RESUMEN
BACKGROUND: Alpha-methylacyl-CoA racemase (AMACR), also known as P504S, is a protein that plays an important role in mitochondrial and peroxisomal beta-oxidation of branched-chain fatty acid and bile acid intermediates. AMACR has been established as a valuable diagnostic marker for prostate cancer and has recently been shown to be useful in the diagnosis of colorectal carcinoma. Despite the importance of lipid metabolism in sebum production by sebaceous glands of the skin, there are no studies evaluating the expression of AMACR in sebaceous neoplasms. METHODS: Five samples of normal sebaceous glands as well as five cases each of sebaceous hyperplasia (SH), sebaceous adenoma (SA), basal cell carcinoma (BCC) with sebaceous differentiation and extraocular sebaceous carcinoma (SC) were evaluated for immunohistochemical (IHC) expression of AMACR. Each case was reviewed by a single dermatopathologist and graded using a semi-objective grading schema. RESULTS: Normal sebaceous glands showed strong (4+) expression of AMACR. Among sebaceous neoplasms, SH showed the highest expression (4+), SA and BCC with sebaceous differentiation showed varied expression (2+ and 1+, respectively), and extraocular SC showed no expression of AMACR. CONCLUSIONS: The expression of AMACR is increased in benign sebaceous glands and SH; with decreasing AMACR expression in tumors with less sebaceous differentiation (i.e. SA and SC). These findings provide insight into the potential pathogenesis of sebaceous neoplasms while assisting in the microscopic distinction of SA from SC.
Asunto(s)
Adenoma/enzimología , Carcinoma/enzimología , Racemasas y Epimerasas/metabolismo , Neoplasias de las Glándulas Sebáceas/enzimología , Glándulas Sebáceas/enzimología , Adenoma/patología , Carcinoma/patología , Humanos , Hiperplasia/enzimología , Hiperplasia/patología , Inmunohistoquímica , Selección de Paciente , Neoplasias de las Glándulas Sebáceas/patología , Glándulas Sebáceas/patologíaRESUMEN
The pathophysiology of juvenile nasopharyngeal angiofibroma (JNA) has yet to be fully elucidated, but the influence of steroid hormones in their growth has been suggested. This neoplasm is known to afflict adolescent males. However, only a minority of the neoplastic cells express androgen receptors. The expression of estrogen receptor beta by the tumor cells recently has been demonstrated. Aromatase (P450) is an enzyme which is responsible for converting androgens to estrogens. However, the rule of aromatase in the pathogenesis of JNA is unknown. In this study we attempt to explain the hormone-induced growth theory by characterizing the aromatase (P450) in JNA. We examined five sinonasal JNA from adolescent males, all of which stained positive for aromatase. We propose that this enzyme is responsible for the local conversion of androgens into estrogens, which subsequently bind to the estrogen receptors leading to the growth of these tumors.
Asunto(s)
Angiofibroma/patología , Aromatasa/metabolismo , Neoplasias Nasofaríngeas/patología , Adolescente , Andrógenos/genética , Niño , Técnica del Anticuerpo Fluorescente Directa , Humanos , Inmunohistoquímica , Masculino , Receptores Androgénicos/metabolismo , Receptores de Estrógenos/metabolismoRESUMEN
CD5 is a 67 KD glycoprotein receptor that is present on a variety of T lymphocytes and mantle zone lymphocytes and is used routinely for the diagnosis of lymphomas and thymic carcinomas. That CD5 may be useful in diagnosis of mesenchymal tumors was an incidental finding in our sarcoma practice. This pilot study evaluated CD5 expression in benign and malignant muscle tumors in comparison to normal muscle. Search of our pathology database identified the following cases: leiomyomas (10), rhabdomyomas (3), leiomyosarcomas (33), and rhabdomyosarcomas (9). In some of these cases, non-neoplastic smooth muscle (10) and skeletal muscle (6) were identified adjacent to tumors. In addition, 3 cases were retrieved for non-neoplastic smooth muscle tissue that was unrelated to any tumor. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded tissue blocks using a CD5 monoclonal antibody. Positive immunoreactivity to CD5 was determined as 2+ (moderate) to 3+ (strong) cytoplasmic brown staining. CD5 was strongly and diffusely expressed in non-neoplastic skeletal (6/6) and smooth (10/10) muscle adjacent to tumor. Focal areas of moderate staining were sometimes observed. CD5 was also strongly and diffusely expressed in 3 cases of smooth muscle tissue not adjacent to tumor. Immunoreactivity to CD5 was negative in rhabdomyomas (3/3), rhabdomyosarcomas (9/9), and high-grade leiomyosarcomas (27/27 cases). Leiomyomas (10/10) were CD5 positive but showed variable intensity within the same tumor. Low-grade leiomyosarcomas (6/6) exhibited variable CD5 expression. In conclusion, this pilot study suggests that CD5 staining may be used to differentiate benign muscle tissue from malignancy. Albeit our case series is limited, this study indicates potential utility of CD5 staining in diagnosis of muscle tumors.
Asunto(s)
Antígenos CD5/análisis , Neoplasias de los Músculos/diagnóstico , Neoplasias de los Músculos/patología , Sarcoma/diagnóstico , Sarcoma/patología , Antígenos CD/análisis , Humanos , Inmunohistoquímica , Leiomioma/patología , Leiomiosarcoma/patología , Músculo Esquelético/citología , Músculo Esquelético/patología , Músculo Liso/citología , Músculo Liso/patología , Estudios Retrospectivos , Rabdomioma/patología , Rabdomiosarcoma/patología , Linfocitos T/patologíaRESUMEN
A 61-year-old female with a 4-year history of disseminated granuloma annulare was successfully treated with the antitumor necrosis factor (TNF)-alpha antibody, adalimumab. The patient had failed high potency topical glucocorticoids, hydroxychloroquine, and narrow-band ultraviolet light (UV)-B phototherapy. Anti-TNF-alpha therapy may be a therapeutic option in patients with disseminated granuloma annulare poorly controlled with conventional medications.
Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Granuloma Anular/tratamiento farmacológico , Adalimumab , Anticuerpos Monoclonales Humanizados , Biopsia , Femenino , Granuloma Anular/inmunología , Granuloma Anular/patología , Histiocitos/patología , Histiocitos/ultraestructura , Humanos , Persona de Mediana Edad , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
BACKGROUND: Bax-interacting factor-1 (Bif-1) binds to Bax, which in turn activates this proapoptotic protein. In the absence of Bif-1, the ability to induce apoptosis through the intrinsic pathway is greatly reduced. Merkel cell carcinoma (MCC) classically shows an aggressive behavior and lack of response to chemotherapy, which remains unexplained. Previous studies have documented the presence of Bax in MCC, but Bif-1 expression has not been evaluated. Herein, the expression of Bif-1 and Bax in cutaneous MCC is examined. MATERIALS AND METHODS: The immunohistochemical expression of Bif-1 and Bax protein was examined in nine cases of MCC. Both positive and negative controls were conducted. All the cases were reviewed by a single dermatopathologist. RESULTS: Bif-1 was detected in nine cases (100%), and Bax was expressed in six cases (66%). The percent positive cells for Bif-1 in MCC ranged from 85% to 98% positive (mean 93.9%). At the same time, decreased Bax expression was shown with 0-8% positive cells (mean 3.45%). CONCLUSION: The increased expression of Bif-1 in MCC is associated with low levels of Bax staining. These findings suggest that the upregulation of Bif-1 could in part be responsible for tumorigenesis in cutaneous MCC. As shown, Bax and Bif-1 expression are not exclusively antithetical; therefore, future studies evaluating the expression of both proteins should be conducted.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Carcinoma de Células de Merkel/metabolismo , Neoplasias Cutáneas/metabolismo , Proteína X Asociada a bcl-2/biosíntesis , Proteínas Adaptadoras Transductoras de Señales/genética , Anciano , Anciano de 80 o más Años , Apoptosis/fisiología , Carcinoma de Células de Merkel/genética , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/genética , Proteína X Asociada a bcl-2/genéticaRESUMEN
BACKGROUND: Survivin is a member of the inhibitor of apoptosis family of proteins implicated in the inhibition of apoptosis and cell cycle control, both crucial in the progression to malignancy. Survivin overexpression has been demonstrated in numerous malignancies including cutaneous squamous cell carcinoma and melanoma. To date, there are no studies evaluating the expression of survivin in sebaceous neoplasms. METHODS: Immunohistochemical expression of survivin was evaluated in a total of 20 extraocular sebaceous neoplasms: sebaceous hyperplasia (SH, 8), sebaceous adenoma (SA, 8), and sebaceous carcinoma (SC, 4). All the results were independently evaluated by a single dermatopathologist. RESULTS: Nuclear expression of survivin was present in 1.4% of lesional SH cells, 8.2% of SA cells, and 12.5% of SC cells. A significant difference in survivin expression with the Student t test was noted between SH and SA (P=0.01), SA and SC (P=0.05), and SH and SC (P=0.001). CONCLUSIONS: There is a statistically significant difference in survivin expression among SH, SA, and SC. These findings demonstrate the potential diagnostic utility of survivin, further assisting in the microscopic differentiation of benign and malignant sebaceous neoplasms. However, larger studies are needed to determine the significance of survivin expression as it relates to recurrence, metastatic potential, and outcome.
Asunto(s)
Adenocarcinoma Sebáceo/metabolismo , Adenoma/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Neoplasias de las Glándulas Sebáceas/metabolismo , Glándulas Sebáceas/metabolismo , Glándulas Sebáceas/patología , Adenocarcinoma Sebáceo/diagnóstico , Adenocarcinoma Sebáceo/patología , Adenoma/diagnóstico , Adenoma/patología , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Núcleo Celular/metabolismo , Diagnóstico Diferencial , Femenino , Humanos , Hiperplasia/diagnóstico , Hiperplasia/metabolismo , Hiperplasia/patología , Proteínas Inhibidoras de la Apoptosis/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias de las Glándulas Sebáceas/diagnóstico , Neoplasias de las Glándulas Sebáceas/patología , SurvivinRESUMEN
Neurocrest-derived tissues express muscarinic and nicotinic acetylcholine receptors (mAChR and nAChR respectively). These receptors are critical for migration of neurocrest-derived cells to their corresponding tissues during development. Recent reports demonstrate neurocrest-derived melanoma and numerous non-Merkel cell neuroendocrine tumors express both muscarinic and nicotinic receptors. In light of the controversy surrounding the origin and pathogenesis of Merkel cell carcinoma (MCC), we investigated the immunohistochemical expression of both mAChR and nAChR in MCC. Fifteen cases of primary non-metastatic cutaneous MCC archived at a large veterans' hospital and tertiary referral dermatopathology service were retrieved by computer-assisted search. Immunohistochemistry was utilized to evaluate the presence of M3, M5 and beta 2 nAChR expression. All the cases were confirmed prior to study by a single board certified dermatopathologist (MBM). Fifteen cases of primary cutaneous MCC were diffusely positive for M3 and M5 mAChR staining. All cases lacked immunohistochemical staining for the beta 2 nAChR. Despite the limited number of cases, MCC appears to uniformly express M3 and M5 receptors. These receptors have been linked to cell proliferation and migration which may confer a potential therapeutic target.
Asunto(s)
Carcinoma de Células de Merkel/metabolismo , Receptores Muscarínicos/biosíntesis , Receptores Nicotínicos/biosíntesis , Neoplasias Cutáneas/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
The primitive neuroectodermal tumor (PNET)/Ewing family of tumors (EFT) and desmoplastic small round cell tumor (DSRCT) portend a grave prognosis. Ongoing research in similar neurocrest-derived neoplasms has implicated both the muscarinic acetylcholine receptor (mAChR) and nicotinic acetylcholine receptor (nAChR) in the pathogenesis of these neoplasms. Acetylcholine has been reported to impart a modulatory effect on chemotaxis and proliferation, an effect ameliorated by anticholinergic drugs. The aim of our study is to characterize the pattern of expression of mAChR and nAChR in PNET/EFT and DSRCT, in hopes of discovering a potential target for therapeutic improvements. We examined 34 cases of PNET/EFT and 2 DSRCT retrospectively by immunohistochemical studies. We found that AChRs are overexpressed in a significant number of PNET/EFT and DSRCT. The Western blot analysis of 3 human Ewing sarcoma cell lines confirms the presence of AChRs. Future studies are planned to confirm these results as well as to investigate their potential therapeutic implications.
Asunto(s)
Neoplasias Óseas/metabolismo , Neoplasias Encefálicas/metabolismo , Tumores Neuroectodérmicos Primitivos/metabolismo , Receptores Muscarínicos/metabolismo , Receptores Nicotínicos/metabolismo , Sarcoma de Ewing/metabolismo , Sarcoma de Células Pequeñas/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Western Blotting , Neoplasias Óseas/patología , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Niño , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Tumores Neuroectodérmicos Primitivos/patología , Estudios Retrospectivos , Sarcoma de Ewing/patología , Sarcoma de Células Pequeñas/patología , Análisis de Matrices TisularesRESUMEN
Atypical fibroxanthoma (AFX) is a spindle cell neoplasm of the skin seen typically on sun-damaged skin of the elderly. Though described as a benign entity, local recurrence and distant metastasis have been reported. This study aims to investigate the potential pathogenic role of CD117, the c-kit receptor in AFX. CD117 was detected in 15 of the 16 cases (94%). The percentage of positive cells for CD117 expression among all tumors was approximately 30%. CD117 proved to be a very sensitive marker of AFX. This antibody may be a useful diagnostic adjunct in AFX.
Asunto(s)
Biomarcadores de Tumor/análisis , Histiocitoma Fibroso Benigno/metabolismo , Proteínas Proto-Oncogénicas c-kit/biosíntesis , Neoplasias Cutáneas/metabolismo , Anciano , Anciano de 80 o más Años , Histiocitoma Fibroso Benigno/patología , Humanos , Inmunohistoquímica , Masculino , Neoplasias Cutáneas/patologíaRESUMEN
Perivascular epithelioid cell (PEC) tumors, also called 'PEComas,' are distinct tumors showing PEC differentiation with characteristic histologic and immunophenotypic features. PEComas are rare tumors documented in the literature presenting in numerous anatomic sites including the thorax, abdomen, pelvis, soft tissue and skin. Criteria for malignancy does not exist for the subset of PEComas that pursue an aggressive clinical course. Herein, we present an unusual case of a malignant PEC tumor presenting as a scalp nodule in a patient with a prior diagnosis of 'melanoma' based upon the immunophenotypic profile of an excised enlarged cervical lymph node. The purpose of this case presentation is to further describe the rare clinical manifestations of a subcutaneous PEC tumor, emphasize the malignant potential of this entity, and review the literature focusing upon clinicopathologic features of cutaneous/subcutaneous PEComas.
Asunto(s)
Células Epitelioides/patología , Neoplasias de los Tejidos Conjuntivo y Blando/diagnóstico , Tumor de Músculo Liso/diagnóstico , Anciano , Biomarcadores de Tumor/metabolismo , Diagnóstico Diferencial , Células Epitelioides/metabolismo , Humanos , Ganglios Linfáticos/patología , Masculino , Melanoma/diagnóstico , Melanoma/secundario , Neoplasias de los Tejidos Conjuntivo y Blando/metabolismo , Cuero Cabelludo/metabolismo , Cuero Cabelludo/patología , Neoplasias Cutáneas/diagnóstico , Tumor de Músculo Liso/metabolismo , Tumor de Músculo Liso/secundarioRESUMEN
BACKGROUND: Epidermal growth factor receptor (EGFR) and HER2, members of the Erb family of transmembrane receptor tyrosine kinases (RTK), are responsible for communicating extracellular signals to the nucleus. Moreover, EGFR and HER2 are implicated in tumorgenesis. Immunohistochemical studies have demonstrated that approximately 80% of cutaneous squamous cell carcinomas (SCC) express EGFR. To date, the expression of EGFR and HER2 has not been evaluated in primary cutaneous spindle squamous cell carcinoma (SSC). In extracutaneous spindle squamous cell carcinoma, there is evidence implicating the expression of RTK as a strong, independent prognostic indicator of potentially poor outcome. The purpose of this study is to investigate the expression of EGFR and HER2 in SSC, using immunohistochemical methods. MATERIALS AND METHODS: Thirteen cases of primary nonmetastatic cutaneous SSC archived at a large veterans' hospital and tertiary referral dermatopathology service were retrieved via a computer-assisted search. Immunohistochemistry was used to evaluate the presence of EGFR and/or HER2 expression. All cases were confirmed before study by a single, board-certified dermatopathologist. RESULTS: All 13 cases (100%) evaluated for the presence of HER2 were nonimmunoreactive for the receptor. Only one of the 13 cases (<8%) stained positive for EGFR. CONCLUSIONS: In several malignancies, the overexpression EGFR and HER2 is associated with clinically aggressive behavior. Despite a limited sample size, EGFR and HER2 are not overexpressed in SSC; this is cognate with the current opinion that SSC possesses limited metastatic potential. With prior reports demonstrating that approximately 80% of cutaneous SCC express EGFR, the negative expression of EGFR and HER2 in SSC presents the potential variable nature of the histologic subtypes of SCC, which can have prognostic and therapeutic implications.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Receptores ErbB/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Cutáneas/metabolismo , Anciano , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias Cutáneas/patologíaRESUMEN
Chromoblastomycosis is an uncommon chronic fungal infection capable of presenting in a variety of clinical guises. Herein, we present the histopathological features of an unusual dermal response engendered by this organism, consisting of dermal effacement by a spindle cell proliferation arranged in sweeping fascicles.
Asunto(s)
Cromoblastomicosis/diagnóstico , Fibroma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Proliferación Celular , Cromoblastomicosis/metabolismo , Diagnóstico Diferencial , Fibroma/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Sarcoma/diagnóstico , Neoplasias Cutáneas/metabolismoRESUMEN
BACKGROUND: The diagnosis of Merkel cell carcinoma (MCC) can be rather challenging; therefore, the immunohistochemical profile is important in confirming the microscopic diagnosis. Characteristic of the neuroendocrine and epithelial differentiation of MCC, antibodies to cytokeratin (CK) 20, CK7, epithelial membrane antigen, and neuron-specific enolase among others, are used in confirming the diagnosis. As reported in the literature, the majority of MCC express CK20 and are CK7 negative. Herein, we present a case series of seven patients with CK20-/CK7+ primary cutaneous neuroendocrine carcinoma. METHODS: All cases of MCC with specific CK20-/CK7+ staining on file at a large Veterans' hospital and tertiary referral dermatopathology service were reviewed. All seven cases were analyzed for clinical, pathologic and immunophenotypic attributes. All specimens were submitted for immunohistochemical staining and interpreted by a single dermatopathologist. RESULTS: All the cases showed diffuse cytoplasmic staining for CK7 and positive staining for synaptophysin. CK20 and thyroid transcription factor-1 staining was negative. CONCLUSIONS: Herein we have presented a hitherto unreported group of patients with CK20-/CK7+ primary neuroendocrine carcinoma of the skin. The purpose of this case series is to describe a new immunophenotypic variant of MCC, while further expanding the differential diagnosis of tumors included in the subset of neoplasms showing CK20-/CK7+ staining.
Asunto(s)
Carcinoma de Células de Merkel/metabolismo , Carcinoma de Células de Merkel/patología , Queratina-20/metabolismo , Queratina-7/metabolismo , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Anciano , Biomarcadores de Tumor/análisis , Femenino , Humanos , Inmunohistoquímica , Inmunofenotipificación , Masculino , Persona de Mediana EdadRESUMEN
Glucocorticoids are used clinically to treat a variety of inflammatory diseases including endotoxemia. We hypothesized that injecting mice with the steroid prednisolone (pred) would mitigate the enhanced bone marrow (BM) natural suppressor (NS) cell activity that occurs in mice after receiving an injection of lipopolysaccharide (LPS). In vitro, prednisolone blocked the ability of NS cells to produce the immunosuppressive molecule nitric oxide (NO) and also the ability to suppress T cell proliferation. Prednisolone acted both indirectly, by blocking synthesis of cytokines necessary for NS cell activation, and also directly on NS cells, by blocking production of NO. In vivo, variable results were obtained. Prednisolone at 20 microg/gm did decrease NS activity when injected into normal mice. However, when mice were injected with both LPS and prednisolone (0.2 or 20 microg/gm), a large increase in BM NS activity was observed. The increase was evident in both the ability of the BM cells to suppress T cell proliferation and to produce NO. The data show that, in vivo, the steroid prednisolone in conjunction with the inflammatory compound LPS act to enhance BM NS activity.