RESUMO
Folliculotropic metastasis of cutaneous melanoma is rare, with only 5 published case reports in the English language literature since it was first described in 2009. We report a 41-year-old man with a primary cutaneous melanoma of the right upper preauricular region with metastatic spread to the parotid gland and pulmonary lymph nodes. Excision of the primary lesion was performed and immunotherapy was initiated. Sixteen months later, the patient presented with 2 new lesions of the left forehead and left neck. Histopathological examination was consistent with folliculotropic dermal deposits of metastatic melanoma. Deeper sectioning into the blocks revealed only sparse perifollicular pigment deposition and rare dermal melanocytes-a potential diagnostic pitfall had this been seen in the initial sections. This case represents the sixth and youngest patient to date with folliculotropic metastatic melanoma. This entity often presents in patients with advanced disease, including increased Breslow thickness and/or multiple metastases to lymph nodes, internal organs, or both. The folliculotropic metastases tend to be small and are often multiple. The precise relationship between folliculotropic primary melanoma and folliculotropic metastasis is unclear. In one reported case and in our patient, the primary tumor was noted to have a "folliculocentric" pattern. Because of the latter finding, the differential diagnosis includes multiple primary folliculotropic melanomas. Thus, clinical correlation and knowledge concerning the evolution of disease in the patient are critical. This case highlights a rare and unusual pattern of metastatic melanoma and potential problems in differential diagnosis.
Assuntos
Doenças do Cabelo/patologia , Folículo Piloso/patologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adulto , Humanos , Masculino , Melanoma Maligno CutâneoRESUMO
BACKGROUND: The distinction between dermatofibroma (DF), dermatofibrosarcoma protuberans (DFSP), and other benign and malignant cutaneous spindle cell lesions frequently requires immunohistochemical staining. CD34 and factor XIIIa are the most commonly used immunostains; however, they may exhibit aberrant expression and introduce the potential for misdiagnosis. There is some data supporting that p75 and S100A6 may be additional helpful immunohistochemical markers. METHODS: We undertook a large case series examining the use of CD34 and factor XIIIa as well as p75 and S100A6 in DF, cellular DF, DFSP, indeterminate fibrohistiocytic lesion, and scar. RESULTS: As expected, CD34 stained DFSP, although it was usually negative in DF. Factor XIIIa was generally positive in DF and negative in DFSP. There were exceptions in both cases of DF and DFSP. S100A6 was routinely negative in all entities studied. P75 was negative in all cases except DFSP, approximately half of which showed weak and/or patchy positivity. CONCLUSIONS: We conclude that to date, CD34 and factor XIIIa remain the most reliable immunohistochemical markers for DF and DFSP.
Assuntos
Biomarcadores Tumorais/análise , Dermatofibrossarcoma/diagnóstico , Histiocitoma Fibroso Benigno/diagnóstico , Neoplasias Cutâneas/diagnóstico , Antígenos CD34/análise , Diagnóstico Diferencial , Fator XIIIa/análise , Humanos , Imuno-Histoquímica , Proteínas do Tecido Nervoso/análise , Receptores de Fator de Crescimento Neural/análise , Proteínas S100/análiseRESUMO
Cutaneous metastasis from cholangiocarcinoma is an extremely rare event. Herein, we present three cases with review of the literature. Case 1 is that of a young female with scalp metastasis. Cases 2 and 3 involve cutaneous metastasis to the sites of prior biliary drains, one occurring in a young female with a history of multiple biliary surgeries and one in a male with a history of sclerosing cholangitis. Review of the literature shows that the presentation of cutaneous metastases from cholangiocarcinoma can vary in terms of anatomic location and clinical features. The pathological and immunohistochemical profile of metastatic cholangiocarcinoma can be non-specific, and accurate diagnosis relies in part on clinical correlation. In summary, metastatic disease should always be included in the differential diagnosis of cutaneous lesions in patients with known malignancy.
Assuntos
Recidiva Local de Neoplasia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/secundário , Carcinoma/patologia , Carcinoma/terapia , Feminino , Humanos , Neoplasias do Seio Maxilar/patologia , Neoplasias do Seio Maxilar/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Cutâneas/terapia , Fatores de TempoRESUMO
Following B-cell antigen receptor (BCR) ligation, the cytoplasmic domains of immunoglobulin alpha (Ig alpha) and Ig beta recruit Syk to initiate signaling cascades. The coupling of Syk to several distal substrates requires linker protein BLNK. However, the mechanism by which BLNK is recruited to the BCR is unknown. Using chimeric receptors with wild-type and mutant Ig alpha cytoplasmic tails we show that the non-immunoreceptor tyrosine-based activation motif (ITAM) tyrosines, Y176 and Y204, are required to activate BLNK-dependent pathways. Subsequent analysis demonstrated that BLNK bound directly to phospho-Y204 and that fusing BLNK to mutated Ig alpha reconstituted downstream signaling events. Moreover, ligation of the endogenous BCR induced Y204 phosphorylation and BLNK recruitment. These data demonstrate that the non-ITAM tyrosines of Ig alpha couple Syk activation to BLNK-dependent pathways.
Assuntos
Antígenos CD/metabolismo , Proteínas de Transporte/metabolismo , Fosfoproteínas/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Antígenos CD/genética , Antígenos CD79 , Proteínas de Transporte/química , Proteínas de Transporte/genética , Células Clonais , Precursores Enzimáticos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Isoenzimas/metabolismo , Camundongos , Modelos Moleculares , Mutação , Fosfolipase C gama , Fosfoproteínas/química , Fosfoproteínas/genética , Proteínas Tirosina Quinases/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores de Antígenos de Linfócitos B/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais , Quinase Syk , Fosfolipases Tipo C/metabolismo , Domínios de Homologia de srcRESUMO
BACKGROUND: Multicentric reticulohistiocytosis (MRH) is a rare disease of uncertain etiology that most commonly presents as a papulonodular cutaneous eruption accompanied by erosive polyarthritis. Although MRH is considered a systemic disorder in that it targets skin and joints, involvement of thoracic and visceral organs is uncommon. OBSERVATIONS: A woman presented with diffuse cutaneous nodules, and skin biopsy findings revealed classic features of MRH. However, she also manifested severe pulmonary symptoms. A lung biopsy specimen showed prominent histiocytic infiltrates exhibiting the same characteristic morphologic features as those seen in her skin. Furthermore, the lung biopsy findings were significant for a pattern of usual interstitial pneumonia accompanied by notable lymphoid aggregates, a pattern of interstitial lung disease typical of systemic autoimmune and inflammatory conditions. CONCLUSIONS: These findings are notable because a histiocytic pulmonary infiltrate suggestive of direct pulmonary involvement by MRH is a rare event. In addition, presentation of MRH in the setting of usual interstitial pneumonia is unique. These observations document a new clinical and histopathologic presentation of MRH that is significant for expanding the idea of MRH as a systemic disease while supporting the notion that MRH is promoted by an inflammatory milieu.
Assuntos
Histiocitose/complicações , Histiocitose/diagnóstico , Fibrose Pulmonar Idiopática/etiologia , Dermatopatias/etiologia , Artrite/complicações , Diagnóstico Diferencial , Feminino , Humanos , Fibrose Pulmonar Idiopática/patologia , Pessoa de Meia-Idade , Dermatopatias/patologiaAssuntos
Papulose Linfomatoide/diagnóstico , Neoplasias Cutâneas/diagnóstico , Pele/patologia , Antibacterianos/uso terapêutico , Anticorpos Antinucleares/sangue , Pré-Escolar , Eritromicina/uso terapêutico , Exantema/etiologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Papulose Linfomatoide/sangue , Papulose Linfomatoide/tratamento farmacológico , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
Prophylactic fresh-frozen plasma (FFP) transfusion is often undertaken in hemodynamically stable patients with a minimally elevated international normalized ratio (INR) prior to invasive procedures, despite little evidence in support of this practice. The authors review the current literature in an attempt to clarify best clinical practice with regard to this issue. Although the activated partial thromboplastin time and prothrombin time-INR are useful laboratory tests to measure specific clotting factors in the coagulation cascade, in the absence of active bleeding or a preexisting coagulopathy, their utility as predictors of overall bleeding risk is limited. Several studies have shown an imperfect correlation between mild elevations in the INR and subsequent bleeding tendency. Furthermore, FFP transfusion is not always sufficient to achieve normal INR values in patients who have mild elevations (< 2) to begin with. Finally, there are risks associated with FFP transfusion, including potential transfusion-associated [disease] exposures as well as the time delay imposed by laboratory testing and transfusion administration prior to initiation of procedures. The authors propose that the current concept of a "normal" INR value warrants redefinition to make it a more meaningful clinical tool. Based on their review of the literature, the authors suggest that in a hemodynamically stable patient population there is a range of mildly prolonged INR values for which FFP transfusion is not beneficial, and is potentially harmful.
Assuntos
Transfusão de Sangue/estatística & dados numéricos , Coeficiente Internacional Normatizado , Procedimentos Neurocirúrgicos/métodos , Fator VIIa/uso terapêutico , Hemostasia Cirúrgica , Humanos , Tempo de Tromboplastina Parcial , Plasma , Tempo de Protrombina , Proteínas Recombinantes/uso terapêuticoRESUMO
V(D)J recombination is a tightly controlled process of somatic recombination whose regulation is mediated in part by chromatin structure. Here, we report that RAG2 binds directly to the core histone proteins. The interaction with histones is observed in developing lymphocytes and within the RAG1/RAG2 recombinase complex in a manner that is dependent on the RAG2 C terminus. Amino acids within the plant homeo domain (PHD)-like domain as well as a conserved acidic stretch of the RAG2 C terminus that is considered to be a linker region are important for this interaction. Point mutations that disrupt the RAG2-histone association inhibit the efficiency of the V(D)J recombination reaction at the endogenous immunoglobulin locus, with the most dramatic effect in the V to DJ(H) rearrangement.