Cutis

Perineurial cells, present in both myelinated and unmyelinated nerves, make up the external sheath, referred to as the perineurium, which acts as a perifascicular diffusion barrier for peripheral nerves.1 Perineuriomas are rare slow-growing tumors composed exclusively of perineurial cells that develop in the dermis, subcutis, or deep soft tissue. Diagnosis relies on the identification of the distinct characteristics of the perineurial cells that compose this tumor. Perineuriomas can arise in various locations and may exhibit several different histologic patterns, all sharing a consistent immunohistochemical and ultrastructural makeup. Familiarity with this entity should help to avoid confusion with more common lesions presenting on a digit, such as a giant cell tumor of the tendon sheath, fibroma of the tendon sheath, neurilemoma, neurofibroma, or sclerotic fibroma. We report 2 cases of soft tissue perineurioma presenting on a digit.

Case Reports

Patient 1—A 13-year-old girl presented with a large, asymptomatic, smooth-surfaced, rubbery-firm reddish yellow nodule on the dorsal mid phalanx of the right third finger that had remained unchanged for 7 years (Figure 1). There was no history of ulceration, infection, or trauma to the area. Results of an x-ray of the right hand revealed soft tissue swelling over the second phalanx with no periosteal reaction.

Results of a biopsy revealed a poorly marginated storiform spindle cell neoplasm involving the dermis and subcutaneous tissue. The base of the proliferation was sharply demarcated centrally, with areas of diffuse infiltration of the adipose tissue peripherally. The spindle cells were uniformly arranged in interweaving fascicles, with portions in a storiform configuration (Figures 2 and 3). Results of immunostains were positive for vimentin and epithelial membrane antigen (EMA) and negative for S-100, HMB-45, melan-A, and desmin (Figure 4). The entire nodule was later removed by an orthopedic surgeon. At 14-month follow-up, the patient reported no evidence of recurrence and a fully functional finger.

Patient 2—A 54-year-old woman with no significant medical history presented with a 4-mm, asymptomatic, firm, skin-colored, smooth-surfaced papule on the dorsal distal phalanx of the left fifth finger. The lesion had been present for 3 to 4 years with no change in appearance. A shave specimen of the exophytic portion of the lesion revealed a fibrotic base that could not be removed with light curettage. Results of histologic evaluation revealed a dome-shaped dermal fibrotic nodule extending to the deep margin of excision. Within the dermis, there was increased deposition of collagen with a proliferation of spindle cells arranged in short fascicles with an ill-defined border. Within the proliferation were foci of cells arranged in a concentric pattern with portions mimicking the appearance of a sclerotic fibroma. No atypia was noted. Results of immunostains were positive for EMA, weakly positive for factor XIIIa, and negative for S-100 and HMB-45. The entire lesion was later removed by a plastic surgeon. 

Comment Perineuriomas result from a proliferation of perineurial cells that normally form the external sheath at the interface between epineurial and endoneurial tissues. These cells have distinct ultrastructural and immunohistochemical phenotypes that comprise a unique component of the normal perineurium. The key diagnostic features include immunoreactivity for EMA with lack of reactivity for S-100. Results of staining for laminin and collagen IV are positive, which can reinforce evidence for perineurial cell differentiation. There are variable staining results for factor XIIIa and CD34,2 whereas results for cytokeratin and desmin are negative. Ultrastructural features, which may be helpful in confirming the diagnosis, include a discontinuous external lamina, junctional complexes, occasional pinocytotic vesicles, and elongated and spindled cell processes.3 Identification of a bland spindle cell proliferation on hematoxylin-eosin (H&E) staining, along with the distinct staining profile, form the basis of diagnosing a perineurioma. Although perineuriomas were originally described by Lazarus and Trombetta in 1978,4 it was not until the 1999 international consensus conference of neuropathologists that the World Health Organization officially included the perineurioma in its published classification of nervous system tumors.5 Perineuriomas are rare, invariably benign, peripheral nerve sheath neoplasms with 3 distinct variants established to date: intraneural and extraneural variants, and the more recently described sclerosing perineurioma.6 The intraneural type extends directly from a peripheral nerve and exhibits a distinct pseudo–onion bulb morphology.5 The most common presentation is on the extremities of young adults, where it produces a fusiform expansion of the affected nerve. It has been suggested that this may actually represent a reactive process of nerve degeneration rather than a benign free-standing entity.3 The extraneural variant, most commonly referred to as soft tissue perineuriomas, lack association with an identifiable nerve. This type most closely resembles the original report by Lazarus and Trombetta, subsequently reported in the literature as storiform perineurial fibromas.7,8 Soft tissue perineuriomas usually present in middle-aged women (female-male ratio, 4:1), with a predilection for the subcutaneous tissue of the extremities or trunk.5 Several reports describe presentation on digits, with rare cases describing nail apparatus involvment.1,9,10 Histologically, the tumors exhibit varied cellularity composed of elongated and spindled cells with a loose storiform, short fascicular, whorled growth pattern. The sclerosing perineurioma is a recently established variant showing predilection for the digits and palms. Although there is a morphologic overlap with the other forms of perineurioma, the sclerotic variant features plumper, more epithelioid perineurial cells, forming cords and trabecular arrangements embedded in a dense collagen stroma.3,11 Although not classic, many of these sclerotic features overlap with those of our second case, demonstrating the condition's rich tapestry of presentation. Although each type shows differences in clinical and gross characteristics, all share immunohistochemical and ultrastructural features typical of perineurial cells.5 The original case of perineurioma was described on the basis of its ultrastructure; however, distinct immunohistochemical markers that differentiate the perineurioma from more common tumors encountered on a digit are used today. Importantly, immunostains reveal cells to be negative for S-100, differentiating the perineurial cell from the Schwann cell, which is positive for S-100 and negative for EMA. Both the neurilemoma and the neurofibroma show reactivity for S-100. The diagnosis of giant cell tumor of the tendon sheath is usually characterized by the presence of osteoclastlike giant cells, but these markers may be subtle or entirely absent. The absence of EMA activity, also lacking in fibroma of the tendon sheath, helps to differentiate giant cell tumor of the tendon sheath from perineurioma in this scenario.1 A calcifying aponeurotic fibroma also could potentially be confused with a perineurioma, but the absence of cartilage or calcification, and reactivity for vimentin only, would differentiate the 2 entities.1 Multiple sclerotic fibromas may serve as a cutaneous marker for Cowden disease. These well-demarcated dermal nodules with thick hyalinized collagen bundles with a storiform and whorled architecture may be confused with the perineurioma, especially those of the sclerotic variant. The sclerotic fibromas of Cowden disease, though positive for factor XIIIa and collagen IV, are negative for laminin and EMA. Because EMA expression is a key to the diagnosis of perineurioma, and because at times the reactivity may be focal or faint, additional markers specific to perineurial cells are of particular interest. In a recent report on a group of tight junction-associated proteins, it was noted that perineurial cells expressed high levels of claudin-1. Folpe et al12 showed expression of claudin-1 in 11 of 12 cases of perineurioma, of which the majority showed a higher reactivity for claudin-1 staining compared with the corresponding EMA stain. Importantly, claudin-1 is not expressed in the mesenchymal tumors that may enter into the differential diagnosis of perineurioma. Claudin-1 may serve as a valuable adjunct to EMA in cases with less than classic characteristics. Several reports have described genetic abnormalities that serve as a common denominator within the perineurioma spectrum. Giannini et al7 postulated that soft tissue perineurioma exhibited the same chromosome 22 abnormalities found in intraneural variants. The researchers conducted a fluorescent in situ hybridization experiment with a probe specific for the M-BCR locus, which maps chromosome band 22q11, and found that 4 out of 5 cases tested showed deletion of part of chromosome 22.7 Recently, similar abnormalities were found in the sclerosing variant. Sciot et al,13 using 2 markers for the 5'BCR and the NF2 loci, both on chromosome 22, showed cryptic deletion of these loci, further supporting that a gene on chromosome 22 may play a role in the pathogenesis of perineurioma. Because of its involvement in other nerve sheath tumors, the NF2 gene is a logical candidate. Excision with a thin margin of normal tissue is curative. Due to the nonspecific clinical appearance and varying histologic morphology, the perineurioma is likely to be confused with more common tumors of the hand. Further investigation is needed to learn more about new variants of perineurioma, more specific immunostains for use in diagnosis, and identification of specific genes that are a key to the condition's pathogenesis. Perineurioma joins the more commonly recognized giant cell tumor of the tendon sheath, fibroma of the tendon sheath, neurilemoma, neurofibroma as a soft tissue tumor, and sclerosing fibroma that may present on a digit.

Perineurial cells, present in both myelinated and unmyelinated nerves, make up the external sheath, referred to as the perineurium, which acts as a perifascicular diffusion barrier for peripheral nerves.1 Perineuriomas are rare slow-growing tumors composed exclusively of perineurial cells that develop in the dermis, subcutis, or deep soft tissue. Diagnosis relies on the identification of the distinct characteristics of the perineurial cells that compose this tumor. Perineuriomas can arise in various locations and may exhibit several different histologic patterns, all sharing a consistent immunohistochemical and ultrastructural makeup. Familiarity with this entity should help to avoid confusion with more common lesions presenting on a digit, such as a giant cell tumor of the tendon sheath, fibroma of the tendon sheath, neurilemoma, neurofibroma, or sclerotic fibroma. We report 2 cases of soft tissue perineurioma presenting on a digit.

Case Reports

Patient 1—A 13-year-old girl presented with a large, asymptomatic, smooth-surfaced, rubbery-firm reddish yellow nodule on the dorsal mid phalanx of the right third finger that had remained unchanged for 7 years (Figure 1). There was no history of ulceration, infection, or trauma to the area. Results of an x-ray of the right hand revealed soft tissue swelling over the second phalanx with no periosteal reaction.

Results of a biopsy revealed a poorly marginated storiform spindle cell neoplasm involving the dermis and subcutaneous tissue. The base of the proliferation was sharply demarcated centrally, with areas of diffuse infiltration of the adipose tissue peripherally. The spindle cells were uniformly arranged in interweaving fascicles, with portions in a storiform configuration (Figures 2 and 3). Results of immunostains were positive for vimentin and epithelial membrane antigen (EMA) and negative for S-100, HMB-45, melan-A, and desmin (Figure 4). The entire nodule was later removed by an orthopedic surgeon. At 14-month follow-up, the patient reported no evidence of recurrence and a fully functional finger.

Patient 2—A 54-year-old woman with no significant medical history presented with a 4-mm, asymptomatic, firm, skin-colored, smooth-surfaced papule on the dorsal distal phalanx of the left fifth finger. The lesion had been present for 3 to 4 years with no change in appearance. A shave specimen of the exophytic portion of the lesion revealed a fibrotic base that could not be removed with light curettage. Results of histologic evaluation revealed a dome-shaped dermal fibrotic nodule extending to the deep margin of excision. Within the dermis, there was increased deposition of collagen with a proliferation of spindle cells arranged in short fascicles with an ill-defined border. Within the proliferation were foci of cells arranged in a concentric pattern with portions mimicking the appearance of a sclerotic fibroma. No atypia was noted. Results of immunostains were positive for EMA, weakly positive for factor XIIIa, and negative for S-100 and HMB-45. The entire lesion was later removed by a plastic surgeon. 

Comment Perineuriomas result from a proliferation of perineurial cells that normally form the external sheath at the interface between epineurial and endoneurial tissues. These cells have distinct ultrastructural and immunohistochemical phenotypes that comprise a unique component of the normal perineurium. The key diagnostic features include immunoreactivity for EMA with lack of reactivity for S-100. Results of staining for laminin and collagen IV are positive, which can reinforce evidence for perineurial cell differentiation. There are variable staining results for factor XIIIa and CD34,2 whereas results for cytokeratin and desmin are negative. Ultrastructural features, which may be helpful in confirming the diagnosis, include a discontinuous external lamina, junctional complexes, occasional pinocytotic vesicles, and elongated and spindled cell processes.3 Identification of a bland spindle cell proliferation on hematoxylin-eosin (H&E) staining, along with the distinct staining profile, form the basis of diagnosing a perineurioma. Although perineuriomas were originally described by Lazarus and Trombetta in 1978,4 it was not until the 1999 international consensus conference of neuropathologists that the World Health Organization officially included the perineurioma in its published classification of nervous system tumors.5 Perineuriomas are rare, invariably benign, peripheral nerve sheath neoplasms with 3 distinct variants established to date: intraneural and extraneural variants, and the more recently described sclerosing perineurioma.6 The intraneural type extends directly from a peripheral nerve and exhibits a distinct pseudo–onion bulb morphology.5 The most common presentation is on the extremities of young adults, where it produces a fusiform expansion of the affected nerve. It has been suggested that this may actually represent a reactive process of nerve degeneration rather than a benign free-standing entity.3 The extraneural variant, most commonly referred to as soft tissue perineuriomas, lack association with an identifiable nerve. This type most closely resembles the original report by Lazarus and Trombetta, subsequently reported in the literature as storiform perineurial fibromas.7,8 Soft tissue perineuriomas usually present in middle-aged women (female-male ratio, 4:1), with a predilection for the subcutaneous tissue of the extremities or trunk.5 Several reports describe presentation on digits, with rare cases describing nail apparatus involvment.1,9,10 Histologically, the tumors exhibit varied cellularity composed of elongated and spindled cells with a loose storiform, short fascicular, whorled growth pattern. The sclerosing perineurioma is a recently established variant showing predilection for the digits and palms. Although there is a morphologic overlap with the other forms of perineurioma, the sclerotic variant features plumper, more epithelioid perineurial cells, forming cords and trabecular arrangements embedded in a dense collagen stroma.3,11 Although not classic, many of these sclerotic features overlap with those of our second case, demonstrating the condition's rich tapestry of presentation. Although each type shows differences in clinical and gross characteristics, all share immunohistochemical and ultrastructural features typical of perineurial cells.5 The original case of perineurioma was described on the basis of its ultrastructure; however, distinct immunohistochemical markers that differentiate the perineurioma from more common tumors encountered on a digit are used today. Importantly, immunostains reveal cells to be negative for S-100, differentiating the perineurial cell from the Schwann cell, which is positive for S-100 and negative for EMA. Both the neurilemoma and the neurofibroma show reactivity for S-100. The diagnosis of giant cell tumor of the tendon sheath is usually characterized by the presence of osteoclastlike giant cells, but these markers may be subtle or entirely absent. The absence of EMA activity, also lacking in fibroma of the tendon sheath, helps to differentiate giant cell tumor of the tendon sheath from perineurioma in this scenario.1 A calcifying aponeurotic fibroma also could potentially be confused with a perineurioma, but the absence of cartilage or calcification, and reactivity for vimentin only, would differentiate the 2 entities.1 Multiple sclerotic fibromas may serve as a cutaneous marker for Cowden disease. These well-demarcated dermal nodules with thick hyalinized collagen bundles with a storiform and whorled architecture may be confused with the perineurioma, especially those of the sclerotic variant. The sclerotic fibromas of Cowden disease, though positive for factor XIIIa and collagen IV, are negative for laminin and EMA. Because EMA expression is a key to the diagnosis of perineurioma, and because at times the reactivity may be focal or faint, additional markers specific to perineurial cells are of particular interest. In a recent report on a group of tight junction-associated proteins, it was noted that perineurial cells expressed high levels of claudin-1. Folpe et al12 showed expression of claudin-1 in 11 of 12 cases of perineurioma, of which the majority showed a higher reactivity for claudin-1 staining compared with the corresponding EMA stain. Importantly, claudin-1 is not expressed in the mesenchymal tumors that may enter into the differential diagnosis of perineurioma. Claudin-1 may serve as a valuable adjunct to EMA in cases with less than classic characteristics. Several reports have described genetic abnormalities that serve as a common denominator within the perineurioma spectrum. Giannini et al7 postulated that soft tissue perineurioma exhibited the same chromosome 22 abnormalities found in intraneural variants. The researchers conducted a fluorescent in situ hybridization experiment with a probe specific for the M-BCR locus, which maps chromosome band 22q11, and found that 4 out of 5 cases tested showed deletion of part of chromosome 22.7 Recently, similar abnormalities were found in the sclerosing variant. Sciot et al,13 using 2 markers for the 5'BCR and the NF2 loci, both on chromosome 22, showed cryptic deletion of these loci, further supporting that a gene on chromosome 22 may play a role in the pathogenesis of perineurioma. Because of its involvement in other nerve sheath tumors, the NF2 gene is a logical candidate. Excision with a thin margin of normal tissue is curative. Due to the nonspecific clinical appearance and varying histologic morphology, the perineurioma is likely to be confused with more common tumors of the hand. Further investigation is needed to learn more about new variants of perineurioma, more specific immunostains for use in diagnosis, and identification of specific genes that are a key to the condition's pathogenesis. Perineurioma joins the more commonly recognized giant cell tumor of the tendon sheath, fibroma of the tendon sheath, neurilemoma, neurofibroma as a soft tissue tumor, and sclerosing fibroma that may present on a digit.

Perineurial cells, present in both myelinated and unmyelinated nerves, make up the external sheath, referred to as the perineurium, which acts as a perifascicular diffusion barrier for peripheral nerves.1 Perineuriomas are rare slow-growing tumors composed exclusively of perineurial cells that develop in the dermis, subcutis, or deep soft tissue. Diagnosis relies on the identification of the distinct characteristics of the perineurial cells that compose this tumor. Perineuriomas can arise in various locations and may exhibit several different histologic patterns, all sharing a consistent immunohistochemical and ultrastructural makeup. Familiarity with this entity should help to avoid confusion with more common lesions presenting on a digit, such as a giant cell tumor of the tendon sheath, fibroma of the tendon sheath, neurilemoma, neurofibroma, or sclerotic fibroma. We report 2 cases of soft tissue perineurioma presenting on a digit.

Case Reports

Patient 1—A 13-year-old girl presented with a large, asymptomatic, smooth-surfaced, rubbery-firm reddish yellow nodule on the dorsal mid phalanx of the right third finger that had remained unchanged for 7 years (Figure 1). There was no history of ulceration, infection, or trauma to the area. Results of an x-ray of the right hand revealed soft tissue swelling over the second phalanx with no periosteal reaction.

Results of a biopsy revealed a poorly marginated storiform spindle cell neoplasm involving the dermis and subcutaneous tissue. The base of the proliferation was sharply demarcated centrally, with areas of diffuse infiltration of the adipose tissue peripherally. The spindle cells were uniformly arranged in interweaving fascicles, with portions in a storiform configuration (Figures 2 and 3). Results of immunostains were positive for vimentin and epithelial membrane antigen (EMA) and negative for S-100, HMB-45, melan-A, and desmin (Figure 4). The entire nodule was later removed by an orthopedic surgeon. At 14-month follow-up, the patient reported no evidence of recurrence and a fully functional finger.

Patient 2—A 54-year-old woman with no significant medical history presented with a 4-mm, asymptomatic, firm, skin-colored, smooth-surfaced papule on the dorsal distal phalanx of the left fifth finger. The lesion had been present for 3 to 4 years with no change in appearance. A shave specimen of the exophytic portion of the lesion revealed a fibrotic base that could not be removed with light curettage. Results of histologic evaluation revealed a dome-shaped dermal fibrotic nodule extending to the deep margin of excision. Within the dermis, there was increased deposition of collagen with a proliferation of spindle cells arranged in short fascicles with an ill-defined border. Within the proliferation were foci of cells arranged in a concentric pattern with portions mimicking the appearance of a sclerotic fibroma. No atypia was noted. Results of immunostains were positive for EMA, weakly positive for factor XIIIa, and negative for S-100 and HMB-45. The entire lesion was later removed by a plastic surgeon. 

Comment Perineuriomas result from a proliferation of perineurial cells that normally form the external sheath at the interface between epineurial and endoneurial tissues. These cells have distinct ultrastructural and immunohistochemical phenotypes that comprise a unique component of the normal perineurium. The key diagnostic features include immunoreactivity for EMA with lack of reactivity for S-100. Results of staining for laminin and collagen IV are positive, which can reinforce evidence for perineurial cell differentiation. There are variable staining results for factor XIIIa and CD34,2 whereas results for cytokeratin and desmin are negative. Ultrastructural features, which may be helpful in confirming the diagnosis, include a discontinuous external lamina, junctional complexes, occasional pinocytotic vesicles, and elongated and spindled cell processes.3 Identification of a bland spindle cell proliferation on hematoxylin-eosin (H&E) staining, along with the distinct staining profile, form the basis of diagnosing a perineurioma. Although perineuriomas were originally described by Lazarus and Trombetta in 1978,4 it was not until the 1999 international consensus conference of neuropathologists that the World Health Organization officially included the perineurioma in its published classification of nervous system tumors.5 Perineuriomas are rare, invariably benign, peripheral nerve sheath neoplasms with 3 distinct variants established to date: intraneural and extraneural variants, and the more recently described sclerosing perineurioma.6 The intraneural type extends directly from a peripheral nerve and exhibits a distinct pseudo–onion bulb morphology.5 The most common presentation is on the extremities of young adults, where it produces a fusiform expansion of the affected nerve. It has been suggested that this may actually represent a reactive process of nerve degeneration rather than a benign free-standing entity.3 The extraneural variant, most commonly referred to as soft tissue perineuriomas, lack association with an identifiable nerve. This type most closely resembles the original report by Lazarus and Trombetta, subsequently reported in the literature as storiform perineurial fibromas.7,8 Soft tissue perineuriomas usually present in middle-aged women (female-male ratio, 4:1), with a predilection for the subcutaneous tissue of the extremities or trunk.5 Several reports describe presentation on digits, with rare cases describing nail apparatus involvment.1,9,10 Histologically, the tumors exhibit varied cellularity composed of elongated and spindled cells with a loose storiform, short fascicular, whorled growth pattern. The sclerosing perineurioma is a recently established variant showing predilection for the digits and palms. Although there is a morphologic overlap with the other forms of perineurioma, the sclerotic variant features plumper, more epithelioid perineurial cells, forming cords and trabecular arrangements embedded in a dense collagen stroma.3,11 Although not classic, many of these sclerotic features overlap with those of our second case, demonstrating the condition's rich tapestry of presentation. Although each type shows differences in clinical and gross characteristics, all share immunohistochemical and ultrastructural features typical of perineurial cells.5 The original case of perineurioma was described on the basis of its ultrastructure; however, distinct immunohistochemical markers that differentiate the perineurioma from more common tumors encountered on a digit are used today. Importantly, immunostains reveal cells to be negative for S-100, differentiating the perineurial cell from the Schwann cell, which is positive for S-100 and negative for EMA. Both the neurilemoma and the neurofibroma show reactivity for S-100. The diagnosis of giant cell tumor of the tendon sheath is usually characterized by the presence of osteoclastlike giant cells, but these markers may be subtle or entirely absent. The absence of EMA activity, also lacking in fibroma of the tendon sheath, helps to differentiate giant cell tumor of the tendon sheath from perineurioma in this scenario.1 A calcifying aponeurotic fibroma also could potentially be confused with a perineurioma, but the absence of cartilage or calcification, and reactivity for vimentin only, would differentiate the 2 entities.1 Multiple sclerotic fibromas may serve as a cutaneous marker for Cowden disease. These well-demarcated dermal nodules with thick hyalinized collagen bundles with a storiform and whorled architecture may be confused with the perineurioma, especially those of the sclerotic variant. The sclerotic fibromas of Cowden disease, though positive for factor XIIIa and collagen IV, are negative for laminin and EMA. Because EMA expression is a key to the diagnosis of perineurioma, and because at times the reactivity may be focal or faint, additional markers specific to perineurial cells are of particular interest. In a recent report on a group of tight junction-associated proteins, it was noted that perineurial cells expressed high levels of claudin-1. Folpe et al12 showed expression of claudin-1 in 11 of 12 cases of perineurioma, of which the majority showed a higher reactivity for claudin-1 staining compared with the corresponding EMA stain. Importantly, claudin-1 is not expressed in the mesenchymal tumors that may enter into the differential diagnosis of perineurioma. Claudin-1 may serve as a valuable adjunct to EMA in cases with less than classic characteristics. Several reports have described genetic abnormalities that serve as a common denominator within the perineurioma spectrum. Giannini et al7 postulated that soft tissue perineurioma exhibited the same chromosome 22 abnormalities found in intraneural variants. The researchers conducted a fluorescent in situ hybridization experiment with a probe specific for the M-BCR locus, which maps chromosome band 22q11, and found that 4 out of 5 cases tested showed deletion of part of chromosome 22.7 Recently, similar abnormalities were found in the sclerosing variant. Sciot et al,13 using 2 markers for the 5'BCR and the NF2 loci, both on chromosome 22, showed cryptic deletion of these loci, further supporting that a gene on chromosome 22 may play a role in the pathogenesis of perineurioma. Because of its involvement in other nerve sheath tumors, the NF2 gene is a logical candidate. Excision with a thin margin of normal tissue is curative. Due to the nonspecific clinical appearance and varying histologic morphology, the perineurioma is likely to be confused with more common tumors of the hand. Further investigation is needed to learn more about new variants of perineurioma, more specific immunostains for use in diagnosis, and identification of specific genes that are a key to the condition's pathogenesis. Perineurioma joins the more commonly recognized giant cell tumor of the tendon sheath, fibroma of the tendon sheath, neurilemoma, neurofibroma as a soft tissue tumor, and sclerosing fibroma that may present on a digit.

Case Report

A 35-year-old white man visited our Sector of Dermatology complaining about a feeling of increased weight and volume in his arms and legs that had started 2 months previously. The symptoms had begun 48 hours after a vigorous and unusual physical effort—carrying 30- to 40-kg boxes during a more than 2.5-hour period. When the patient sought medical assistance, his problem was diagnosed as rheumatism. He was prescribed a nonsteroidal anti-inflammatory drug, with partial improvement. A few days later, his condition evolved to hand and wrist joint induration lasting more than 2 hours that was associated with a discrete disturbance to his normal way of walking.

The patient did not exercise regularly and denied the use of medication containing L-tryptophan. He did not report any systemic signs and symptoms such as fever, reduced weight, hyporexia, dyspnea, difficulty swallowing solids and liquids, previous upper respiratory tract infections, recent history of hepatitis, diabetes mellitus, or similar cases in the family.

Results of a physical examination showed loss of weight and skin blushing. The patient was hydrated, acyanotic, anicteric, feverless, and eupneic. His arterial pressure was 120x80 mm Hg, with ample peripheral pulses. The patient showed atypical facies without edema, with normal wrinkling for his gender and age and a mouth opening of 4.5 cm. His thorax and abdomen were without abnormalities. His upper and lower limbs had increased volume with infiltration varying from discrete to moderate, without sustained depressions at finger pressure except on the extremities. There was absence of Raynaud phenomenon. Results of an examination of articulations showed absence of edema or synovitis of the knees, ankles, wrists, and hands; mobility was free and painless.

Results of a dermatologic examination revealed visible sclerosis of limb skin, which was more evident at the extremities and diminished in intensity in the direction of the proximal region; in addition, the affected area had a discrete yellowish color, scarcity of hair, and telangiectasia (Figures 1 and 2).

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Results of laboratory tests showed intense eosinophilia (28%: a blood count of 2500 eosinophils in 8900 leukocytes); an increased erythrocyte sedimentation rate; and hypergammaglobulinemia (35.7%). His immunologic profile was evaluated for antinuclear factor, anti-DNA, antitopoisomerase, and anticentromere antibodies; all test results were negative. Antibodies for human immunodeficiency virus and indicators for hepatitis also were negative. Urine sediment and parasitologic stool examinations, as well as an x-ray of the thorax, did not reveal alterations. An incisional biopsy down to the muscular fascia was performed with a scalpel on the anterior surface of the right forearm.

Results of a histopathologic examination with hematoxylin-eosin stain revealed an inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils around dermal vessels, mostly at the muscular fascia and adjacent adipose tissue (Figures 3 and 4). Results of direct immunofluorescence showed immunoreactivity to fibrinogen in some vessels of the superficial dermis; however, the results were negative for IgG, IgM, IgA, and C3, configuring an unspecific pattern of vascular reaction.

Please refer to the PDF to view the figures

The patient was diagnosed with eosinophilic fasciitis (Shulman syndrome), prescribed a therapeutic regimen of prednisone 20 mg/d (0.3 mg/kg) and diclofenac potassium 100 mg/d, and advised to avoid exercise and to rest. The patient's condition progressively improved, as did the cutaneous sclerosis, which improved faster in the upper limbs. After 6 months of prednisone with gradual withdrawal, examination results showed only a discrete sclerosis of the arms, forearms, thighs, and legs. 

Comment

Shulman syndrome, first described in 1974 by Shulman,¹ is characterized by a sudden onset of a symmetrical edema with induration at the extremities. In 1975, Rodnan et al² proposed the name eosinophilic fasciitis after evaluating a laboratorial aspect of the disease. At that time, more than 200 cases were reported, some in nonhuman primates such as the rhesus monkey.³

Eosinophilic fasciitis is an inflammatory disease of unknown etiology that affects the muscular fascia and is characterized by a considerable increase of serous and tissue eosinophils, with hypergammaglobulinemia.^4-6 This sclerodermiform syndrome presents clinical and histopathologic characteristics that allow a clinical distinction from scleroderma, despite that in some cases such differentiation may be difficult. Eosinophilic fasciitis mostly affects white men aged 30 to 70 years, frequently after the performance of vigorous and unusual physical effort. Patients complain about pain and edema with sudden onset and centripetal evolution starting at the extremities, evolving to induration that leads to limitation of hand and feet mobility.^7,8 Occasionally, the face and abdomen also may be involved.⁹ An important dermatologic sign for the diagnosis is called the valley signal, which can be observed during extension and abduction of the arms, and corresponds to the linear depression following the vascular path of the area involved. The description of 6 cases in the presence of hematologic neoplasia has led some authors to believe that eosinophilic fasciitis is a manifestation of a paraneoplastic syndrome.¹⁰

Since the first description of Shulman syndrome in the literature, the condition has appeared in more than 100 articles, mostly of Anglo-Saxon origin. These articles have generated much debate regarding the condition's relation to scleroderma or its existence as an autonomous entity.¹¹ The condition should be set apart from all other sclerodermiform states. Scleredema adultorum (Buschke disease) is related to respiratory infection or to diabetes mellitus of long evolution. Scleredema adultorum presents a centrifugal evolution, beginning at the cervical region and root of the upper limbs, with half of the cases occurring during childhood or adolescence, and is twice as frequent in women.⁸ Mucin is generally evident at the beginning of the disease.¹² Myalgia-eosinophilia syndrome presents respiratory and neurologic symptoms associated with myalgia of sudden onset and is accompanied by a temporary cutaneous eruption that varies from maculopapular to urticarial. Myalgia-eosinophilia syndrome may present intense itching, and is related to the ingestion of the amino acid L-tryptophan.^13-16 Systemic scleroderma presents a universal induration of the skin accompanied by vasospastic phenomena in several organs with a variety of symptoms. Patients with acroesclerosis, a form of systemic scleroderma, present with calcinosis, Raynaud phenomenon, esophageal alterations, sclerodactyly, and telangiectasis (also known as CREST syndrome) on the face and upper trunk. The circumscribed forms are characterized by several types of cutaneous lesions, which are localized and seldom accompanied by other alterations.^17-20

Peripheral eosinophilia is a common finding in patients with eosinophilic fasciitis, presenting in more than 80% of cases; it also may occur in different forms in systemic sclerosis (7%) and in localized scleroderma (31%).^17,21 In nonmedicated patients with eosinophilic fasciitis, peripheral eosinophilia was a consistent finding, even in those who had the disease for more than 30 months. Most authors define eosinophilia as an eosinophil count of more than 600 cells/cm³; however, others have defined it as 400 or even 300 cells/cm³, with existence of a relationship between the peripheral and tissue count of eosinophils in most cases. In one study, eosinophilia above 1000 cells/mm³ was found in 61% of patients, but only 1% had systemic sclerosis and 8% had the localized form, indicating that peripheral eosinophilia is not only more frequent and intense but also guides the diagnosis.^17,21 Tissue eosinophilia is more variable than peripheral eosinophilia.

In some cases, the peripheral eosinophils are present in numbers within reference range in a certain blood sample, showing that the finding may be temporary. It is important to make the differential diagnosis between systemic sclerosis, morphea, and eosinophilic fasciitis because they not only have different prognoses but also have different treatments.^21,22 Eosinophilic fasciitis responds well to systemic corticoid therapy; in scleroderma, steroids are not always useful, and morphea can remit spontaneously. Absence of Raynaud phenomenon and induration of the limbs after intense and unusual exercise help to establish the diagnosis of eosinophilic fasciitis. Fascia damage can be found, though rarely, in the late phases of systemic sclerosis. Proliferative fasciitis represents a pseudosarcomatous reaction involving the muscular fascia and the subcutaneous fibrous septum; in addition, despite not presenting eosinophilia, proliferative fasciitis affects the extremities of adults and may have trauma as an etiological factor.¹⁹

The diagnosis of eosinophilic fasciitis may be confirmed by histopathologic examination, results of which show an inflammatory infiltrate with eosinophils extending to the muscular fascia.¹⁹ Tissue eosinophilia is defined as the presence of 3 or more cells in the microscopic field.¹⁶ The eosinophils are present in the entire damaged area from disease onset; however, this must not be confused with disseminated eosinophilic collagenosis, in which the cells infiltrate several organs, leading to focal necrosis and necrotizing endarteritis. When the biopsy result does not reach a diagnosis of hypodermis and fascia, the sclerotic aspect prevails, which is not characteristic of eosinophilic fasciitis. In the initial phases of eosinophilic fasciitis, there are no significant epidermal and dermal alterations; in scleroderma, there are variable degrees of edema and sclerosis, and the inflammatory process, when present, occurs in the dermis and in the upper portion of the subcutaneous cell tissue.^8,19,20 

Case Report

A 35-year-old white man visited our Sector of Dermatology complaining about a feeling of increased weight and volume in his arms and legs that had started 2 months previously. The symptoms had begun 48 hours after a vigorous and unusual physical effort—carrying 30- to 40-kg boxes during a more than 2.5-hour period. When the patient sought medical assistance, his problem was diagnosed as rheumatism. He was prescribed a nonsteroidal anti-inflammatory drug, with partial improvement. A few days later, his condition evolved to hand and wrist joint induration lasting more than 2 hours that was associated with a discrete disturbance to his normal way of walking.

The patient did not exercise regularly and denied the use of medication containing L-tryptophan. He did not report any systemic signs and symptoms such as fever, reduced weight, hyporexia, dyspnea, difficulty swallowing solids and liquids, previous upper respiratory tract infections, recent history of hepatitis, diabetes mellitus, or similar cases in the family.

Results of a physical examination showed loss of weight and skin blushing. The patient was hydrated, acyanotic, anicteric, feverless, and eupneic. His arterial pressure was 120x80 mm Hg, with ample peripheral pulses. The patient showed atypical facies without edema, with normal wrinkling for his gender and age and a mouth opening of 4.5 cm. His thorax and abdomen were without abnormalities. His upper and lower limbs had increased volume with infiltration varying from discrete to moderate, without sustained depressions at finger pressure except on the extremities. There was absence of Raynaud phenomenon. Results of an examination of articulations showed absence of edema or synovitis of the knees, ankles, wrists, and hands; mobility was free and painless.

Results of a dermatologic examination revealed visible sclerosis of limb skin, which was more evident at the extremities and diminished in intensity in the direction of the proximal region; in addition, the affected area had a discrete yellowish color, scarcity of hair, and telangiectasia (Figures 1 and 2).

Please refer to the PDF to view the figures

Results of laboratory tests showed intense eosinophilia (28%: a blood count of 2500 eosinophils in 8900 leukocytes); an increased erythrocyte sedimentation rate; and hypergammaglobulinemia (35.7%). His immunologic profile was evaluated for antinuclear factor, anti-DNA, antitopoisomerase, and anticentromere antibodies; all test results were negative. Antibodies for human immunodeficiency virus and indicators for hepatitis also were negative. Urine sediment and parasitologic stool examinations, as well as an x-ray of the thorax, did not reveal alterations. An incisional biopsy down to the muscular fascia was performed with a scalpel on the anterior surface of the right forearm.

Results of a histopathologic examination with hematoxylin-eosin stain revealed an inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils around dermal vessels, mostly at the muscular fascia and adjacent adipose tissue (Figures 3 and 4). Results of direct immunofluorescence showed immunoreactivity to fibrinogen in some vessels of the superficial dermis; however, the results were negative for IgG, IgM, IgA, and C3, configuring an unspecific pattern of vascular reaction.

Please refer to the PDF to view the figures

The patient was diagnosed with eosinophilic fasciitis (Shulman syndrome), prescribed a therapeutic regimen of prednisone 20 mg/d (0.3 mg/kg) and diclofenac potassium 100 mg/d, and advised to avoid exercise and to rest. The patient's condition progressively improved, as did the cutaneous sclerosis, which improved faster in the upper limbs. After 6 months of prednisone with gradual withdrawal, examination results showed only a discrete sclerosis of the arms, forearms, thighs, and legs. 

Comment

Shulman syndrome, first described in 1974 by Shulman,¹ is characterized by a sudden onset of a symmetrical edema with induration at the extremities. In 1975, Rodnan et al² proposed the name eosinophilic fasciitis after evaluating a laboratorial aspect of the disease. At that time, more than 200 cases were reported, some in nonhuman primates such as the rhesus monkey.³

Eosinophilic fasciitis is an inflammatory disease of unknown etiology that affects the muscular fascia and is characterized by a considerable increase of serous and tissue eosinophils, with hypergammaglobulinemia.^4-6 This sclerodermiform syndrome presents clinical and histopathologic characteristics that allow a clinical distinction from scleroderma, despite that in some cases such differentiation may be difficult. Eosinophilic fasciitis mostly affects white men aged 30 to 70 years, frequently after the performance of vigorous and unusual physical effort. Patients complain about pain and edema with sudden onset and centripetal evolution starting at the extremities, evolving to induration that leads to limitation of hand and feet mobility.^7,8 Occasionally, the face and abdomen also may be involved.⁹ An important dermatologic sign for the diagnosis is called the valley signal, which can be observed during extension and abduction of the arms, and corresponds to the linear depression following the vascular path of the area involved. The description of 6 cases in the presence of hematologic neoplasia has led some authors to believe that eosinophilic fasciitis is a manifestation of a paraneoplastic syndrome.¹⁰

Since the first description of Shulman syndrome in the literature, the condition has appeared in more than 100 articles, mostly of Anglo-Saxon origin. These articles have generated much debate regarding the condition's relation to scleroderma or its existence as an autonomous entity.¹¹ The condition should be set apart from all other sclerodermiform states. Scleredema adultorum (Buschke disease) is related to respiratory infection or to diabetes mellitus of long evolution. Scleredema adultorum presents a centrifugal evolution, beginning at the cervical region and root of the upper limbs, with half of the cases occurring during childhood or adolescence, and is twice as frequent in women.⁸ Mucin is generally evident at the beginning of the disease.¹² Myalgia-eosinophilia syndrome presents respiratory and neurologic symptoms associated with myalgia of sudden onset and is accompanied by a temporary cutaneous eruption that varies from maculopapular to urticarial. Myalgia-eosinophilia syndrome may present intense itching, and is related to the ingestion of the amino acid L-tryptophan.^13-16 Systemic scleroderma presents a universal induration of the skin accompanied by vasospastic phenomena in several organs with a variety of symptoms. Patients with acroesclerosis, a form of systemic scleroderma, present with calcinosis, Raynaud phenomenon, esophageal alterations, sclerodactyly, and telangiectasis (also known as CREST syndrome) on the face and upper trunk. The circumscribed forms are characterized by several types of cutaneous lesions, which are localized and seldom accompanied by other alterations.^17-20

Peripheral eosinophilia is a common finding in patients with eosinophilic fasciitis, presenting in more than 80% of cases; it also may occur in different forms in systemic sclerosis (7%) and in localized scleroderma (31%).^17,21 In nonmedicated patients with eosinophilic fasciitis, peripheral eosinophilia was a consistent finding, even in those who had the disease for more than 30 months. Most authors define eosinophilia as an eosinophil count of more than 600 cells/cm³; however, others have defined it as 400 or even 300 cells/cm³, with existence of a relationship between the peripheral and tissue count of eosinophils in most cases. In one study, eosinophilia above 1000 cells/mm³ was found in 61% of patients, but only 1% had systemic sclerosis and 8% had the localized form, indicating that peripheral eosinophilia is not only more frequent and intense but also guides the diagnosis.^17,21 Tissue eosinophilia is more variable than peripheral eosinophilia.

In some cases, the peripheral eosinophils are present in numbers within reference range in a certain blood sample, showing that the finding may be temporary. It is important to make the differential diagnosis between systemic sclerosis, morphea, and eosinophilic fasciitis because they not only have different prognoses but also have different treatments.^21,22 Eosinophilic fasciitis responds well to systemic corticoid therapy; in scleroderma, steroids are not always useful, and morphea can remit spontaneously. Absence of Raynaud phenomenon and induration of the limbs after intense and unusual exercise help to establish the diagnosis of eosinophilic fasciitis. Fascia damage can be found, though rarely, in the late phases of systemic sclerosis. Proliferative fasciitis represents a pseudosarcomatous reaction involving the muscular fascia and the subcutaneous fibrous septum; in addition, despite not presenting eosinophilia, proliferative fasciitis affects the extremities of adults and may have trauma as an etiological factor.¹⁹

The diagnosis of eosinophilic fasciitis may be confirmed by histopathologic examination, results of which show an inflammatory infiltrate with eosinophils extending to the muscular fascia.¹⁹ Tissue eosinophilia is defined as the presence of 3 or more cells in the microscopic field.¹⁶ The eosinophils are present in the entire damaged area from disease onset; however, this must not be confused with disseminated eosinophilic collagenosis, in which the cells infiltrate several organs, leading to focal necrosis and necrotizing endarteritis. When the biopsy result does not reach a diagnosis of hypodermis and fascia, the sclerotic aspect prevails, which is not characteristic of eosinophilic fasciitis. In the initial phases of eosinophilic fasciitis, there are no significant epidermal and dermal alterations; in scleroderma, there are variable degrees of edema and sclerosis, and the inflammatory process, when present, occurs in the dermis and in the upper portion of the subcutaneous cell tissue.^8,19,20 

Case Report

A 35-year-old white man visited our Sector of Dermatology complaining about a feeling of increased weight and volume in his arms and legs that had started 2 months previously. The symptoms had begun 48 hours after a vigorous and unusual physical effort—carrying 30- to 40-kg boxes during a more than 2.5-hour period. When the patient sought medical assistance, his problem was diagnosed as rheumatism. He was prescribed a nonsteroidal anti-inflammatory drug, with partial improvement. A few days later, his condition evolved to hand and wrist joint induration lasting more than 2 hours that was associated with a discrete disturbance to his normal way of walking.

The patient did not exercise regularly and denied the use of medication containing L-tryptophan. He did not report any systemic signs and symptoms such as fever, reduced weight, hyporexia, dyspnea, difficulty swallowing solids and liquids, previous upper respiratory tract infections, recent history of hepatitis, diabetes mellitus, or similar cases in the family.

Results of a physical examination showed loss of weight and skin blushing. The patient was hydrated, acyanotic, anicteric, feverless, and eupneic. His arterial pressure was 120x80 mm Hg, with ample peripheral pulses. The patient showed atypical facies without edema, with normal wrinkling for his gender and age and a mouth opening of 4.5 cm. His thorax and abdomen were without abnormalities. His upper and lower limbs had increased volume with infiltration varying from discrete to moderate, without sustained depressions at finger pressure except on the extremities. There was absence of Raynaud phenomenon. Results of an examination of articulations showed absence of edema or synovitis of the knees, ankles, wrists, and hands; mobility was free and painless.

Results of a dermatologic examination revealed visible sclerosis of limb skin, which was more evident at the extremities and diminished in intensity in the direction of the proximal region; in addition, the affected area had a discrete yellowish color, scarcity of hair, and telangiectasia (Figures 1 and 2).

Please refer to the PDF to view the figures

Results of laboratory tests showed intense eosinophilia (28%: a blood count of 2500 eosinophils in 8900 leukocytes); an increased erythrocyte sedimentation rate; and hypergammaglobulinemia (35.7%). His immunologic profile was evaluated for antinuclear factor, anti-DNA, antitopoisomerase, and anticentromere antibodies; all test results were negative. Antibodies for human immunodeficiency virus and indicators for hepatitis also were negative. Urine sediment and parasitologic stool examinations, as well as an x-ray of the thorax, did not reveal alterations. An incisional biopsy down to the muscular fascia was performed with a scalpel on the anterior surface of the right forearm.

Results of a histopathologic examination with hematoxylin-eosin stain revealed an inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils around dermal vessels, mostly at the muscular fascia and adjacent adipose tissue (Figures 3 and 4). Results of direct immunofluorescence showed immunoreactivity to fibrinogen in some vessels of the superficial dermis; however, the results were negative for IgG, IgM, IgA, and C3, configuring an unspecific pattern of vascular reaction.

Please refer to the PDF to view the figures

The patient was diagnosed with eosinophilic fasciitis (Shulman syndrome), prescribed a therapeutic regimen of prednisone 20 mg/d (0.3 mg/kg) and diclofenac potassium 100 mg/d, and advised to avoid exercise and to rest. The patient's condition progressively improved, as did the cutaneous sclerosis, which improved faster in the upper limbs. After 6 months of prednisone with gradual withdrawal, examination results showed only a discrete sclerosis of the arms, forearms, thighs, and legs. 

Comment

Shulman syndrome, first described in 1974 by Shulman,¹ is characterized by a sudden onset of a symmetrical edema with induration at the extremities. In 1975, Rodnan et al² proposed the name eosinophilic fasciitis after evaluating a laboratorial aspect of the disease. At that time, more than 200 cases were reported, some in nonhuman primates such as the rhesus monkey.³

Eosinophilic fasciitis is an inflammatory disease of unknown etiology that affects the muscular fascia and is characterized by a considerable increase of serous and tissue eosinophils, with hypergammaglobulinemia.^4-6 This sclerodermiform syndrome presents clinical and histopathologic characteristics that allow a clinical distinction from scleroderma, despite that in some cases such differentiation may be difficult. Eosinophilic fasciitis mostly affects white men aged 30 to 70 years, frequently after the performance of vigorous and unusual physical effort. Patients complain about pain and edema with sudden onset and centripetal evolution starting at the extremities, evolving to induration that leads to limitation of hand and feet mobility.^7,8 Occasionally, the face and abdomen also may be involved.⁹ An important dermatologic sign for the diagnosis is called the valley signal, which can be observed during extension and abduction of the arms, and corresponds to the linear depression following the vascular path of the area involved. The description of 6 cases in the presence of hematologic neoplasia has led some authors to believe that eosinophilic fasciitis is a manifestation of a paraneoplastic syndrome.¹⁰

Since the first description of Shulman syndrome in the literature, the condition has appeared in more than 100 articles, mostly of Anglo-Saxon origin. These articles have generated much debate regarding the condition's relation to scleroderma or its existence as an autonomous entity.¹¹ The condition should be set apart from all other sclerodermiform states. Scleredema adultorum (Buschke disease) is related to respiratory infection or to diabetes mellitus of long evolution. Scleredema adultorum presents a centrifugal evolution, beginning at the cervical region and root of the upper limbs, with half of the cases occurring during childhood or adolescence, and is twice as frequent in women.⁸ Mucin is generally evident at the beginning of the disease.¹² Myalgia-eosinophilia syndrome presents respiratory and neurologic symptoms associated with myalgia of sudden onset and is accompanied by a temporary cutaneous eruption that varies from maculopapular to urticarial. Myalgia-eosinophilia syndrome may present intense itching, and is related to the ingestion of the amino acid L-tryptophan.^13-16 Systemic scleroderma presents a universal induration of the skin accompanied by vasospastic phenomena in several organs with a variety of symptoms. Patients with acroesclerosis, a form of systemic scleroderma, present with calcinosis, Raynaud phenomenon, esophageal alterations, sclerodactyly, and telangiectasis (also known as CREST syndrome) on the face and upper trunk. The circumscribed forms are characterized by several types of cutaneous lesions, which are localized and seldom accompanied by other alterations.^17-20

Peripheral eosinophilia is a common finding in patients with eosinophilic fasciitis, presenting in more than 80% of cases; it also may occur in different forms in systemic sclerosis (7%) and in localized scleroderma (31%).^17,21 In nonmedicated patients with eosinophilic fasciitis, peripheral eosinophilia was a consistent finding, even in those who had the disease for more than 30 months. Most authors define eosinophilia as an eosinophil count of more than 600 cells/cm³; however, others have defined it as 400 or even 300 cells/cm³, with existence of a relationship between the peripheral and tissue count of eosinophils in most cases. In one study, eosinophilia above 1000 cells/mm³ was found in 61% of patients, but only 1% had systemic sclerosis and 8% had the localized form, indicating that peripheral eosinophilia is not only more frequent and intense but also guides the diagnosis.^17,21 Tissue eosinophilia is more variable than peripheral eosinophilia.

In some cases, the peripheral eosinophils are present in numbers within reference range in a certain blood sample, showing that the finding may be temporary. It is important to make the differential diagnosis between systemic sclerosis, morphea, and eosinophilic fasciitis because they not only have different prognoses but also have different treatments.^21,22 Eosinophilic fasciitis responds well to systemic corticoid therapy; in scleroderma, steroids are not always useful, and morphea can remit spontaneously. Absence of Raynaud phenomenon and induration of the limbs after intense and unusual exercise help to establish the diagnosis of eosinophilic fasciitis. Fascia damage can be found, though rarely, in the late phases of systemic sclerosis. Proliferative fasciitis represents a pseudosarcomatous reaction involving the muscular fascia and the subcutaneous fibrous septum; in addition, despite not presenting eosinophilia, proliferative fasciitis affects the extremities of adults and may have trauma as an etiological factor.¹⁹

The diagnosis of eosinophilic fasciitis may be confirmed by histopathologic examination, results of which show an inflammatory infiltrate with eosinophils extending to the muscular fascia.¹⁹ Tissue eosinophilia is defined as the presence of 3 or more cells in the microscopic field.¹⁶ The eosinophils are present in the entire damaged area from disease onset; however, this must not be confused with disseminated eosinophilic collagenosis, in which the cells infiltrate several organs, leading to focal necrosis and necrotizing endarteritis. When the biopsy result does not reach a diagnosis of hypodermis and fascia, the sclerotic aspect prevails, which is not characteristic of eosinophilic fasciitis. In the initial phases of eosinophilic fasciitis, there are no significant epidermal and dermal alterations; in scleroderma, there are variable degrees of edema and sclerosis, and the inflammatory process, when present, occurs in the dermis and in the upper portion of the subcutaneous cell tissue.^8,19,20