozygosity in the PTCH gene. J Invest Dermatol. 1999;113:279–280. 21. Yoneda K, Demitsu T, Matsuda Y, et al. Possible molecular pathogenesis for plate-like sebaceous hyperplasia overlying dermatofibroma. Br J Dermatol. 2008;158:840–842. 22. Niemann C, Unden AB, Lyle S, et al. Indian hedgehog and beta-catenin signaling: role in the sebaceous lineage of normal and neoplastic mammalian epidermis. Proc Natl Acad Sci U S A. 2003;100(suppl 1): 11873–11880. 23. Ishida M, Okabe H. Follicular induction by metastatic gastric carcinoma. J Cutan Pathol. 2012;39:660–661. 24. Poblet E, Jimenez F. CD10 and CD34 in fetal and adult human hair follicles: dynamic changes in their immunohistochemical expression during embryogenesis and hair cycling. Br J Dermatol. 2008;159:646–652.
REFERENCES 1. Ackerman AB, Boer A. Histopathological Diagnosis of Adnexal Epithelial Neoplasms. Atlas and Text. New York, NY: Ardor Scribendi Ltd; 2007. 2. Dalziel K, Marks R. Hair follicle-like change over histiocytomas. Am J Dermatopathol. 1986;8:462–466. 3. Davis TT, Calilao G, Fretzin D. Sebaceous hyperplasia overlying a dermatofibroma. Am J Dermatopathol. 2006;28:155–157.
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2014 Lippincott Williams & Wilkins
