J Cutan Pathol 2015: 42: 652–656 doi: 10.1111/cup.12497 John Wiley & Sons. Printed in Singapore
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Journal of Cutaneous Pathology
Multibranched acquired periungual fibrokeratomas with confounding histopathologic findings resembling papillomavirus infection: a report of two cases Acquired periungual fibrokeratomas are benign fibrous tissue tumors and are considered as the topographical variant of acquired digital fibrokeratoma. They usually present as solitary tumors. In some instance, the entity may appear in multibranched fashion. The main histopathologic features consist of acanthosis, thick collagen bundles mainly oriented in a vertical axis forming a central core, and numerous proliferating fibroblasts. In this article, we present two cases of acquired multibranched periungual fibrokeratoma and depict their varying clinical features over time. Binucleation and perinuclear halos of keratinocytes mimicking human papillomavirus (HPV) infection were detected microscopically, but there was no reactivity with HPV immunostaining. In context, anti-HPV immunostaining may be helpful in the differentiation of fibrokeratomas from HPV infection. On the other hand, it should be kept in mind that these histopathologic findings may be found in acral biopsies independent of viral effects. Keywords: fibrous tissue neoplasm, HPV, immunohistochemistry, nail disease Göktay F, Altan ZM, Haras ZB, Güne¸s P, Ya¸sar S, ¸ Aytekin S, Haneke E. Multibranched acquired periungual fibrokeratomas with confounding histopathologic findings resembling papillomavirus infection: a report of two cases. J Cutan Pathol 2015; 42: 652–656. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Fibrokeratomas are benign tumors of the fibrous tissue.1 In the ungual region, they may originate from periungual skin, under the proximal nail fold and in the matrix or nail bed. Usually, the lesions are solitary but may be multiple in patients with tuberous sclerosis.2 Acquired periungual fibrokeratomas are considered as
652
Fatih Göktay1 , Zeynep Müeyyen Altan1 , Zeynep Bü¸sra Haras1 , Pembegül Güne¸s2 , S¸ irin Ya¸sar1 , Sema Aytekin1 and Eckart Haneke3 1
Department of Dermatology, Haydarpa¸sa Numune Training and Research Hospital, Istanbul, Turkey, 2 Department of Pathology, Haydarpa¸sa Numune Training and Research Hospital, Istanbul, Turkey, and 3 Department of Dermatology, Inselspital Bern University Hospital, Bern, Switzerland
Dr. Fatih Göktay Haydarpa¸sa Numune E˘gitim ve Ara¸stırma Hastanesi, Deri ve Zührevi Hastalıklar Klini˘gi 34668, Üsküdar, Istanbul, Turkey Tel: +90 505 2671399 Fax: +90 216 3360565 e-mail: [email protected] Accepted for publication April 18, 2015
a topographical variant of acquired digital fibrokeratoma.3,4 Clinically acquired periungual fibrokeratoma presents as a firm, pinkish, hyperkeratotic papule protruding under the proximal nail fold. Sometimes, they appear multibranched in this anatomic location.5 A longitudinal groove on the nail plate may
Periungual fibrokeratoma resembling HPV
Fig. 1. A) The clinical appearance at the first admission mimicked pyogenic granuloma; B) clinical and (C) dermoscopic pictures just before the surgical excision showed a multibranched, maggot-like fibrokeratoma; D and E) surgical excision; F) clinical appearance at the end of the 7 months follow-up.
occur because the lesion compresses the nail matrix.6 Viral wart, rudimentary supernumerary digit, onychomatricoma, dermatofibroma, enchondroma, neurofibroma and foreign body granuloma are all considered in the differential diagnosis of acquired digital fibrokeratoma. 7,8 The main histopathologic features of acquired digital fibrokeratoma are acanthosis, thick collagen bundles mainly oriented in the vertical axis of the lesion forming a central core and numerous proliferating fibroblasts locating between these collagen bundles.9 Herein, we present two cases of multibranched acquired periungual fibrokeratoma with histopathologic findings resembling a human papillomavirus (HPV) infection. Patient 1 A 42-year-old female cook presented with a complaint of nail deformation, bleeding and crusts on the proximal end of the left fifth fingernail. The lesion had started as a nail disfigurement and scaling on the proximal nail fold 13 years ago. She did not receive any treatment. Physical examination was within normal limits. At the time of her first consultation, an erythematous papule mimicking pyogenic granuloma or digital myxoid cyst was detected upon clinical evaluation. It was associated with a longitudinal groove in the nail plate (Fig. 1A). About 20 days later, when the patient was admitted for an excisional biopsy, filiform structures were detected instead of an erythematous papule (Fig. 1B). Dermoscopy performed just before excisional biopsy, detected two 2–3 mm thick, skin-colored filiform maggot-like structures with fine hemorrhagic crusts at their tips located between the cuticle and the nail plate (Fig. 1C). Her past medical history was unremarkable. After distal digital wing anesthesia, a lateral incision was made at 45∘ on the proximal nail fold to permit its retraction with the aid of a hook; the lesions
were then dissected and excised with fine iris scissors (Fig. 1D,E). Histopathologic examination of the lesion revealed compact hyperkeratosis, parakeratosis, hypergranulosis, papillomatosis, irregular acanthosis, dermal edema, some perinuclear halo and binucleations of keratinocytes and a dermal core consisting of dense collagen bundles (Fig. 2A,B). Fibrokeratoma and HPV infection were considered in the differential diagnosis of the lesion. HPV expression was not detected with immunohistochemical anti-HPV antibody staining (HPV Cocktail Broad Spectrum, Biocare Medical, CA, USA) (Fig. 2C). A tissue specimen of HPV-induced cervical dysplasia was used as a positive control for immunostaining. The groove on the nail plate improved and there was no recurrence at the end of the seventh month of follow-up (Fig. 1F). Patient 2 A 55-year-old housewife was referred to our outpatient clinic because of painful fleshy tissue protruding from the bottom of her left toenail. This was first seen approximately 2 years prior. In the past, it partially improved after a cure of oral antibiotic therapy. Her past medical history was remarkable for renal cysts, cristalluria, benign hepatic and pulmonary masses, which have been followed up for 10 years, and gastric reflux. On abdominal ultrasonography, three thin-walled anechoic bilateral simple renal cortical cysts with diameters ranging from 12 to 22 mm were detected. Scintigraphy with 20 mCi Tc-99 m PYP-labeled erythrocytes found a hepatic mass consistent with hemangioma. Two ovoidal, low density pulmonary nodules, approximately 4 mm in diameter were detected on the computerized thorax tomography. One of them was localized in the right lung, middle lobe, medial segment, anterolateral peripheral parenchyma, and the other was in
653
Göktay et al.
Fig. 2. A) Scanning magnification of a typical lesion shows hyperkeratosis, parakeratosis, acanthosis and a dermal core consisting of dense collagen bundles (hematoxylin/eosin). B) There was prominent binucleation (arrow head) and a perinuclear halo of keratinocytes with a pseudokoilocytic appearance (arrows) (hematoxylin/eosin). C) There was negative staining for human papillomavirus (HPV).
Fig. 3. A) The clinical and (B) dermoscopic appearance at the patients’ first admission showed two purplish filiform papules; C) clinical and (D) dermoscopic pictures taken just before the surgical excision show multiple branching papules; E) an excisional biopsy; F) there was a return to an almost totally normal clinical appearance with 8 months follow-up.
the left lung inferior posterolateal subpleural localization. Dermatological examination was unremarkable except for two painful, purplish, erythematous, filiform structures located on the proximal end of the left toenail and a longitudinal groove on the nail plate (Fig. 3A,B). Two months later, just before the surgical excision, four skin-colored filiform structures were observed (Fig. 3C). Dermoscopy showed four multibranched, 2–5 mm thick, skin-colored, finger-like structures between the cuticle and the nail plate. The lesion was excised in the same way of the first case (Fig. 3E). Histopathologic examination revealed hyperkeratosis, parakeratosis, irregular acanthosis, papillomatosis, epithelial proliferation and a core of vertically oriented thick collagen bundles in the dermis (Fig. 4A,B). There was no reactivity with the anti-HPV antibody immunostaining (HPV Cocktail Broad Spectrum, Biocare Medical) (Fig. 4D). As a positive control, a biopsy specimen of HPV-induced cervical dysplasia was used for immunostaining. The nail plate was almost completely normal and there was no recurrence at the end of the eighth month of patient follow-up (Fig. 3F).
654
Discussion The term multibranched acquired periungual fibrokeratoma was first used in a case report by Moriue et al.5 Dermatologic examination of this case revealed two branching asymptomatic, firm skin-colored small rod-like nodules with two branches arising beneath the proximal nail fold. During the excision, the authors noticed a third 2 mm small nodule. Both nodules branched from each other at the bottom of the lesion. The lesion reported by Moriue et al.5 was clinically similar to ours, especially the second of our cases. Some more acquired periungual fibrokeratoma cases showing similar multibranched lesions could be found in the English literature.6,10 It would be more appropriate to consider that the multibranched lesion reported by Moriue’s is a much bigger one than our cases and also the ones reported before6,10 rather than a new clinical entity. Kint et al.11 described the following three variants of acquired digital fibrokeratoma: (i) those with thick, dense, closely packed collagen bundles arranged mostly irregularly or sometimes along with the vertical axis of the lesion containing fibroblasts, numerous capillaries and thin elastic fibers seen usually in the dome-shaped
Periungual fibrokeratoma resembling HPV
Fig. 4. A) Scanning magnification shows hyperkeratosis, acanthosis and papillomatosis (hematoxylin/eosin); B) there is a prominent papillary appearance with hypergranulosis (hematoxylin/eosin); C) there is also hypergranulosis and perinuclear haloes (hematoxylin/eosin); D) negative staining for human papillomavirus (HPV) is illustrated.
tumors. The structure is similar to that of normal connective tissue; (ii) those with thick, closely packed collagen bundles oriented along the vertical axis of the lesion with decreased number of elastic fibers and increased number of fibroblasts. The structure is different from that of normal connective tissue and clinically seen as tall and hyperkeratotic lesions; and (iii) those presenting as flat to dome-shaped lesions that show very thin, few, irregularly arranged collagen bundles containing a few fibroblasts and lacking elastic fibers in an edematous structure with surrounding dermal edema. A hyperkeratotic stratum corneum is seen in all these three variants. In both of our cases, histopathology showed closely packed collagen bundles extending perpendicularly to the surface of the epidermis. In the stroma, the appearance of vessels, fibroblasts and thin elastic fibers was similar to those in the normal dermis. According to these findings, the histopathologic characteristics of our cases correspond to the between histopathologic type described by Kint et al. 11 In another study, Kint et al.12 investigated the histopathologic features of Koenen tumors. In this study, they also discussed whether these lesions are different from acquired digital fibrokeratoma or not. Histopathologic examination revealed capillaries surrounded by thin collagen
fibers in the distal part of the lesions and fibroblasts with fusiform nuclei among the dense, closely packed collagen fibers in the core of the lesions. There were no neural cells. The authors suggested that the histopathologic findings of these tumors resemble those of acquired digital fibrokeratoma, and they considered Koenen tumors as a particular type of fibrokeratoma. In this context, according to clinical appearance, localization and origin, the lesions can be subclassified into the following two groups: (i) acquired digital fibrokeratoma on the digits originating from the dermal connective tissue and (ii) congenital (tuberous sclerosis) or acquired fibrokeratomas originating from the proximal nail fold or the surrounding connective tissue. According to the recommendations of the International Tuberous Sclerosis Complex Consensus Conference, the presence of two or more ungual fibromas, of two or more angiomyolipomas and of lymphangioleiomyomatosis of the lung are major diagnostic criteria of tuberous sclerosis. Multiple simple renal cysts belong to the minor criteria.13 In the medical history, physical and dermatological examination of our first case showed no remarkable finding associated with tuberous sclerosis. The medical history of our second case revealed benign hepatic and pulmonary masses and renal cysts, which may
655
Göktay et al. possibly be related to tuberous sclerosis. The hepatic mass was found to be a hemangioma, and millimetric nodules in the lung were not an expected finding for tuberous sclerosis. Therefore, in our second case who has only one periungual fibrokeratoma and simple renal cysts, we think that these associations of internal findings and acquired periungual fibrokeratoma may be coincidental. Characteristic histopathologic features of HPV infection consist of hyperkeratosis, hypergranulosis, prominent keratohyaline granules, papillomatosis, acanthosis and ‘parakeratotic columns’ located on the tips of the papillomatous projections. One of the most characteristic histopathologic features of warts is koilocytes. These cells are large vacuolar keratinocytes located in the granular and malpighian layers with clear cytoplasm and small pycnotic nuclei. Eosinophilic viral inclusion bodies may be seen in the cytoplasm of these cells.14 In addition to the type 1 histopathologic findings of fibrokeratoma, we
noticed keratinocytes with binucleation and perinuclear halos considering the diagnosis of HPV infection in our cases. These findings might be associated with a primary HPV infection or secondarily infected fibrokeratomas by HPV, but HPV could not be detected by immunohistochemical analysis. In conclusion, as seen in our cases, acquired periungual fibrokeratomas arising under the proximal nail fold may show varying clinical features over time. Additionally, the multibranched clinical appearance of acquired periungual fibrokeratomas could be a more frequent finding seen in the clinical practice than reported in the literature. Finally, in the presence of histopathologic findings suggesting HPV infection such as papillomatosis, parakeratotic columns located on the top of the papillary structures, binucleation and perinuclear halos of keratinocytes, the histopathologic diagnosis of acquired periungual fibrokeratoma may be confirmed by the absence of HPV staining by immunohistochemical analysis.
References 1. Baykal C, Buyukbabani N, Yazganoglu KD, Saglik E. Acquired digital fibrokeratoma. Cutis 2007; 79: 129. 2. Haneke E. Nail surgery. Clin Dermatol 2013; 31: 516. 3. Kikuchi I, Ishii Y, Inoue S. Acquired periungual fibroma. J Dermatol 1978; 5: 235. 4. Yasuki Y. Acquired periungual fibrokeratoma – a proposal for classification of periungual fibrous lesions. J Dermatol 1985; 12: 349. 5. Moriue T, Yoneda K, Moriue J, Nakai K, Kubota Y. Multibranched acquired periungual fibrokeratoma. JAMA Dermatol 2014; 150: 456.
656
6. Saito S, Ishikawa K. Acquired periungual fibrokeratoma with accessory germinal matrix. J Hand Surg (Br) 2002; 27: 549. 7. Kumari R, Thappa DM, Devi A. Periungual acquired digital fibrokeratoma. Indian J Dermatol Venereol Leprol 2009; 75: 72. 8. Lee CY, Lee KY, Kim KH, Kim YH. Total excision of acquired periungual fibrokeratoma using bilateral proximal nail fold oblique incision for preserving nail matrix. Dermatol Surg 2010; 36: 139. 9. Mahajan D, Billings SD, Goldblum JR. Acral soft tissue tumors: a review. Adv Anat Pathol 2011; 18: 103. 10. Carlson RM, Lloyd KM, Campbell TE. Acquired periungual fibrokeratoma: a case report. Cutis 2007; 80: 137.
11. Kint A, Baran R, De Keyser H. Acquired (digital) fibrokeratoma. J Am Acad Dermatol 1985; 12: 816. 12. Kint A, Baran R. Histopathologic study of Koenen tumors. Are they different from acquired digital fibrokeratoma? J Am Acad Dermatol 1988; 18: 369. 13. Northrup H, Krueger DA, International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 2013; 49: 243. 14. Weedon D. Weedon’s skin pathology, 3rd ed. Melbourne; Elsevier, 2010pp. 608.
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Journal of Cutaneous Pathology
Multibranched acquired periungual fibrokeratomas with confounding histopathologic findings resembling papillomavirus infection: a report of two cases Acquired periungual fibrokeratomas are benign fibrous tissue tumors and are considered as the topographical variant of acquired digital fibrokeratoma. They usually present as solitary tumors. In some instance, the entity may appear in multibranched fashion. The main histopathologic features consist of acanthosis, thick collagen bundles mainly oriented in a vertical axis forming a central core, and numerous proliferating fibroblasts. In this article, we present two cases of acquired multibranched periungual fibrokeratoma and depict their varying clinical features over time. Binucleation and perinuclear halos of keratinocytes mimicking human papillomavirus (HPV) infection were detected microscopically, but there was no reactivity with HPV immunostaining. In context, anti-HPV immunostaining may be helpful in the differentiation of fibrokeratomas from HPV infection. On the other hand, it should be kept in mind that these histopathologic findings may be found in acral biopsies independent of viral effects. Keywords: fibrous tissue neoplasm, HPV, immunohistochemistry, nail disease Göktay F, Altan ZM, Haras ZB, Güne¸s P, Ya¸sar S, ¸ Aytekin S, Haneke E. Multibranched acquired periungual fibrokeratomas with confounding histopathologic findings resembling papillomavirus infection: a report of two cases. J Cutan Pathol 2015; 42: 652–656. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Fibrokeratomas are benign tumors of the fibrous tissue.1 In the ungual region, they may originate from periungual skin, under the proximal nail fold and in the matrix or nail bed. Usually, the lesions are solitary but may be multiple in patients with tuberous sclerosis.2 Acquired periungual fibrokeratomas are considered as
652
Fatih Göktay1 , Zeynep Müeyyen Altan1 , Zeynep Bü¸sra Haras1 , Pembegül Güne¸s2 , S¸ irin Ya¸sar1 , Sema Aytekin1 and Eckart Haneke3 1
Department of Dermatology, Haydarpa¸sa Numune Training and Research Hospital, Istanbul, Turkey, 2 Department of Pathology, Haydarpa¸sa Numune Training and Research Hospital, Istanbul, Turkey, and 3 Department of Dermatology, Inselspital Bern University Hospital, Bern, Switzerland
Dr. Fatih Göktay Haydarpa¸sa Numune E˘gitim ve Ara¸stırma Hastanesi, Deri ve Zührevi Hastalıklar Klini˘gi 34668, Üsküdar, Istanbul, Turkey Tel: +90 505 2671399 Fax: +90 216 3360565 e-mail: [email protected] Accepted for publication April 18, 2015
a topographical variant of acquired digital fibrokeratoma.3,4 Clinically acquired periungual fibrokeratoma presents as a firm, pinkish, hyperkeratotic papule protruding under the proximal nail fold. Sometimes, they appear multibranched in this anatomic location.5 A longitudinal groove on the nail plate may
Periungual fibrokeratoma resembling HPV
Fig. 1. A) The clinical appearance at the first admission mimicked pyogenic granuloma; B) clinical and (C) dermoscopic pictures just before the surgical excision showed a multibranched, maggot-like fibrokeratoma; D and E) surgical excision; F) clinical appearance at the end of the 7 months follow-up.
occur because the lesion compresses the nail matrix.6 Viral wart, rudimentary supernumerary digit, onychomatricoma, dermatofibroma, enchondroma, neurofibroma and foreign body granuloma are all considered in the differential diagnosis of acquired digital fibrokeratoma. 7,8 The main histopathologic features of acquired digital fibrokeratoma are acanthosis, thick collagen bundles mainly oriented in the vertical axis of the lesion forming a central core and numerous proliferating fibroblasts locating between these collagen bundles.9 Herein, we present two cases of multibranched acquired periungual fibrokeratoma with histopathologic findings resembling a human papillomavirus (HPV) infection. Patient 1 A 42-year-old female cook presented with a complaint of nail deformation, bleeding and crusts on the proximal end of the left fifth fingernail. The lesion had started as a nail disfigurement and scaling on the proximal nail fold 13 years ago. She did not receive any treatment. Physical examination was within normal limits. At the time of her first consultation, an erythematous papule mimicking pyogenic granuloma or digital myxoid cyst was detected upon clinical evaluation. It was associated with a longitudinal groove in the nail plate (Fig. 1A). About 20 days later, when the patient was admitted for an excisional biopsy, filiform structures were detected instead of an erythematous papule (Fig. 1B). Dermoscopy performed just before excisional biopsy, detected two 2–3 mm thick, skin-colored filiform maggot-like structures with fine hemorrhagic crusts at their tips located between the cuticle and the nail plate (Fig. 1C). Her past medical history was unremarkable. After distal digital wing anesthesia, a lateral incision was made at 45∘ on the proximal nail fold to permit its retraction with the aid of a hook; the lesions
were then dissected and excised with fine iris scissors (Fig. 1D,E). Histopathologic examination of the lesion revealed compact hyperkeratosis, parakeratosis, hypergranulosis, papillomatosis, irregular acanthosis, dermal edema, some perinuclear halo and binucleations of keratinocytes and a dermal core consisting of dense collagen bundles (Fig. 2A,B). Fibrokeratoma and HPV infection were considered in the differential diagnosis of the lesion. HPV expression was not detected with immunohistochemical anti-HPV antibody staining (HPV Cocktail Broad Spectrum, Biocare Medical, CA, USA) (Fig. 2C). A tissue specimen of HPV-induced cervical dysplasia was used as a positive control for immunostaining. The groove on the nail plate improved and there was no recurrence at the end of the seventh month of follow-up (Fig. 1F). Patient 2 A 55-year-old housewife was referred to our outpatient clinic because of painful fleshy tissue protruding from the bottom of her left toenail. This was first seen approximately 2 years prior. In the past, it partially improved after a cure of oral antibiotic therapy. Her past medical history was remarkable for renal cysts, cristalluria, benign hepatic and pulmonary masses, which have been followed up for 10 years, and gastric reflux. On abdominal ultrasonography, three thin-walled anechoic bilateral simple renal cortical cysts with diameters ranging from 12 to 22 mm were detected. Scintigraphy with 20 mCi Tc-99 m PYP-labeled erythrocytes found a hepatic mass consistent with hemangioma. Two ovoidal, low density pulmonary nodules, approximately 4 mm in diameter were detected on the computerized thorax tomography. One of them was localized in the right lung, middle lobe, medial segment, anterolateral peripheral parenchyma, and the other was in
653
Göktay et al.
Fig. 2. A) Scanning magnification of a typical lesion shows hyperkeratosis, parakeratosis, acanthosis and a dermal core consisting of dense collagen bundles (hematoxylin/eosin). B) There was prominent binucleation (arrow head) and a perinuclear halo of keratinocytes with a pseudokoilocytic appearance (arrows) (hematoxylin/eosin). C) There was negative staining for human papillomavirus (HPV).
Fig. 3. A) The clinical and (B) dermoscopic appearance at the patients’ first admission showed two purplish filiform papules; C) clinical and (D) dermoscopic pictures taken just before the surgical excision show multiple branching papules; E) an excisional biopsy; F) there was a return to an almost totally normal clinical appearance with 8 months follow-up.
the left lung inferior posterolateal subpleural localization. Dermatological examination was unremarkable except for two painful, purplish, erythematous, filiform structures located on the proximal end of the left toenail and a longitudinal groove on the nail plate (Fig. 3A,B). Two months later, just before the surgical excision, four skin-colored filiform structures were observed (Fig. 3C). Dermoscopy showed four multibranched, 2–5 mm thick, skin-colored, finger-like structures between the cuticle and the nail plate. The lesion was excised in the same way of the first case (Fig. 3E). Histopathologic examination revealed hyperkeratosis, parakeratosis, irregular acanthosis, papillomatosis, epithelial proliferation and a core of vertically oriented thick collagen bundles in the dermis (Fig. 4A,B). There was no reactivity with the anti-HPV antibody immunostaining (HPV Cocktail Broad Spectrum, Biocare Medical) (Fig. 4D). As a positive control, a biopsy specimen of HPV-induced cervical dysplasia was used for immunostaining. The nail plate was almost completely normal and there was no recurrence at the end of the eighth month of patient follow-up (Fig. 3F).
654
Discussion The term multibranched acquired periungual fibrokeratoma was first used in a case report by Moriue et al.5 Dermatologic examination of this case revealed two branching asymptomatic, firm skin-colored small rod-like nodules with two branches arising beneath the proximal nail fold. During the excision, the authors noticed a third 2 mm small nodule. Both nodules branched from each other at the bottom of the lesion. The lesion reported by Moriue et al.5 was clinically similar to ours, especially the second of our cases. Some more acquired periungual fibrokeratoma cases showing similar multibranched lesions could be found in the English literature.6,10 It would be more appropriate to consider that the multibranched lesion reported by Moriue’s is a much bigger one than our cases and also the ones reported before6,10 rather than a new clinical entity. Kint et al.11 described the following three variants of acquired digital fibrokeratoma: (i) those with thick, dense, closely packed collagen bundles arranged mostly irregularly or sometimes along with the vertical axis of the lesion containing fibroblasts, numerous capillaries and thin elastic fibers seen usually in the dome-shaped
Periungual fibrokeratoma resembling HPV
Fig. 4. A) Scanning magnification shows hyperkeratosis, acanthosis and papillomatosis (hematoxylin/eosin); B) there is a prominent papillary appearance with hypergranulosis (hematoxylin/eosin); C) there is also hypergranulosis and perinuclear haloes (hematoxylin/eosin); D) negative staining for human papillomavirus (HPV) is illustrated.
tumors. The structure is similar to that of normal connective tissue; (ii) those with thick, closely packed collagen bundles oriented along the vertical axis of the lesion with decreased number of elastic fibers and increased number of fibroblasts. The structure is different from that of normal connective tissue and clinically seen as tall and hyperkeratotic lesions; and (iii) those presenting as flat to dome-shaped lesions that show very thin, few, irregularly arranged collagen bundles containing a few fibroblasts and lacking elastic fibers in an edematous structure with surrounding dermal edema. A hyperkeratotic stratum corneum is seen in all these three variants. In both of our cases, histopathology showed closely packed collagen bundles extending perpendicularly to the surface of the epidermis. In the stroma, the appearance of vessels, fibroblasts and thin elastic fibers was similar to those in the normal dermis. According to these findings, the histopathologic characteristics of our cases correspond to the between histopathologic type described by Kint et al. 11 In another study, Kint et al.12 investigated the histopathologic features of Koenen tumors. In this study, they also discussed whether these lesions are different from acquired digital fibrokeratoma or not. Histopathologic examination revealed capillaries surrounded by thin collagen
fibers in the distal part of the lesions and fibroblasts with fusiform nuclei among the dense, closely packed collagen fibers in the core of the lesions. There were no neural cells. The authors suggested that the histopathologic findings of these tumors resemble those of acquired digital fibrokeratoma, and they considered Koenen tumors as a particular type of fibrokeratoma. In this context, according to clinical appearance, localization and origin, the lesions can be subclassified into the following two groups: (i) acquired digital fibrokeratoma on the digits originating from the dermal connective tissue and (ii) congenital (tuberous sclerosis) or acquired fibrokeratomas originating from the proximal nail fold or the surrounding connective tissue. According to the recommendations of the International Tuberous Sclerosis Complex Consensus Conference, the presence of two or more ungual fibromas, of two or more angiomyolipomas and of lymphangioleiomyomatosis of the lung are major diagnostic criteria of tuberous sclerosis. Multiple simple renal cysts belong to the minor criteria.13 In the medical history, physical and dermatological examination of our first case showed no remarkable finding associated with tuberous sclerosis. The medical history of our second case revealed benign hepatic and pulmonary masses and renal cysts, which may
655
Göktay et al. possibly be related to tuberous sclerosis. The hepatic mass was found to be a hemangioma, and millimetric nodules in the lung were not an expected finding for tuberous sclerosis. Therefore, in our second case who has only one periungual fibrokeratoma and simple renal cysts, we think that these associations of internal findings and acquired periungual fibrokeratoma may be coincidental. Characteristic histopathologic features of HPV infection consist of hyperkeratosis, hypergranulosis, prominent keratohyaline granules, papillomatosis, acanthosis and ‘parakeratotic columns’ located on the tips of the papillomatous projections. One of the most characteristic histopathologic features of warts is koilocytes. These cells are large vacuolar keratinocytes located in the granular and malpighian layers with clear cytoplasm and small pycnotic nuclei. Eosinophilic viral inclusion bodies may be seen in the cytoplasm of these cells.14 In addition to the type 1 histopathologic findings of fibrokeratoma, we
noticed keratinocytes with binucleation and perinuclear halos considering the diagnosis of HPV infection in our cases. These findings might be associated with a primary HPV infection or secondarily infected fibrokeratomas by HPV, but HPV could not be detected by immunohistochemical analysis. In conclusion, as seen in our cases, acquired periungual fibrokeratomas arising under the proximal nail fold may show varying clinical features over time. Additionally, the multibranched clinical appearance of acquired periungual fibrokeratomas could be a more frequent finding seen in the clinical practice than reported in the literature. Finally, in the presence of histopathologic findings suggesting HPV infection such as papillomatosis, parakeratotic columns located on the top of the papillary structures, binucleation and perinuclear halos of keratinocytes, the histopathologic diagnosis of acquired periungual fibrokeratoma may be confirmed by the absence of HPV staining by immunohistochemical analysis.
References 1. Baykal C, Buyukbabani N, Yazganoglu KD, Saglik E. Acquired digital fibrokeratoma. Cutis 2007; 79: 129. 2. Haneke E. Nail surgery. Clin Dermatol 2013; 31: 516. 3. Kikuchi I, Ishii Y, Inoue S. Acquired periungual fibroma. J Dermatol 1978; 5: 235. 4. Yasuki Y. Acquired periungual fibrokeratoma – a proposal for classification of periungual fibrous lesions. J Dermatol 1985; 12: 349. 5. Moriue T, Yoneda K, Moriue J, Nakai K, Kubota Y. Multibranched acquired periungual fibrokeratoma. JAMA Dermatol 2014; 150: 456.
656
6. Saito S, Ishikawa K. Acquired periungual fibrokeratoma with accessory germinal matrix. J Hand Surg (Br) 2002; 27: 549. 7. Kumari R, Thappa DM, Devi A. Periungual acquired digital fibrokeratoma. Indian J Dermatol Venereol Leprol 2009; 75: 72. 8. Lee CY, Lee KY, Kim KH, Kim YH. Total excision of acquired periungual fibrokeratoma using bilateral proximal nail fold oblique incision for preserving nail matrix. Dermatol Surg 2010; 36: 139. 9. Mahajan D, Billings SD, Goldblum JR. Acral soft tissue tumors: a review. Adv Anat Pathol 2011; 18: 103. 10. Carlson RM, Lloyd KM, Campbell TE. Acquired periungual fibrokeratoma: a case report. Cutis 2007; 80: 137.
11. Kint A, Baran R, De Keyser H. Acquired (digital) fibrokeratoma. J Am Acad Dermatol 1985; 12: 816. 12. Kint A, Baran R. Histopathologic study of Koenen tumors. Are they different from acquired digital fibrokeratoma? J Am Acad Dermatol 1988; 18: 369. 13. Northrup H, Krueger DA, International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 2013; 49: 243. 14. Weedon D. Weedon’s skin pathology, 3rd ed. Melbourne; Elsevier, 2010pp. 608.
