PEDIATRIC DERMATOLOGY PHOTOQUIZ Editor: Maureen Rogers, M.D., F.A.C.D.
PROGRESSIVE SCALP PLAQUE
IN A
GIRL
WITH
TUBEROUS SCLEROSIS
Megan M. Brown, B.S.,* Erica J. Walsh, M.D.,† Limin Yu, M.D., M.S.,‡ and Aimee C. Smidt, M.D.†,§ *School of Medicine, University of New Mexico, Albuquerque, New Mexico, Departments of †Dermatology, ‡Pathology, §Pediatrics, School of Medicine, University of New Mexico, Albuquerque, New Mexico
Case Presentation A 13-year-old girl with tuberous sclerosis presented with a 4.5-cm 9 6-cm painless, firm, exophytic, pink plaque studded with multiple comedo-like openings on the occipital scalp (Fig. 1). The lesion had been present since birth, but several months before dermatologic evaluation it started increasing in size and interfering with hair brushing and styling. Manipulation of the lesion intermittently caused the expression of blood and pus. A punch biopsy was performed, with expectation of surgical excision to follow, depending on pathology results.
What is the diagnosis?
Figure 1.
ERYTHEMATOUS PURPURIC INDURATED PLAQUE OVER RIGHT FOREARM Rim S. Ishak, M.D., Mazen Kurban, M.D., and Ossama Abbas, M.D. Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
A 15-year-old boy known to have T-cell acute lymphoblastic leukemia (ALL) and undergoing induction chemotherapy (vincristine, daunorubicin, L-asparaginase, cytarabine, mercaptopurine) presented with a 2-week history of painful lesions on the right forearm (Fig. 1). The lesions appeared at the intravenous (IV) site and were initially thought to be thrombophlebitis, but they persisted despite removal of the IV needle. The patient was then treated with vancomycin and cefepime for 6 days for suspected cellulitis with no improvement, and finally acyclovir was added when herpes simplex was suspected as the cause of these lesions. Finally, we were consulted in view of the lack of response to the aforementioned treatments. Physical examination revealed a tender, erythematous, indurated, warm plaque over the right forearm, with several hemorrhagic flaccid small blisters on its surface (Fig. 1). There was a surrounding area of erythema, edema, and warmth. A swab was taken for bacterial and fungal culture and a punch biopsy for histopathology (Figs. 2 and 3), and tissue culture was performed.
Figure 3.
Figure 1.
What is the diagnosis?
Figure 2.
ASYMPTOMATIC SKIN-COLORED PLAQUE
IN AN
8-YEAR-OLD GIRL
Magdalena Herna´ndez, M.D.,*† Antonio Torrelo, M.D.,* Angela Herna´ndez-Martı´n, M.D.,* Isabel Colmenero, M.D.,‡ Fernando Casco, M.D.,‡ and Mercedes Alvarez, M.D.§ *Department of Dermatology, Hospital Infantil Universitario Nin˜o Jesu´s, Madrid, Spain, †Department of Dermatology, Hospital Privado de Co´rdoba, Co´rdoba, Argentina, ‡Department of Pathology, Hospital Infantil Universitario Nin˜o Jesu´s, Madrid, Spain, §Servicio De Cirugia, Hospital Pediatrico Nin˜o Jesus, Madrid, Spain
Case Presentation An 8-year-old girl presented with an asymptomatic lesion on the right side of her neck. According to her mother, the lesion had been present since she was 6 years old and had not changed in appearance over the previous 2 years. There was no history of trauma at the site of involvement. The girl was otherwise healthy and her family history was unremarkable. The lesion consisted of an ill-defined, skin-colored, noninflammatory plaque. It measured 1.2 cm 9 1.5 cm and was fixed to the overlying skin but was movable over the deeper tissue (Fig. 1). An excisional biopsy was performed and the histology is shown in Figs. 2 and 3.
Figure 1.
Figure 3.
What is the diagnosis?
Figure 2.
249
PROGRESSIVE SCALP PLAQUE Diagnosis: Folliculocystic and collagen hamartoma of tuberous sclerosis complex
Microscopic Findings Histopathology showed keratin-containing comedo cysts with perifollicular acute and granulomatous infiltrates (Fig. 2). Thickened collagen bundles (Fig. 3) and increased numbers of interstitial cells were also present in the dermis and extend into the underlying adipose tissue. These findings are compatible with a folliculocystic and collagen hamartoma of tuberous sclerosis complex.
Discussion The recent publication by Torrelo et al (1) on “Folliculocystic and collagen hamartoma of tuberous sclerosis complex” provided an excellent description of a newly discovered hamartoma in patients with tuberous sclerosis complex (TSC). It is a rare entity, described in a small cohort of six male patients, five of whom had a clinical diagnosis of TSC.
IN A
GIRL
WITH
TUBEROUS SCLEROSIS
Folliculocystic and collagen hamartomas (FCH) present as painless papules or plaques with elastic consistency and many comedo-like openings (1). They have been observed on the occipital scalp, abdomen, lumbar region, and thigh. Histologically they show abundant collagen deposition, keratincontaining comedo cysts, and concentric perifollicular fibrosis (1). Our patient’s biopsy exhibited these typical findings of FCH. Molecular testing may be used in some patients to make the initial diagnosis of TSC. The pathogenesis of hamartomatous lesions in TSC is generally linked to mutations in the genes TSC1 (hamartin protein) and TSC2 (tuberin protein) (2,3). Hamartin and tuberin bind together as a heterodimer that functions as a tumor suppressor. Hamartomas have high mTORC1 activity secondary to lack of inhibition by this TSC tumor suppressor complex. The high mTORC1 activity stimulates cell overproliferation with proliferation of fibroblasts and normal keratinocytes to form normal hair follicles with sebaceous glands (3,4).
The exact mechanism of the formation of FCH is not fully elucidated, although it may be similar. Fibrous hamartoma of infancy (a similar lesion to FHC that also occurs in TSC) may be treated successfully with surgical excision (5). Pharmacologic therapy for tumors in TSC is focused on rapamycin inhibitors. One of the properties of rapamycin inhibitors is direct binding and inhibition of mTORC1. Rapamycin inhibitors have proved effective in decreasing the size and slowing the growth of multiple TSC-related tumors, including angiofibromas, angiomyolipomas, and subependymal giant cell astrocytomas (4). Further research is needed on surgical and medical therapy for FCHs. To our knowledge, this represents the first reported case of an FCH in a female patient with TSC. At the 6-month follow-up, the lesion had continued to increase in size and was uncomfortable for the patient. She was referred to plastic surgery for full surgical excision.
References 1. Torrelo A, Hadj-Rabia S, Colmenero I et al. Folliculocystic and collagen hamartoma of tuberous sclerosis complex. J Am Acad Dermatol 2012;66:617–621. 2. Misago N, Kimura T, Toda S et al. A revaluation of folliculosebaceous cystic hamartoma: the histopathological and immunohistochemical features. Am J Dermatopathol 2010;32:154–161. 3. Jozwiak J, Galus R. Molecular implications of skin lesions in tuberous sclerosis. Am J Dermatopathol 2008;30:256–261. 4. Kohrman MH. Emerging treatments in the management of tuberous sclerosis complex. Pediatr Neurol 2012;46:267– 275. 5. Kang G, Suh YL, Han J et al. Fibrous hamartoma of infancy: an experience of a single institute. J Korean Surg Soc 2011;81:61–65. Address correspondence to Aimee C. Smidt, M.D., 1021 Medical Arts Ave., Albuquerque, NM 87131, or e-mail: [email protected].
Figure 2.
Figure 3.
ERYTHEMATOUS PURPURIC INDURATED PLAQUE OVER RIGHT FOREARM Diagnosis: Cutaneous mucormycosis
Microscopic and Laboratory Findings Histopathology revealed numerous broad-based, nonseptated large hyphae with right-angled branching suggestive of Zygomycetes (Figs. 2 and 3). These hyphae were highlighted on periodic acid-Schiff (PAS) stains. Tissue cultures grew Zygomycetes species. Examination for systemic Rhizopus infection, including computed tomography of the sinuses, chest, and abdomen, demonstrated no evidence of infection elsewhere. The patient was given liposomal amphotericin B intravenously (5 mg/kg/day) for 34 days and he underwent surgical debridement with grafting from skin over the right thigh. The lesions disappeared and the graft completely healed with no recurrence of the lesions.
Discussion Rhizopus, which belongs to the class Zygomycetes and the order Mucorales (mucormycosis), is a ubiquitous organism found in soil and decaying organic matter. It is a rapid grower and can tolerate temperatures greater than 37°C, accounting for its virulence (1). This fungus usually causes opportunistic infections, mainly occurring in immunocompromised patients, particularly those with neutropenia, because normal-functioning neutrophils are the major host defense against Zygomycetes (2). Individuals with uncontrolled diabetes, organ transplantation, and hematologic malignancy are particularly susceptible (3). Rhizopus is characteristically angioinvasive, causing quick soft tissue destruction, and may be rapidly progressive and fatal, with overall mortality exceeding 65% (3).
Mucormycosis manifests in one of five clinical forms: rhino-orbitocerebral, pulmonary, gastrointestinal, cutaneous, and disseminated disease (3). Rhinocerebral infections and orbital cellulitis are most commonly seen in patients with diabetes mellitus, particularly those with diabetic ketoacidosis. The primary cutaneous variant typically presents as a single necrotic hemorrhagic ulcer after percutaneous inoculation of the fungal spores (4). Even minor trauma, such as that from mosquito bites, intravenous catheters, wooden tongue depressors, and adhesive elastic bandages, may be accountable (5). Cutaneous infections are classified as superficial or gangrenous. Superficial infections have a gradual onset, with slow progression, and are without systemic symptoms, whereas gangrenous infections present as progressive painful ulcers and eschars that invade the underlying tissues, resulting in a fulminant course (2). Diagnosis is accomplished by histopathologic examination and fungal tissue culture. Rhizopus has broad (10–20 lm in diameter) nonseptate hyphae with irregular branching at 90°, best seen using Grocott’s methenamine silver stain. Accurate species identification can be achieved using fungal tissue culture and lactophenol cotton blue staining (2). Treatment entails a combination of surgical debridement and prompt medical therapy with amphotericin B (5). Other antifungal agents, such as the azoles, are generally ineffective in treating mucormycosis (6). Some authors suggest that liposomal amphotericin B is the drug of choice and that posaconazole is the alternative agent of choice (5). Mortality depends on the extent and the location of the disease, in addition to the immune status of the patient. Cutaneous mucormycosis has the best outcome, with 15% associated mortality (3).
ASYMPTOMATIC SKIN-COLORED PLAQUE Diagnosis: Dermatomyofibroma
Histopathology Histologic examination showed an epidermis with no significant changes and a uniform, spindleshaped cell proliferation in the mid and deeper dermis arranged predominantly parallel to the skin surface (Fig. 2). These cells had a weakly eosinophilic cytoplasm with poorly demarcated margins and elongated nuclei and were gathered together in a fascicular pattern. Neither atypia nor mitoses were observed. The adnexal structures were spared, and there was no inflammatory infiltrate (Fig. 3). The cells did not stain for smooth muscle actin or S-100 on immunohistochemistry.
Discussion Dermatomyofibroma is an uncommon benign cutaneous tumor with fibroblastic and myofibroblastic differentiation (1,2). It is mainly found in young women and is usually located on the shoulder and adjacent regions, with only a few cases reported in males (3,4). Whereas the morphologic and immunophenotypical features of the lesions are homogeneous in all age groups, other characteristics of pediatric patients, such as sex distribution and preferential locations, differ from those in adults. Dermatomyofibromas in children have been rarely reported; they occur more commonly in boys and their most frequent location is the neck (1). Almost all cases appear as solitary, small, asymptomatic, plaque-like lesions with an average diameter of 1 to 2 cm (5), but they may occasionally reach a considerable size (3). They are skin colored or may have a
IN AN
tan to red surface discoloration (5). It has been speculated that dermatomyofibromas regress spontaneously after childhood in males, whereas in females they continue to grow slowly or become stabilized after puberty, possibly under hormonal influence (4). The clinical differential diagnoses of dermatomyofibroma include dermatofibroma, granuloma annulare, benign cyst, lipoma, hypertrophic scar, keloid, neural tumor, pilomatricoma, dermatofibrosarcoma protuberans, and pseudolymphoma (5). Histologically, dermatomyofibroma shows a plaque-like proliferation of uniform, spindleshaped, myofibroblastic cells arranged in elongated intersecting fascicles predominantly parallel to the epidermis and in ill-defined nodules in the mid and deeper dermis. These cells have a bland fusiform nucleus and a weakly eosinophilic cytoplasm with poorly demarcated margins. Mitoses and cytologic atypia are not observed. Numerous elastic fibers, sometimes enlarged and fragmented, can be found intermingled with the fascicles. Adnexal structures are usually spared, and there is no inflammatory infiltrate (1,6). Tumor cells all stain positively for vimentin on immunohistochemistry, and most stain for calponin. Variable coexpression of smooth muscle actin and muscle-specific actin has been observed, and focal positivity for CD34 has been reported in some cases. They are generally negative for b catenin (1). Ultrastructural study confirms that it is a proliferation of fibroblasts and myofibroblasts (7). The histologic differential diagnosis includes other spindle cell lesions, particularly infantile myofibromatosis and diffuse neurofibroma. Myofibromas demonstrate hemangiopericytoma-like
250
This is the second report of cutaneous mucormycosis developing during induction chemotherapy for T-cell ALL in a child (7). A high index of suspicion is necessary for the diagnosis of mucormycosis in these children, and a punch biopsy should be performed immediately to identify the organism, followed promptly by commencement of antifungal therapy and surgical debridement to reduce the high rate of fatality seen with this fungus.
References 1. Gonzalez CE, Rinaldi MG, Sugar AM. Zygomycosis. Infect Dis Clin North Am 2002;16:895–914. 2. Xu LY, Bandow GD, Heffernan MP. Crusted violaceous plaques on an immunocompromised host. Arch Dermatol 2007;143:417–422. 3. Adam RD, Hunter G, DiTomasso J et al. Mucormycosis: emerging prominence of cutaneous infections. Clin Infect Dis 1994;19:67–76. 4. Losee JE, Selber J, Vega S et al. Primary cutaneous mucormycosis: guide to surgical management. Ann Plast Surg 2002;49:385–390. 5. Burdick LM, Hamrock D, Mawhorter S et al. JAAD Grand Rounds quiz. Asymptomatic necrotic ulcer on leg. J Am Acad Dermatol 2009;61:172–174. 6. Rubin AI, Grossman ME. Bull’s-eye cutaneous infarct of zygomycosis: a bedside diagnosis confirmed by touch preparation. J Am Acad Dermatol 2004;51:996–1001. 7. Sankar J, Arun S, Sankar MJ et al. Primary cutaneous mucormycosis during induction chemotherapy in a child with acute lymphoblastic leukemia. Indian J Pediatr 2009;76: 1161–1163. Address correspondence to Ossama Abbas, M.D., Department of Dermatology, American University of Beirut Medical Center, P.O. Box-11-0236, Riad El Solh/Beirut 1107 2020, Beirut, Lebanon, or e-mail: [email protected].
8-YEAR-OLD GIRL areas and spindle cell fascicles, and the latter are not arranged parallel to the epidermis. Diffuse neurofibroma can be differentiated from dermatomyofibroma according to its S-100 positivity (1). Dermatomyofibroma is a benign tumor and does not tend to recur (3), so it is proposed that clinical follow-up without surgical excision is appropriate in some cases and may be considered in locations in which surgery could produce significant cosmetic defects (1).
References 1. Tardı´o JC, Herna´ndez-Nu´n˜ez A, Guzma´n A et al. Dermatomyofibromas presenting in pediatric patients: clinicopathologic characteristics and differential diagnosis. J Cutan Pathol 2011;38:967–972. 2. Go´mez-Moyano E, Vera-Casan˜o A, Martı´nez-Garcı´a S et al. Two cases of dermatomyofibroma (plaque-like dermal fibromatosis). Int J Dermatol 2010;49:914–917. 3. Gilaberte Y, Coscojuela C, Doste D et al. Dermatomyofibroma in a male child. J Eur Acad Dermatol Venereol 2005;19:257–259. 4. Rose C, Bro¨cker E-B. Dermatomyofibroma: case report and review. Pediatr Dermatol 1999;16:456–459. 5. Holst V, Junkins Hopkins J, Elenitsas K. Cutaneous smooth muscle neoplasms: clinical features, histologic findings, and treatment options. J Am Acad Dermatol 2002;46:477–490. 6. Viglizzo G, Occella C, Calonje E et al. A unique case of multiple dermatomyofibromas. Clin Dermatol 2008;33:622– 624. 7. Patrizi A, Vespignani MF, Rizzoli L et al. An asymptomatic abdominal nodule in a 5-year-old boy. Pediatr Dermatol 1999;16:154–156. Address correspondence to Magdalena Herna´ndez, M.D., Hospital Privado de Co´rdoba, Department of Dermatology, Naciones Unidas 364, Co´rdoba, Argentina, or e-mail: [email protected].
PROGRESSIVE SCALP PLAQUE
IN A
GIRL
WITH
TUBEROUS SCLEROSIS
Megan M. Brown, B.S.,* Erica J. Walsh, M.D.,† Limin Yu, M.D., M.S.,‡ and Aimee C. Smidt, M.D.†,§ *School of Medicine, University of New Mexico, Albuquerque, New Mexico, Departments of †Dermatology, ‡Pathology, §Pediatrics, School of Medicine, University of New Mexico, Albuquerque, New Mexico
Case Presentation A 13-year-old girl with tuberous sclerosis presented with a 4.5-cm 9 6-cm painless, firm, exophytic, pink plaque studded with multiple comedo-like openings on the occipital scalp (Fig. 1). The lesion had been present since birth, but several months before dermatologic evaluation it started increasing in size and interfering with hair brushing and styling. Manipulation of the lesion intermittently caused the expression of blood and pus. A punch biopsy was performed, with expectation of surgical excision to follow, depending on pathology results.
What is the diagnosis?
Figure 1.
ERYTHEMATOUS PURPURIC INDURATED PLAQUE OVER RIGHT FOREARM Rim S. Ishak, M.D., Mazen Kurban, M.D., and Ossama Abbas, M.D. Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
A 15-year-old boy known to have T-cell acute lymphoblastic leukemia (ALL) and undergoing induction chemotherapy (vincristine, daunorubicin, L-asparaginase, cytarabine, mercaptopurine) presented with a 2-week history of painful lesions on the right forearm (Fig. 1). The lesions appeared at the intravenous (IV) site and were initially thought to be thrombophlebitis, but they persisted despite removal of the IV needle. The patient was then treated with vancomycin and cefepime for 6 days for suspected cellulitis with no improvement, and finally acyclovir was added when herpes simplex was suspected as the cause of these lesions. Finally, we were consulted in view of the lack of response to the aforementioned treatments. Physical examination revealed a tender, erythematous, indurated, warm plaque over the right forearm, with several hemorrhagic flaccid small blisters on its surface (Fig. 1). There was a surrounding area of erythema, edema, and warmth. A swab was taken for bacterial and fungal culture and a punch biopsy for histopathology (Figs. 2 and 3), and tissue culture was performed.
Figure 3.
Figure 1.
What is the diagnosis?
Figure 2.
ASYMPTOMATIC SKIN-COLORED PLAQUE
IN AN
8-YEAR-OLD GIRL
Magdalena Herna´ndez, M.D.,*† Antonio Torrelo, M.D.,* Angela Herna´ndez-Martı´n, M.D.,* Isabel Colmenero, M.D.,‡ Fernando Casco, M.D.,‡ and Mercedes Alvarez, M.D.§ *Department of Dermatology, Hospital Infantil Universitario Nin˜o Jesu´s, Madrid, Spain, †Department of Dermatology, Hospital Privado de Co´rdoba, Co´rdoba, Argentina, ‡Department of Pathology, Hospital Infantil Universitario Nin˜o Jesu´s, Madrid, Spain, §Servicio De Cirugia, Hospital Pediatrico Nin˜o Jesus, Madrid, Spain
Case Presentation An 8-year-old girl presented with an asymptomatic lesion on the right side of her neck. According to her mother, the lesion had been present since she was 6 years old and had not changed in appearance over the previous 2 years. There was no history of trauma at the site of involvement. The girl was otherwise healthy and her family history was unremarkable. The lesion consisted of an ill-defined, skin-colored, noninflammatory plaque. It measured 1.2 cm 9 1.5 cm and was fixed to the overlying skin but was movable over the deeper tissue (Fig. 1). An excisional biopsy was performed and the histology is shown in Figs. 2 and 3.
Figure 1.
Figure 3.
What is the diagnosis?
Figure 2.
249
PROGRESSIVE SCALP PLAQUE Diagnosis: Folliculocystic and collagen hamartoma of tuberous sclerosis complex
Microscopic Findings Histopathology showed keratin-containing comedo cysts with perifollicular acute and granulomatous infiltrates (Fig. 2). Thickened collagen bundles (Fig. 3) and increased numbers of interstitial cells were also present in the dermis and extend into the underlying adipose tissue. These findings are compatible with a folliculocystic and collagen hamartoma of tuberous sclerosis complex.
Discussion The recent publication by Torrelo et al (1) on “Folliculocystic and collagen hamartoma of tuberous sclerosis complex” provided an excellent description of a newly discovered hamartoma in patients with tuberous sclerosis complex (TSC). It is a rare entity, described in a small cohort of six male patients, five of whom had a clinical diagnosis of TSC.
IN A
GIRL
WITH
TUBEROUS SCLEROSIS
Folliculocystic and collagen hamartomas (FCH) present as painless papules or plaques with elastic consistency and many comedo-like openings (1). They have been observed on the occipital scalp, abdomen, lumbar region, and thigh. Histologically they show abundant collagen deposition, keratincontaining comedo cysts, and concentric perifollicular fibrosis (1). Our patient’s biopsy exhibited these typical findings of FCH. Molecular testing may be used in some patients to make the initial diagnosis of TSC. The pathogenesis of hamartomatous lesions in TSC is generally linked to mutations in the genes TSC1 (hamartin protein) and TSC2 (tuberin protein) (2,3). Hamartin and tuberin bind together as a heterodimer that functions as a tumor suppressor. Hamartomas have high mTORC1 activity secondary to lack of inhibition by this TSC tumor suppressor complex. The high mTORC1 activity stimulates cell overproliferation with proliferation of fibroblasts and normal keratinocytes to form normal hair follicles with sebaceous glands (3,4).
The exact mechanism of the formation of FCH is not fully elucidated, although it may be similar. Fibrous hamartoma of infancy (a similar lesion to FHC that also occurs in TSC) may be treated successfully with surgical excision (5). Pharmacologic therapy for tumors in TSC is focused on rapamycin inhibitors. One of the properties of rapamycin inhibitors is direct binding and inhibition of mTORC1. Rapamycin inhibitors have proved effective in decreasing the size and slowing the growth of multiple TSC-related tumors, including angiofibromas, angiomyolipomas, and subependymal giant cell astrocytomas (4). Further research is needed on surgical and medical therapy for FCHs. To our knowledge, this represents the first reported case of an FCH in a female patient with TSC. At the 6-month follow-up, the lesion had continued to increase in size and was uncomfortable for the patient. She was referred to plastic surgery for full surgical excision.
References 1. Torrelo A, Hadj-Rabia S, Colmenero I et al. Folliculocystic and collagen hamartoma of tuberous sclerosis complex. J Am Acad Dermatol 2012;66:617–621. 2. Misago N, Kimura T, Toda S et al. A revaluation of folliculosebaceous cystic hamartoma: the histopathological and immunohistochemical features. Am J Dermatopathol 2010;32:154–161. 3. Jozwiak J, Galus R. Molecular implications of skin lesions in tuberous sclerosis. Am J Dermatopathol 2008;30:256–261. 4. Kohrman MH. Emerging treatments in the management of tuberous sclerosis complex. Pediatr Neurol 2012;46:267– 275. 5. Kang G, Suh YL, Han J et al. Fibrous hamartoma of infancy: an experience of a single institute. J Korean Surg Soc 2011;81:61–65. Address correspondence to Aimee C. Smidt, M.D., 1021 Medical Arts Ave., Albuquerque, NM 87131, or e-mail: [email protected].
Figure 2.
Figure 3.
ERYTHEMATOUS PURPURIC INDURATED PLAQUE OVER RIGHT FOREARM Diagnosis: Cutaneous mucormycosis
Microscopic and Laboratory Findings Histopathology revealed numerous broad-based, nonseptated large hyphae with right-angled branching suggestive of Zygomycetes (Figs. 2 and 3). These hyphae were highlighted on periodic acid-Schiff (PAS) stains. Tissue cultures grew Zygomycetes species. Examination for systemic Rhizopus infection, including computed tomography of the sinuses, chest, and abdomen, demonstrated no evidence of infection elsewhere. The patient was given liposomal amphotericin B intravenously (5 mg/kg/day) for 34 days and he underwent surgical debridement with grafting from skin over the right thigh. The lesions disappeared and the graft completely healed with no recurrence of the lesions.
Discussion Rhizopus, which belongs to the class Zygomycetes and the order Mucorales (mucormycosis), is a ubiquitous organism found in soil and decaying organic matter. It is a rapid grower and can tolerate temperatures greater than 37°C, accounting for its virulence (1). This fungus usually causes opportunistic infections, mainly occurring in immunocompromised patients, particularly those with neutropenia, because normal-functioning neutrophils are the major host defense against Zygomycetes (2). Individuals with uncontrolled diabetes, organ transplantation, and hematologic malignancy are particularly susceptible (3). Rhizopus is characteristically angioinvasive, causing quick soft tissue destruction, and may be rapidly progressive and fatal, with overall mortality exceeding 65% (3).
Mucormycosis manifests in one of five clinical forms: rhino-orbitocerebral, pulmonary, gastrointestinal, cutaneous, and disseminated disease (3). Rhinocerebral infections and orbital cellulitis are most commonly seen in patients with diabetes mellitus, particularly those with diabetic ketoacidosis. The primary cutaneous variant typically presents as a single necrotic hemorrhagic ulcer after percutaneous inoculation of the fungal spores (4). Even minor trauma, such as that from mosquito bites, intravenous catheters, wooden tongue depressors, and adhesive elastic bandages, may be accountable (5). Cutaneous infections are classified as superficial or gangrenous. Superficial infections have a gradual onset, with slow progression, and are without systemic symptoms, whereas gangrenous infections present as progressive painful ulcers and eschars that invade the underlying tissues, resulting in a fulminant course (2). Diagnosis is accomplished by histopathologic examination and fungal tissue culture. Rhizopus has broad (10–20 lm in diameter) nonseptate hyphae with irregular branching at 90°, best seen using Grocott’s methenamine silver stain. Accurate species identification can be achieved using fungal tissue culture and lactophenol cotton blue staining (2). Treatment entails a combination of surgical debridement and prompt medical therapy with amphotericin B (5). Other antifungal agents, such as the azoles, are generally ineffective in treating mucormycosis (6). Some authors suggest that liposomal amphotericin B is the drug of choice and that posaconazole is the alternative agent of choice (5). Mortality depends on the extent and the location of the disease, in addition to the immune status of the patient. Cutaneous mucormycosis has the best outcome, with 15% associated mortality (3).
ASYMPTOMATIC SKIN-COLORED PLAQUE Diagnosis: Dermatomyofibroma
Histopathology Histologic examination showed an epidermis with no significant changes and a uniform, spindleshaped cell proliferation in the mid and deeper dermis arranged predominantly parallel to the skin surface (Fig. 2). These cells had a weakly eosinophilic cytoplasm with poorly demarcated margins and elongated nuclei and were gathered together in a fascicular pattern. Neither atypia nor mitoses were observed. The adnexal structures were spared, and there was no inflammatory infiltrate (Fig. 3). The cells did not stain for smooth muscle actin or S-100 on immunohistochemistry.
Discussion Dermatomyofibroma is an uncommon benign cutaneous tumor with fibroblastic and myofibroblastic differentiation (1,2). It is mainly found in young women and is usually located on the shoulder and adjacent regions, with only a few cases reported in males (3,4). Whereas the morphologic and immunophenotypical features of the lesions are homogeneous in all age groups, other characteristics of pediatric patients, such as sex distribution and preferential locations, differ from those in adults. Dermatomyofibromas in children have been rarely reported; they occur more commonly in boys and their most frequent location is the neck (1). Almost all cases appear as solitary, small, asymptomatic, plaque-like lesions with an average diameter of 1 to 2 cm (5), but they may occasionally reach a considerable size (3). They are skin colored or may have a
IN AN
tan to red surface discoloration (5). It has been speculated that dermatomyofibromas regress spontaneously after childhood in males, whereas in females they continue to grow slowly or become stabilized after puberty, possibly under hormonal influence (4). The clinical differential diagnoses of dermatomyofibroma include dermatofibroma, granuloma annulare, benign cyst, lipoma, hypertrophic scar, keloid, neural tumor, pilomatricoma, dermatofibrosarcoma protuberans, and pseudolymphoma (5). Histologically, dermatomyofibroma shows a plaque-like proliferation of uniform, spindleshaped, myofibroblastic cells arranged in elongated intersecting fascicles predominantly parallel to the epidermis and in ill-defined nodules in the mid and deeper dermis. These cells have a bland fusiform nucleus and a weakly eosinophilic cytoplasm with poorly demarcated margins. Mitoses and cytologic atypia are not observed. Numerous elastic fibers, sometimes enlarged and fragmented, can be found intermingled with the fascicles. Adnexal structures are usually spared, and there is no inflammatory infiltrate (1,6). Tumor cells all stain positively for vimentin on immunohistochemistry, and most stain for calponin. Variable coexpression of smooth muscle actin and muscle-specific actin has been observed, and focal positivity for CD34 has been reported in some cases. They are generally negative for b catenin (1). Ultrastructural study confirms that it is a proliferation of fibroblasts and myofibroblasts (7). The histologic differential diagnosis includes other spindle cell lesions, particularly infantile myofibromatosis and diffuse neurofibroma. Myofibromas demonstrate hemangiopericytoma-like
250
This is the second report of cutaneous mucormycosis developing during induction chemotherapy for T-cell ALL in a child (7). A high index of suspicion is necessary for the diagnosis of mucormycosis in these children, and a punch biopsy should be performed immediately to identify the organism, followed promptly by commencement of antifungal therapy and surgical debridement to reduce the high rate of fatality seen with this fungus.
References 1. Gonzalez CE, Rinaldi MG, Sugar AM. Zygomycosis. Infect Dis Clin North Am 2002;16:895–914. 2. Xu LY, Bandow GD, Heffernan MP. Crusted violaceous plaques on an immunocompromised host. Arch Dermatol 2007;143:417–422. 3. Adam RD, Hunter G, DiTomasso J et al. Mucormycosis: emerging prominence of cutaneous infections. Clin Infect Dis 1994;19:67–76. 4. Losee JE, Selber J, Vega S et al. Primary cutaneous mucormycosis: guide to surgical management. Ann Plast Surg 2002;49:385–390. 5. Burdick LM, Hamrock D, Mawhorter S et al. JAAD Grand Rounds quiz. Asymptomatic necrotic ulcer on leg. J Am Acad Dermatol 2009;61:172–174. 6. Rubin AI, Grossman ME. Bull’s-eye cutaneous infarct of zygomycosis: a bedside diagnosis confirmed by touch preparation. J Am Acad Dermatol 2004;51:996–1001. 7. Sankar J, Arun S, Sankar MJ et al. Primary cutaneous mucormycosis during induction chemotherapy in a child with acute lymphoblastic leukemia. Indian J Pediatr 2009;76: 1161–1163. Address correspondence to Ossama Abbas, M.D., Department of Dermatology, American University of Beirut Medical Center, P.O. Box-11-0236, Riad El Solh/Beirut 1107 2020, Beirut, Lebanon, or e-mail: [email protected].
8-YEAR-OLD GIRL areas and spindle cell fascicles, and the latter are not arranged parallel to the epidermis. Diffuse neurofibroma can be differentiated from dermatomyofibroma according to its S-100 positivity (1). Dermatomyofibroma is a benign tumor and does not tend to recur (3), so it is proposed that clinical follow-up without surgical excision is appropriate in some cases and may be considered in locations in which surgery could produce significant cosmetic defects (1).
References 1. Tardı´o JC, Herna´ndez-Nu´n˜ez A, Guzma´n A et al. Dermatomyofibromas presenting in pediatric patients: clinicopathologic characteristics and differential diagnosis. J Cutan Pathol 2011;38:967–972. 2. Go´mez-Moyano E, Vera-Casan˜o A, Martı´nez-Garcı´a S et al. Two cases of dermatomyofibroma (plaque-like dermal fibromatosis). Int J Dermatol 2010;49:914–917. 3. Gilaberte Y, Coscojuela C, Doste D et al. Dermatomyofibroma in a male child. J Eur Acad Dermatol Venereol 2005;19:257–259. 4. Rose C, Bro¨cker E-B. Dermatomyofibroma: case report and review. Pediatr Dermatol 1999;16:456–459. 5. Holst V, Junkins Hopkins J, Elenitsas K. Cutaneous smooth muscle neoplasms: clinical features, histologic findings, and treatment options. J Am Acad Dermatol 2002;46:477–490. 6. Viglizzo G, Occella C, Calonje E et al. A unique case of multiple dermatomyofibromas. Clin Dermatol 2008;33:622– 624. 7. Patrizi A, Vespignani MF, Rizzoli L et al. An asymptomatic abdominal nodule in a 5-year-old boy. Pediatr Dermatol 1999;16:154–156. Address correspondence to Magdalena Herna´ndez, M.D., Hospital Privado de Co´rdoba, Department of Dermatology, Naciones Unidas 364, Co´rdoba, Argentina, or e-mail: [email protected].
