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Extraocular sebaceous carcinoma: A clinicopathologic reassessment
3666
2960
Emerging use of skin biopsies in the diagnosis of neuronal ceroid lipofuscinosis Monica Valentin, MD, Georgetown University Hospital-Washington Hospital Center, Washington, DC, United States; Ohara Aivaz, MD, Georgetown University Hospital-Washington Hospital Center, Washington, DC, United States; Maura Caufield, MD, Georgetown University Hospital-Washington Hospital Center, Washington, DC, United States; Michael Cardis, MD, Georgetown University Hospital-Washington Hospital Center, Washington, DC, United States; Kaiane Habeshian, MD, Georgetown University HospitalWashington Hospital Center, Washington, DC, United States; Zetta Fayos, MD, Georgetown University Hospital-Washington Hospital Center, Washington, DC, United States; Arash Radfar, MD, Georgetown University Hospital-Washington Hospital Center, Washington, DC, United States Neuronal ceroid lipofuscinosis (NCL) are a group of severe inherited neurodegenerative lysosomal storage disorders that affect children and young adults. There are infantile, late infantile, juvenile and adult forms, all of which are characterized by the intracellular accumulation of autofluorescent ceroid lipopigments in neurons as well as other tissues. Clinical features include progressive global mental deterioration, motor abnormalities, vision loss from retinopathy, and epilepsy. In the past, the cornerstone of diagnosis was postmortem histopathologic examination of brain tissues. Currently, NCL diagnosis is based on clinical presentation, neuroimaging, and is confirmed by histopathology, enzymatic assay, and genetic testing. Although the latter may yield a definitive diagnosis, in select institutions and countries it may not be feasible. Electron microscopy examination of skin biopsies provides a costeffective, sensitive, and efficient alternative. Emerging reports of simple hematoxylineeosin staining (H&E) are even more promising as histopathology can demonstrate characteristic eosinophilic intracytoplasmic inclusions within the eccrine glands. These inclusions may also be highlighted on periodic acideSchiff stain (PAS). Thus, skin biopsies with H&E and PAS staining may become a useful minimally invasive tool in the diagnosis of NCL. Awareness of this entity is necessary as dermatopathologists will play a key role in aiding the diagnosis. We present a case of patient who presented to dermatology for an axillary biopsy after he was evaluated by his neurologist for ataxia, neuropathy, hyperkinetic involuntary movements, vision loss, mental slowness, and presumed NCL.
Expression of fascin, p53, and CD31 in inflammatory dermatoses with Langerhans cell hyperplasia and Langerhans cell histiocytosis Angela Sutton, DO, Saint Louis University, Department of Dermatology, St. Louis, MO, United States; Eric Armbrecht, PhD, Saint Louis University, St. Louis, MO, United States; Claudia Vidal, MD, PhD, Saint Louis University, Department of Dermatology, St. Louis, MO, United States; Ilana Rosman, MD, Washington University, Department of Dermatology, St. Louis, MO, United States; M. Yadira Hurley, MD, Saint Louis University, Department of Dermatology, St. Louis, MO, United States
Commercial support: None identified.
Background: Langerhans cell histiocytosis (LCH) is a proliferative disorder of Langerhans cells, and diagnosis is challenging both clinically and histologically. A potential diagnostic pitfall is distinguishing LCH from Langerhans cell hyperplasia, which is a benign reactive process that can occur in a variety of inflammatory skin disorders. Currently CD1a and S100 are considered specific markers of Langerhans cell histiocytosis, but these markers are positive in both cases of LCH and Langerhans cell hyperplasia. Prior studies have demonstrated positive staining of Fascin, p53, and CD31 in cases of LCH, but currently no studies have compared the staining profiles of these immunohistochemical markers between these two entities. Materials and methods: Cases of LCH and Langerhans cell hyperplasia were obtained from Saint Louis University and Washington University in Saint Louis, Missouri. CD1a, Fascin, CD31, and p53 immunohistochemical stains were completed on all cases. The stained specimens were then reviewed and interpreted by two board certified dermatopathologists (Y.H. and C.V.). Fascin, CD31, p53 were graded as a percentage of CD1a staining cells in the epidermis and dermis. Results: 15 cases of LCH and 15 cases of Langerhans cell hyperplasia were included in the study. Fascin showed no significant differences in staining between the two entities. CD31 was positive in the dermal infiltrate in 40% of cases of Langerhans cell histiocytosis and negative in all cases of Langerhans cell hyperplasia. P53 was positive in the epidermal infiltrate in 50% of cases of LCH, and positive in the dermal infiltrate in 93% of cases of LCH, while negative in all cases of Langerhans cell hyperplasia. Conclusions: Fascin was not a helpful marker in distinguishing Langerhans cell histiocytosis from Langerhans cell hyperplasia. CD31, if positive in the dermal infiltrate, is suggestive of a diagnosis of LCH, but exhibits a relatively low sensitivity for this purpose. P53 proved to be a helpful and accurate diagnostic immunohistochemical stain when distinguishing between LCH and Langerhans cell hyperplasia. Commercial support: None identified.
3887
2423
Erythema nodosum in the setting of everolimus use Sharon Kim, MD, The University of Texas Medical School - Houston, Houston, TX, United States; Leon Chen, MD, The University of Texas Medical School Houston, Houston, TX, United States; Adelaide Hebert, MD, The University of Texas Medical School - Houston, Houston, TX, United States; John Slopis, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; Mary Kay Koenig, MD, The University of Texas Medical School - Houston, Houston, TX, United States; Anisha Patel, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, United States Erythema nodosum (EN) is a hypersensitivity reaction in the subcutaneous fat that may be drug-induced. While some chemotherapeutic agents such as BRAF inhibitors have been associated with EN, there are no mTOR inhibitors including everolimus that have been linked to EN. We report two patients who developed erythema nodosum while on everolimus. A 25-year-old Hispanic male patient with a recurrent right temporal glioblastoma developed a skin eruption while undergoing therapy with everolimus. Initially, the patient took only vemurafenib without any cutaneous side effects. After receiving therapy for 16 months with vemurafenib, everolimus was added at a dose of 5 mg once daily. The patient then developed tender, firm, illdefined erythematous plaques and papules of the bilateral posterior thighs and left upper arm. These lesions were clinically diagnosed as erythema nodosum and the lesions resolved with drug holiday. Everolimus was reintroduced at a reduced dose of 2.5 mg once per day, and two weeks after restarting everolimus, the patient developed similar tender subcutaneous nodules on his left lower leg, bilateral upper extremities, and right buttock. The clinical picture was consistent with erythema nodosum. He was instructed to continue the everolimus as well as triamcinolone and ibuprofen as needed. A 35-year-old white female patient with neurofibromatosis I received everolimus 10 mg per day to potentially reduce the cutaneous lesions of her genetic disorder. After seventy days of therapy, the patient had firm red subcutaneous nodules that were both tender to touch and warm. The patient had no history of sore throat, infection or use of other new medications. Her clinical diagnosis was erythema nodosum and therapeutic intervention consisted of 325 mg aspirin up to four times per day. The lower extremity nodules and the discomfort began to dissipate within the first weeks of therapy and the patient was able to lower her aspirin dose to once daily while still maintaining her dosage of everolimus. While EN is a known side effect of BRAF inhibitors, drugs which are often used in combination with mTOR inhibitors, EN has not previously been reported with everolimus. Clinicians need to recognize that either BRAF inhibitors or everolimus are capable of inducing panniculitis, and that chemotherapy dose reduction or cessation is not necessarily indicated when erythema nodosum develops, particularly when responses to aspirin or NSAIDs is favorable.
Extraocular sebaceous carcinoma: A clinicopathologic reassessment Nicole M. Candelario, MD, Department of Dermatology University of Puerto Rico, San Juan, PR, United States; Julio E. Sanchez, MD, University of Puerto Rico, San Juan, PR, United States; Jorge L. Sanchez, MD, University of Puerto Rico, San Juan, PR, United States; Rafael F. Martin-Garcia, MD, University of Puerto Rico, San Juan, PR, United States; Nicole M. Rochet, MD, MS, University of Puerto Rico, San Juan, PR, United States Background: Sebaceous carcinoma is an aggressive adnexal neoplasm with sebaceous differentiation. Risk factors for its development include advancing age, Asian ethnicity, history of irradiation to the head and neck region, MuireTorre syndrome, and immunosuppression. Ocular sebaceous carcinomas refer to those neoplasms situated in the eyelid, and extraocular sebaceous carcinomas to those situated elsewhere in the skin. Extraocular sebaceous carcinoma is clinically and histopathologically different from ocular sebaceous carcinoma. Few reports have described the histopathologic characteristics of the sebaceous carcinoma occurring extraocularly. Hereby, we present the results of a retrospective study where the demographic data and the histopathologic characteristics of extraocular sebaceous carcinoma were evaluated.
Commercial support: None identified.
Commercial support: None identified.
AB98
J AM ACAD DERMATOL
Methods: Seventy-two cases of extraocular sebaceous carcinoma were identified from the database of a dermatopathology laboratory from January 1, 2007 to May 31, 2013. Histopathologic features were studied by analyzing the architectural pattern and cytopathologic attributes, namely the degree of cellular differentiation, cellular growth pattern, presence or absence of necrosis, ulceration, and pagetoid spread of neoplastic cells in the epidermis. The cellular growth pattern was classified as squamoid or basaloid. Results: More cases occurred in men (60%), with a mean age at diagnosis of 65.8 years (range 39-99 years). The majority of the tumors affected the head and neck areas (65%). Other affected areas included the back (19%), chest (7%), upper extremities (4%), lower extremities (3%) and the abdomen (1%). The neoplasms were histopathologically classified as well-differentiated (22%), moderately differentiated (67%), and poorly differentiated (11%). Sixty-seven percent (67%) of cases demonstrated a squamoid growth pattern and thirty-three percent (33%) demonstrated a basaloid growth pattern. A majority of the neoplasms histopathologically classified as well-differentiated (94%) and moderately differentiated (65%) demonstrated a squamoid growth pattern. Ten percent (10%) of cases exhibited cystic histopathologic changes and three of these cases had a confirmed diagnosis of MuireTorre syndrome. Conclusion: When compared with ocular sebaceous carcinoma, extraocular sebaceous carcinoma can be considered as a distinct clinicopathologic entity.
MAY 2016
2960
Emerging use of skin biopsies in the diagnosis of neuronal ceroid lipofuscinosis Monica Valentin, MD, Georgetown University Hospital-Washington Hospital Center, Washington, DC, United States; Ohara Aivaz, MD, Georgetown University Hospital-Washington Hospital Center, Washington, DC, United States; Maura Caufield, MD, Georgetown University Hospital-Washington Hospital Center, Washington, DC, United States; Michael Cardis, MD, Georgetown University Hospital-Washington Hospital Center, Washington, DC, United States; Kaiane Habeshian, MD, Georgetown University HospitalWashington Hospital Center, Washington, DC, United States; Zetta Fayos, MD, Georgetown University Hospital-Washington Hospital Center, Washington, DC, United States; Arash Radfar, MD, Georgetown University Hospital-Washington Hospital Center, Washington, DC, United States Neuronal ceroid lipofuscinosis (NCL) are a group of severe inherited neurodegenerative lysosomal storage disorders that affect children and young adults. There are infantile, late infantile, juvenile and adult forms, all of which are characterized by the intracellular accumulation of autofluorescent ceroid lipopigments in neurons as well as other tissues. Clinical features include progressive global mental deterioration, motor abnormalities, vision loss from retinopathy, and epilepsy. In the past, the cornerstone of diagnosis was postmortem histopathologic examination of brain tissues. Currently, NCL diagnosis is based on clinical presentation, neuroimaging, and is confirmed by histopathology, enzymatic assay, and genetic testing. Although the latter may yield a definitive diagnosis, in select institutions and countries it may not be feasible. Electron microscopy examination of skin biopsies provides a costeffective, sensitive, and efficient alternative. Emerging reports of simple hematoxylineeosin staining (H&E) are even more promising as histopathology can demonstrate characteristic eosinophilic intracytoplasmic inclusions within the eccrine glands. These inclusions may also be highlighted on periodic acideSchiff stain (PAS). Thus, skin biopsies with H&E and PAS staining may become a useful minimally invasive tool in the diagnosis of NCL. Awareness of this entity is necessary as dermatopathologists will play a key role in aiding the diagnosis. We present a case of patient who presented to dermatology for an axillary biopsy after he was evaluated by his neurologist for ataxia, neuropathy, hyperkinetic involuntary movements, vision loss, mental slowness, and presumed NCL.
Expression of fascin, p53, and CD31 in inflammatory dermatoses with Langerhans cell hyperplasia and Langerhans cell histiocytosis Angela Sutton, DO, Saint Louis University, Department of Dermatology, St. Louis, MO, United States; Eric Armbrecht, PhD, Saint Louis University, St. Louis, MO, United States; Claudia Vidal, MD, PhD, Saint Louis University, Department of Dermatology, St. Louis, MO, United States; Ilana Rosman, MD, Washington University, Department of Dermatology, St. Louis, MO, United States; M. Yadira Hurley, MD, Saint Louis University, Department of Dermatology, St. Louis, MO, United States
Commercial support: None identified.
Background: Langerhans cell histiocytosis (LCH) is a proliferative disorder of Langerhans cells, and diagnosis is challenging both clinically and histologically. A potential diagnostic pitfall is distinguishing LCH from Langerhans cell hyperplasia, which is a benign reactive process that can occur in a variety of inflammatory skin disorders. Currently CD1a and S100 are considered specific markers of Langerhans cell histiocytosis, but these markers are positive in both cases of LCH and Langerhans cell hyperplasia. Prior studies have demonstrated positive staining of Fascin, p53, and CD31 in cases of LCH, but currently no studies have compared the staining profiles of these immunohistochemical markers between these two entities. Materials and methods: Cases of LCH and Langerhans cell hyperplasia were obtained from Saint Louis University and Washington University in Saint Louis, Missouri. CD1a, Fascin, CD31, and p53 immunohistochemical stains were completed on all cases. The stained specimens were then reviewed and interpreted by two board certified dermatopathologists (Y.H. and C.V.). Fascin, CD31, p53 were graded as a percentage of CD1a staining cells in the epidermis and dermis. Results: 15 cases of LCH and 15 cases of Langerhans cell hyperplasia were included in the study. Fascin showed no significant differences in staining between the two entities. CD31 was positive in the dermal infiltrate in 40% of cases of Langerhans cell histiocytosis and negative in all cases of Langerhans cell hyperplasia. P53 was positive in the epidermal infiltrate in 50% of cases of LCH, and positive in the dermal infiltrate in 93% of cases of LCH, while negative in all cases of Langerhans cell hyperplasia. Conclusions: Fascin was not a helpful marker in distinguishing Langerhans cell histiocytosis from Langerhans cell hyperplasia. CD31, if positive in the dermal infiltrate, is suggestive of a diagnosis of LCH, but exhibits a relatively low sensitivity for this purpose. P53 proved to be a helpful and accurate diagnostic immunohistochemical stain when distinguishing between LCH and Langerhans cell hyperplasia. Commercial support: None identified.
3887
2423
Erythema nodosum in the setting of everolimus use Sharon Kim, MD, The University of Texas Medical School - Houston, Houston, TX, United States; Leon Chen, MD, The University of Texas Medical School Houston, Houston, TX, United States; Adelaide Hebert, MD, The University of Texas Medical School - Houston, Houston, TX, United States; John Slopis, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; Mary Kay Koenig, MD, The University of Texas Medical School - Houston, Houston, TX, United States; Anisha Patel, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, United States Erythema nodosum (EN) is a hypersensitivity reaction in the subcutaneous fat that may be drug-induced. While some chemotherapeutic agents such as BRAF inhibitors have been associated with EN, there are no mTOR inhibitors including everolimus that have been linked to EN. We report two patients who developed erythema nodosum while on everolimus. A 25-year-old Hispanic male patient with a recurrent right temporal glioblastoma developed a skin eruption while undergoing therapy with everolimus. Initially, the patient took only vemurafenib without any cutaneous side effects. After receiving therapy for 16 months with vemurafenib, everolimus was added at a dose of 5 mg once daily. The patient then developed tender, firm, illdefined erythematous plaques and papules of the bilateral posterior thighs and left upper arm. These lesions were clinically diagnosed as erythema nodosum and the lesions resolved with drug holiday. Everolimus was reintroduced at a reduced dose of 2.5 mg once per day, and two weeks after restarting everolimus, the patient developed similar tender subcutaneous nodules on his left lower leg, bilateral upper extremities, and right buttock. The clinical picture was consistent with erythema nodosum. He was instructed to continue the everolimus as well as triamcinolone and ibuprofen as needed. A 35-year-old white female patient with neurofibromatosis I received everolimus 10 mg per day to potentially reduce the cutaneous lesions of her genetic disorder. After seventy days of therapy, the patient had firm red subcutaneous nodules that were both tender to touch and warm. The patient had no history of sore throat, infection or use of other new medications. Her clinical diagnosis was erythema nodosum and therapeutic intervention consisted of 325 mg aspirin up to four times per day. The lower extremity nodules and the discomfort began to dissipate within the first weeks of therapy and the patient was able to lower her aspirin dose to once daily while still maintaining her dosage of everolimus. While EN is a known side effect of BRAF inhibitors, drugs which are often used in combination with mTOR inhibitors, EN has not previously been reported with everolimus. Clinicians need to recognize that either BRAF inhibitors or everolimus are capable of inducing panniculitis, and that chemotherapy dose reduction or cessation is not necessarily indicated when erythema nodosum develops, particularly when responses to aspirin or NSAIDs is favorable.
Extraocular sebaceous carcinoma: A clinicopathologic reassessment Nicole M. Candelario, MD, Department of Dermatology University of Puerto Rico, San Juan, PR, United States; Julio E. Sanchez, MD, University of Puerto Rico, San Juan, PR, United States; Jorge L. Sanchez, MD, University of Puerto Rico, San Juan, PR, United States; Rafael F. Martin-Garcia, MD, University of Puerto Rico, San Juan, PR, United States; Nicole M. Rochet, MD, MS, University of Puerto Rico, San Juan, PR, United States Background: Sebaceous carcinoma is an aggressive adnexal neoplasm with sebaceous differentiation. Risk factors for its development include advancing age, Asian ethnicity, history of irradiation to the head and neck region, MuireTorre syndrome, and immunosuppression. Ocular sebaceous carcinomas refer to those neoplasms situated in the eyelid, and extraocular sebaceous carcinomas to those situated elsewhere in the skin. Extraocular sebaceous carcinoma is clinically and histopathologically different from ocular sebaceous carcinoma. Few reports have described the histopathologic characteristics of the sebaceous carcinoma occurring extraocularly. Hereby, we present the results of a retrospective study where the demographic data and the histopathologic characteristics of extraocular sebaceous carcinoma were evaluated.
Commercial support: None identified.
Commercial support: None identified.
AB98
J AM ACAD DERMATOL
Methods: Seventy-two cases of extraocular sebaceous carcinoma were identified from the database of a dermatopathology laboratory from January 1, 2007 to May 31, 2013. Histopathologic features were studied by analyzing the architectural pattern and cytopathologic attributes, namely the degree of cellular differentiation, cellular growth pattern, presence or absence of necrosis, ulceration, and pagetoid spread of neoplastic cells in the epidermis. The cellular growth pattern was classified as squamoid or basaloid. Results: More cases occurred in men (60%), with a mean age at diagnosis of 65.8 years (range 39-99 years). The majority of the tumors affected the head and neck areas (65%). Other affected areas included the back (19%), chest (7%), upper extremities (4%), lower extremities (3%) and the abdomen (1%). The neoplasms were histopathologically classified as well-differentiated (22%), moderately differentiated (67%), and poorly differentiated (11%). Sixty-seven percent (67%) of cases demonstrated a squamoid growth pattern and thirty-three percent (33%) demonstrated a basaloid growth pattern. A majority of the neoplasms histopathologically classified as well-differentiated (94%) and moderately differentiated (65%) demonstrated a squamoid growth pattern. Ten percent (10%) of cases exhibited cystic histopathologic changes and three of these cases had a confirmed diagnosis of MuireTorre syndrome. Conclusion: When compared with ocular sebaceous carcinoma, extraocular sebaceous carcinoma can be considered as a distinct clinicopathologic entity.
MAY 2016