146
Correspondence
Author Contributions All authors made substantial contributions to the design of the study and the acquisition of data, or analysis and interpretation thereof, assisted in drafting or revising the manuscript, and approved the final version.
Conflict of interest The authors declare that there is no conflict of interest. Steven C Smith1,* Nallasivam Palanisamy1,2,* Bryan L Betz1 Scott A Tomlins1,2,3 Rohit Mehra1,2 Lindsay A Schmidt1 David R Lucas1 Jeffrey L Myers1 1
Department of Pathology, 2Michigan Center for Translational Pathology, and 3Departments of Urology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA *These authors contributed equally to this study. 1. Thway K, Nicholson AG, Lawson K et al. Primary pulmonary myxoid sarcoma with EWSR1–CREB1 fusion: a new tumor entity. Am. J. Surg. Pathol. 2011; 35; 1722–1732. 2. Thway K, Nicholson AG, Wallace WA, Al-Nafussi A, Pilling J, Fisher C. Endobronchial pulmonary angiomatoid fibrous histiocytoma: two cases with EWSR1–CREB1 and EWSR1–ATF1 fusions. Am. J. Surg. Pathol. 2012; 36; 883–888. 3. Nicholson AG, Baandrup U, Florio R, Sheppard MN, Fisher C. Malignant myxoid endobronchial tumour: a report of two cases with a unique histological pattern. Histopathology 1999; 35; 313–318. 4. Matsukuma S, Hisaoka M, Obara K et al. Primary pulmonary myxoid sarcoma with EWSR1–CREB1 fusion, resembling extraskeletal myxoid chondrosarcoma: case report with a review of literature. Pathol. Int. 2012; 62; 817–822. 5. Chen G, Folpe AL, Colby TV et al. Angiomatoid fibrous histiocytoma: unusual sites and unusual morphology. Mod. Pathol. 2011; 24; 1560–1570. 6. Ren L, Guo SP, Zhou XG, Chan JK. Angiomatoid fibrous histiocytoma: first report of primary pulmonary origin. Am. J. Surg. Pathol. 2009; 33; 1570–1574. 7. Waters BL, Panagopoulos I, Allen EF. Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF-1 genes induced by a chromosomal translocation involving bands 12q13 and 16p11. Cancer Genet. Cytogenet. 2000; 121; 109–116. 8. Raddaoui E, Donner LR, Panagopoulos I. Fusion of the FUS and ATF1 genes in a large, deep-seated angiomatoid fibrous histiocytoma. Diagn. Mol. Pathol. 2002; 11; 157–162.
A case of oral lichen sclerosus with gingival involvement and Borrelia identification DOI: 10.1111/his.12363 © 2014 John Wiley & Sons Ltd.
Sir: Lichen sclerosus (LS) is a chronic mucocutaneous inflammatory disorder that most commonly affects the anogenital skin and occurs more frequently in females than in males.1 Clinically, it presents as white, sometimes painful, pruritic papules or plaques. Despite its predilection for the anogenital regions the condition can occur throughout the body, although lesions of the oral mucosa are exceedingly rare and those involving the gingiva are even more so.2,3 In the oral mucosa LS is seen typically in middle-aged females, the most common sites being the lower lip, buccal mucosa and upper lip.2 An increased risk of genital squamous cell carcinoma (SCC) has been documented in genital LS, thus resulting in an increased need for close follow-up and management of affected patients.1,2 Malignancy involving oral cases of LS, however, has not been reported.2 First-line treatment of LS typically involves the use of topical corticosteroids; nevertheless, the condition is not cured and remissions do not usually occur.1 Histologically, LS is characterized by an atrophic thinned epidermis with blunted rete ridges, hydropic degeneration of the basal layer, and dermal collagen sclerosis with an underlying band of lymphocytic infiltrate. These features tend to overlap in both skin and oral mucosal lesions.2,3 The underlying aetiology of LS remains unidentified; however, several possible causes have been suggested, ranging from chronic irritation to an autoimmune component, as well as infectious causes.1 Infection with Borrelia burgdorferi, the causative organism of Lyme disease, has been proposed as a possible aetiology, due to a similarity in their histological features and the identification of Borrelia organisms in some cases of LS.4 Evidence of this association has remained conflicting over the years, due in part to the overall lack of consistency in identifying Borrelia in many LS cases and in general.1,5,6 Furthermore, LS does not appear to have predominantly infectious characteristics, as there has been only a single case report of LS occurring in sexual partners.5 This does not, however, discount the possibility that LS is a reactive process occurring in Borrelia-infected skin or soft tissue. It is interesting to note that the various instances of Borrelia involvement of Histopathology, 65, 142–148.
Correspondence
147
LS have all been reported in European cases, with no previous cases reported in the United States.1 While spirochaetal forms have been observed histologically in US cases of LS, further identification of these organisms as Borrelia has not been demonstrated by serology, polymerase chain reaction (PCR), culture or immunohistochemistry.7 This regional difference may be explained by the variation in the geographical distribution of different genotypic species of Borrelia, with disease in North America associated with a single type and European cases being linked to multiple genetically distinct strains.7 This case of oral LS was found in an otherwise healthy 20-year-old male with a white 1-cm lesion on his upper labial mucosa, and an adjacent similarappearing lesion located on the maxillary gingiva in contact with the lip lesion. Both were clinically thought to be non-specific leucoplakia lesions; subsequent biopsies of both lesions with routine haematoxylin and eosin (H&E) staining demonstrated a band-like infiltrate of chronic inflammation beneath dense fibrous tissue with focal hydropic degeneration along the basement membrane and epidermal thinning, diagnostic of LS. Intradepartmental consultation was obtained for confirmation. Focus-floating microscopy (FFM), a modified immunohistochemical technique reported to be more sensitive than and almost equally specific as PCR in Borrelia detection, was subsequently performed on the specimen at the Innsbruck Medical University, Austria, as described by Eisendle et al.6,8 Figure 1 (H&E) demonstrates the affected area with epithelial atrophy, dermal collagen sclerosis with a
band-like lymphocytic infiltrate and dermal collagenization with blunted rete pegs. FFM performed on the paraffin-embedded tissue demonstrated the presence of bright red spirochaete organisms, immunohistochemically and morphologically compatible with involvement by Borrelia (Figures 2 and 3). Figure 2 outlines a spirochaete along a collagen bundle; Figure 3 shows a different focus level with a spirochaete twisting around a collagen bundle. Clinically, the patient had no significant past medical history. While the patient’s presentation with a contact lesion of the adjacent lip and gingiva is suggestive of an infectious or topical aetiology, a review
Figure 1. Biopsy demonstrating oral lichen sclerosus with epithelial atrophy and dermal collagen sclerosis with a band-like lymphocytic infiltrate (H&E).
Figure 3. Different focus level of a spirochaete, positive for Borrelia by immunohistochemistry, twisting around a collagen bundle (Focus-floating microscopy).
Histopathology, 65, 142–148.
Figure 2. Spirochaete (immunopositive for Borrelia) along a collagen bundle (Focus-floating microscopy).
148
Correspondence
of the medical record did not reveal a history of Borrelia infection and the patient had no other lesions elsewhere. A travel history to South Korea and the Middle East were noted in his record. Unfortunately, his clinical course was not available for review as he subsequently separated from military service. The typical course of LS is a lifelong chronic condition that may relapse and remit or may lead to scarring and anatomical defects, with SCC being a more ominous but less likely complication of genital LS.1 Treatment usually involves topical corticosteroids, calcineurin inhibitors, retinoids, moisturizers and long-term surveillance for the development of carcinoma.1 Antibiotics are used typically to treat associated infections that may develop; however, due to the possible role of Borrelia involvement, the question is raised as to whether antibiotics may be useful as a supplemental modality, as there are reports of LS treated with antibiotics with favourable outcomes.9 Additional clinical trials to evaluate this further may be warranted. There are approximately 27 reported cases of oral LS with histological confirmation and eight cases involving the gingiva,2 making this the 28th oral case and the ninth with gingival involvement. It also appears to be the first case of oral LS with Borrelia involvement identified by FFM reported in the United States.1,7 Despite the inconsistent historical association between LS and Borrelia involvement, there seems to be sufficient evidence that in at least some cases there is a causative or contributory relationship. This case report further adds to the evidence, and it appears that it may be worthwhile for clinicians to consider this additional aspect in the diagnosis and management of LS. Alan A George Caleb D Hixson
Steven J Peckham Donald Tyler Bernhard Zelger1 Department of Pathology, Brooke Army Medical Center, Fort Sam Houston, TX, USA, and 1Department of Dermatology and Venerology, Innsbruck Medical University, Innsbruck, Austria The designated authors above are employees of the United States Federal Government and the US Army or Air Force. The opinion(s) or assertion(s) contained herein are the private views of the author (s) and do not reflect the official policy or position of Brooke Army Medical Center, the US Army Medical Department, the US Air Force Dental Corps, the US Army Office of the Surgeon General, the Department of the Army, Department of Defense or the US government. 1. Fistarol SK, Itin PH. Diagnosis and treatment of lichen sclerosus: an update. Am. J. Clin. Dermatol. 2013; 14; 27–47. 2. Sherlin HJ, Ramalingam K, Natesan A, Ramani P, Premkumar P, Thiruvenkadam C. Lichen sclerosus of the oral cavity. Case report and review of literature. J. Dermatol. Case Rep. 2010; 3; 38–43. 3. Kim CY, Kim JG, Oh CW. Treatment of oral lichen sclerosus with 1% pimecrolimus cream. Ann. Dermatol. 2009; 22; 326– 329. 4. Aberer E, Stanek G. Histological evidence for spirochetal origin of morphea and lichen sclerosus et atrophicans. Am. J. Dermatopathol. 1987; 9; 374–379. 5. Edmonds E, Mavin S, Francis N, Ho-Yen D, Bvunker C. Borrelia burgdorferi is not associated with genital lichen sclerosus in men. Br. J. Dermatol. 2009; 160; 450–474. 6. Eisendle K, Grabner T, Kutzner H, Zelger B. Possible role of Borrelia burgdorferi sensu lato infection in lichen sclerosus. Arch. Dermatol. 2008; 144; 591–598. 7. Heymann WR, Ellis DL. Borrelia burgdorferi infections in the United States. J. Clin. Aesthet. Dermatol. 2012; 5; 18–28. 8. Eisendle K, Grabner T, Zelger B. Focus floating microscopy: ‘gold standard’ for cutaneous borreliosis? Am. J. Clin. Pathol. 2007; 127; 213–222. 9. Shelley WB, Shelley ED, Amurao CV. Treatment of lichen sclerosus with antibiotics. Int. J. Dermatol. 2006; 45; 1104– 1106.
Histopathology, 65, 142–148.
Correspondence
Author Contributions All authors made substantial contributions to the design of the study and the acquisition of data, or analysis and interpretation thereof, assisted in drafting or revising the manuscript, and approved the final version.
Conflict of interest The authors declare that there is no conflict of interest. Steven C Smith1,* Nallasivam Palanisamy1,2,* Bryan L Betz1 Scott A Tomlins1,2,3 Rohit Mehra1,2 Lindsay A Schmidt1 David R Lucas1 Jeffrey L Myers1 1
Department of Pathology, 2Michigan Center for Translational Pathology, and 3Departments of Urology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA *These authors contributed equally to this study. 1. Thway K, Nicholson AG, Lawson K et al. Primary pulmonary myxoid sarcoma with EWSR1–CREB1 fusion: a new tumor entity. Am. J. Surg. Pathol. 2011; 35; 1722–1732. 2. Thway K, Nicholson AG, Wallace WA, Al-Nafussi A, Pilling J, Fisher C. Endobronchial pulmonary angiomatoid fibrous histiocytoma: two cases with EWSR1–CREB1 and EWSR1–ATF1 fusions. Am. J. Surg. Pathol. 2012; 36; 883–888. 3. Nicholson AG, Baandrup U, Florio R, Sheppard MN, Fisher C. Malignant myxoid endobronchial tumour: a report of two cases with a unique histological pattern. Histopathology 1999; 35; 313–318. 4. Matsukuma S, Hisaoka M, Obara K et al. Primary pulmonary myxoid sarcoma with EWSR1–CREB1 fusion, resembling extraskeletal myxoid chondrosarcoma: case report with a review of literature. Pathol. Int. 2012; 62; 817–822. 5. Chen G, Folpe AL, Colby TV et al. Angiomatoid fibrous histiocytoma: unusual sites and unusual morphology. Mod. Pathol. 2011; 24; 1560–1570. 6. Ren L, Guo SP, Zhou XG, Chan JK. Angiomatoid fibrous histiocytoma: first report of primary pulmonary origin. Am. J. Surg. Pathol. 2009; 33; 1570–1574. 7. Waters BL, Panagopoulos I, Allen EF. Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF-1 genes induced by a chromosomal translocation involving bands 12q13 and 16p11. Cancer Genet. Cytogenet. 2000; 121; 109–116. 8. Raddaoui E, Donner LR, Panagopoulos I. Fusion of the FUS and ATF1 genes in a large, deep-seated angiomatoid fibrous histiocytoma. Diagn. Mol. Pathol. 2002; 11; 157–162.
A case of oral lichen sclerosus with gingival involvement and Borrelia identification DOI: 10.1111/his.12363 © 2014 John Wiley & Sons Ltd.
Sir: Lichen sclerosus (LS) is a chronic mucocutaneous inflammatory disorder that most commonly affects the anogenital skin and occurs more frequently in females than in males.1 Clinically, it presents as white, sometimes painful, pruritic papules or plaques. Despite its predilection for the anogenital regions the condition can occur throughout the body, although lesions of the oral mucosa are exceedingly rare and those involving the gingiva are even more so.2,3 In the oral mucosa LS is seen typically in middle-aged females, the most common sites being the lower lip, buccal mucosa and upper lip.2 An increased risk of genital squamous cell carcinoma (SCC) has been documented in genital LS, thus resulting in an increased need for close follow-up and management of affected patients.1,2 Malignancy involving oral cases of LS, however, has not been reported.2 First-line treatment of LS typically involves the use of topical corticosteroids; nevertheless, the condition is not cured and remissions do not usually occur.1 Histologically, LS is characterized by an atrophic thinned epidermis with blunted rete ridges, hydropic degeneration of the basal layer, and dermal collagen sclerosis with an underlying band of lymphocytic infiltrate. These features tend to overlap in both skin and oral mucosal lesions.2,3 The underlying aetiology of LS remains unidentified; however, several possible causes have been suggested, ranging from chronic irritation to an autoimmune component, as well as infectious causes.1 Infection with Borrelia burgdorferi, the causative organism of Lyme disease, has been proposed as a possible aetiology, due to a similarity in their histological features and the identification of Borrelia organisms in some cases of LS.4 Evidence of this association has remained conflicting over the years, due in part to the overall lack of consistency in identifying Borrelia in many LS cases and in general.1,5,6 Furthermore, LS does not appear to have predominantly infectious characteristics, as there has been only a single case report of LS occurring in sexual partners.5 This does not, however, discount the possibility that LS is a reactive process occurring in Borrelia-infected skin or soft tissue. It is interesting to note that the various instances of Borrelia involvement of Histopathology, 65, 142–148.
Correspondence
147
LS have all been reported in European cases, with no previous cases reported in the United States.1 While spirochaetal forms have been observed histologically in US cases of LS, further identification of these organisms as Borrelia has not been demonstrated by serology, polymerase chain reaction (PCR), culture or immunohistochemistry.7 This regional difference may be explained by the variation in the geographical distribution of different genotypic species of Borrelia, with disease in North America associated with a single type and European cases being linked to multiple genetically distinct strains.7 This case of oral LS was found in an otherwise healthy 20-year-old male with a white 1-cm lesion on his upper labial mucosa, and an adjacent similarappearing lesion located on the maxillary gingiva in contact with the lip lesion. Both were clinically thought to be non-specific leucoplakia lesions; subsequent biopsies of both lesions with routine haematoxylin and eosin (H&E) staining demonstrated a band-like infiltrate of chronic inflammation beneath dense fibrous tissue with focal hydropic degeneration along the basement membrane and epidermal thinning, diagnostic of LS. Intradepartmental consultation was obtained for confirmation. Focus-floating microscopy (FFM), a modified immunohistochemical technique reported to be more sensitive than and almost equally specific as PCR in Borrelia detection, was subsequently performed on the specimen at the Innsbruck Medical University, Austria, as described by Eisendle et al.6,8 Figure 1 (H&E) demonstrates the affected area with epithelial atrophy, dermal collagen sclerosis with a
band-like lymphocytic infiltrate and dermal collagenization with blunted rete pegs. FFM performed on the paraffin-embedded tissue demonstrated the presence of bright red spirochaete organisms, immunohistochemically and morphologically compatible with involvement by Borrelia (Figures 2 and 3). Figure 2 outlines a spirochaete along a collagen bundle; Figure 3 shows a different focus level with a spirochaete twisting around a collagen bundle. Clinically, the patient had no significant past medical history. While the patient’s presentation with a contact lesion of the adjacent lip and gingiva is suggestive of an infectious or topical aetiology, a review
Figure 1. Biopsy demonstrating oral lichen sclerosus with epithelial atrophy and dermal collagen sclerosis with a band-like lymphocytic infiltrate (H&E).
Figure 3. Different focus level of a spirochaete, positive for Borrelia by immunohistochemistry, twisting around a collagen bundle (Focus-floating microscopy).
Histopathology, 65, 142–148.
Figure 2. Spirochaete (immunopositive for Borrelia) along a collagen bundle (Focus-floating microscopy).
148
Correspondence
of the medical record did not reveal a history of Borrelia infection and the patient had no other lesions elsewhere. A travel history to South Korea and the Middle East were noted in his record. Unfortunately, his clinical course was not available for review as he subsequently separated from military service. The typical course of LS is a lifelong chronic condition that may relapse and remit or may lead to scarring and anatomical defects, with SCC being a more ominous but less likely complication of genital LS.1 Treatment usually involves topical corticosteroids, calcineurin inhibitors, retinoids, moisturizers and long-term surveillance for the development of carcinoma.1 Antibiotics are used typically to treat associated infections that may develop; however, due to the possible role of Borrelia involvement, the question is raised as to whether antibiotics may be useful as a supplemental modality, as there are reports of LS treated with antibiotics with favourable outcomes.9 Additional clinical trials to evaluate this further may be warranted. There are approximately 27 reported cases of oral LS with histological confirmation and eight cases involving the gingiva,2 making this the 28th oral case and the ninth with gingival involvement. It also appears to be the first case of oral LS with Borrelia involvement identified by FFM reported in the United States.1,7 Despite the inconsistent historical association between LS and Borrelia involvement, there seems to be sufficient evidence that in at least some cases there is a causative or contributory relationship. This case report further adds to the evidence, and it appears that it may be worthwhile for clinicians to consider this additional aspect in the diagnosis and management of LS. Alan A George Caleb D Hixson
Steven J Peckham Donald Tyler Bernhard Zelger1 Department of Pathology, Brooke Army Medical Center, Fort Sam Houston, TX, USA, and 1Department of Dermatology and Venerology, Innsbruck Medical University, Innsbruck, Austria The designated authors above are employees of the United States Federal Government and the US Army or Air Force. The opinion(s) or assertion(s) contained herein are the private views of the author (s) and do not reflect the official policy or position of Brooke Army Medical Center, the US Army Medical Department, the US Air Force Dental Corps, the US Army Office of the Surgeon General, the Department of the Army, Department of Defense or the US government. 1. Fistarol SK, Itin PH. Diagnosis and treatment of lichen sclerosus: an update. Am. J. Clin. Dermatol. 2013; 14; 27–47. 2. Sherlin HJ, Ramalingam K, Natesan A, Ramani P, Premkumar P, Thiruvenkadam C. Lichen sclerosus of the oral cavity. Case report and review of literature. J. Dermatol. Case Rep. 2010; 3; 38–43. 3. Kim CY, Kim JG, Oh CW. Treatment of oral lichen sclerosus with 1% pimecrolimus cream. Ann. Dermatol. 2009; 22; 326– 329. 4. Aberer E, Stanek G. Histological evidence for spirochetal origin of morphea and lichen sclerosus et atrophicans. Am. J. Dermatopathol. 1987; 9; 374–379. 5. Edmonds E, Mavin S, Francis N, Ho-Yen D, Bvunker C. Borrelia burgdorferi is not associated with genital lichen sclerosus in men. Br. J. Dermatol. 2009; 160; 450–474. 6. Eisendle K, Grabner T, Kutzner H, Zelger B. Possible role of Borrelia burgdorferi sensu lato infection in lichen sclerosus. Arch. Dermatol. 2008; 144; 591–598. 7. Heymann WR, Ellis DL. Borrelia burgdorferi infections in the United States. J. Clin. Aesthet. Dermatol. 2012; 5; 18–28. 8. Eisendle K, Grabner T, Zelger B. Focus floating microscopy: ‘gold standard’ for cutaneous borreliosis? Am. J. Clin. Pathol. 2007; 127; 213–222. 9. Shelley WB, Shelley ED, Amurao CV. Treatment of lichen sclerosus with antibiotics. Int. J. Dermatol. 2006; 45; 1104– 1106.
Histopathology, 65, 142–148.
