RESUMO
BACKGROUND: Calciphylaxis is a life-threatening cutaneous ulcerative/necrotic disease characterized by vascular calcification/occlusion. It occurs most commonly in end-stage kidney disease (ESKD), known as uraemic calciphylaxis (UC) but can also occur in patients with chronic kidney disease (CKD) and normal kidney function (nonuraemic calciphylaxis; NUC). There are few large series of NUC in the literature. AIM: To compare the clinicopathological features of UC and NUC. METHODS: We retrospectively compared the clinicopathological features of 35 patients with NUC during the period 2010-2020 with those of 53 patients with UC (control group). Cases were classified as NUC in the absence of all of the following: ESKD, significant CKD (defined as serum creatinine > 3 mg/dL or creatinine clearance < 15 mL/min) and acute kidney injury requiring kidney replacement therapy or kidney transplantation. RESULTS: NUC represented 40% of the total cases, and there was a higher number of women (P < 0.01) and a higher median body mass index (P = 0.06) compared with the control UC group. Elevated parathyroid hormone was present in 44% of patients with NUC. Most of the tested patients were positive for lupus anticoagulants (56%). NUC biopsies showed a higher rate of extravascular calcium deposits (73% vs. 47%, P = 0.03). Dermal reactive vascular proliferation was the most common dermal change (32%). CONCLUSIONS: NUC is more common than previously reported and shows a higher predilection for obese postmenopausal women. Undiagnosed hyperparathyroidism shows a possible association with NUC. Lupus anticoagulants were positive in most patients. NUC biopsies are more likely than UC biopsies to display extravascular calcium deposition.
Assuntos
Calciofilaxia , Falência Renal Crônica , Insuficiência Renal Crônica , Calciofilaxia/diagnóstico , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Fatores de RiscoRESUMO
We have previously demonstrated that the EP1 subtype of PGE2 receptor is expressed in the differentiated compartment of normal human epidermis and is coupled to intracellular calcium mobilization. We therefore hypothesized that the EP1 receptor is coupled to keratinocyte differentiation. In in vitro studies, radioligand binding, RT-PCR, immunoblot and receptor agonist-induced second messenger studies demonstrate that the EP1 receptor is up-regulated by high cell density in human keratinocytes and this up-regulation precedes corneocyte formation. Moreover, two different EP1 receptor antagonists, SC51322 and AH6809, both inhibited corneocyte formation. SC51322 also inhibited the induction of differentiation-specific proteins, cytokeratin K10 and epidermal transglutaminase. We next examined the immunolocalization of the EP1 receptor in non-melanoma skin cancer in humans. Well-differentiated SCCs exhibited significantly greater membrane staining, while spindle cell carcinomas and BCCs had significantly decreased membrane staining compared with normal epidermis. This data supports a role for the EP1 receptor in regulating keratinocyte differentiation.
Assuntos
Diferenciação Celular , Queratinócitos/citologia , Queratinócitos/metabolismo , Receptores de Prostaglandina E/classificação , Receptores de Prostaglandina E/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Animais , Cálcio/metabolismo , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Receptores de Prostaglandina E/antagonistas & inibidores , Receptores de Prostaglandina E/biossíntese , Receptores de Prostaglandina E Subtipo EP1 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Células Tumorais Cultivadas , Xantonas/farmacologiaRESUMO
Squamous cell carcinoma (SCC) is the most common skin cancer in patients receiving immunosuppressive therapy, and is well documented to occur in patients that have undergone either solid organ transplantation or conventional myeloablative bone marrow transplantation. Nonmyeloablative hematopoietic cell transplantation (NMAT) provides transient, intensive immunosuppression, permitting allogeneic engraftment without ablating the marrow. The purpose of this report is to describe six patients that developed SCC (n=3), basal cell carcinoma (n=2), or malignant melanoma (n=2) over a period of 2-26 months following NMAT. All patients had myelodysplasia or acute myelogenous leukemia prior to transplantation. The authors demonstrate for the first time that patients who undergo NMAT are at risk for developing skin cancers and emphasize the need for close surveillance in the post transplantation period.
Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Melanoma , Síndromes Mielodisplásicas , Segunda Neoplasia Primária , Neoplasias Cutâneas , Condicionamento Pré-Transplante , Transplante Homólogo , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Fatores de Risco , Condicionamento Pré-Transplante/efeitos adversosRESUMO
There is a prevailing view that leiomyomas of deep soft tissue are rare or nonexistent, but there are limited data on this subject in the form of large clinical studies with long follow-up information. We reviewed 36 consultation cases that had been diagnosed as leiomyoma or probable leiomyoma based on absence of nuclear atypia, necrosis, and no/minimal mitotic activity. Follow-up information was obtained to determine whether these stringent histologic criteria could identify a biologically benign group of smooth muscle tumors of deep soft tissue. The tumors occurred in two distinct locations. The first (n = 13) occurred in deep somatic soft tissue of the lower extremity (7), upper extremity (2), trunk (2), axilla (1), and back (1) and affected the sexes equally (7 male, 6 female). Composed of a circumscribed mass of mature smooth muscle cells, they were frequently calcified with a mean mitotic activity of <1 mitosis/50 high power fields (HPF) (range 1-4 mitoses/50 HPF). Estrogen receptor and progesterone receptor proteins were negative in the three cases tested. No tumors recurred or metastasized (mean follow-up 58.7 months, range 5-97 months). The second group (n = 23) occurred within the retroperitoneum (20) or abdominal cavity (3) of women (1 male, 22 female). Resembling uterine leiomyomas, they were always distinct from the uterus, occasionally multiple (n = 4), and sometimes occurred up to years after hysterectomy (n = 3). Four cases occurred with synchronous uterine leiomyomas. In the six cases tested, five of six were positive for the estrogen receptor protein and all were positive for progesterone receptor protein. Mean mitotic activity was 1 mitosis/50 HPF (range <1-10 mitoses/50 HPF). None developed metastasis within the follow-up period (mean 42.5 months, range 6-120 months); one tumor with a positive margin recurred at 10 months. We conclude that clinically benign smooth muscle tumors of deep soft tissue are rare but can be identified using stringent histologic criteria. They comprise two distinct subtypes: leiomyomas of somatic soft tissue and retroperitoneal-abdominal leiomyomas. The latter probably arise from hormonally sensitive smooth muscle. Although similar to uterine leiomyomas, they are located at sites removed from the uterus and are likely independent soft tissue primaries rather than parasitic leiomyomas of the uterus. We suggest that these two groups of smooth muscle tumors be diagnostically approached in a site-specific fashion.
Assuntos
Leiomioma/patologia , Receptores de Estrogênio , Tumor de Músculo Liso/patologia , Neoplasias de Tecidos Moles/patologia , Adolescente , Adulto , Idoso , Proteínas de Transporte/análise , Criança , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Leiomioma/química , Leiomioma/classificação , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Receptores de Progesterona/análise , Tumor de Músculo Liso/química , Tumor de Músculo Liso/classificação , Neoplasias de Tecidos Moles/química , Neoplasias de Tecidos Moles/classificaçãoAssuntos
Artroplastia de Quadril , Neoplasias Femorais/patologia , Histiocitoma Fibroso Benigno/patologia , Neoplasias Primárias Desconhecidas/patologia , Osteossarcoma/patologia , Idoso , Feminino , Neoplasias Femorais/secundário , Cabeça do Fêmur , Histiocitoma Fibroso Benigno/secundário , Humanos , Masculino , Pessoa de Meia-Idade , Osteíte Deformante/patologia , Osteorradionecrose/patologia , Osteossarcoma/secundário , Fatores de RiscoRESUMO
A 4-year-old boy presented with a 6-month history of a red papule on the nasal septum. Physical examination was otherwise unremarkable. A biopsy specimen showed an epithelioid sarcoma characterized by nodular collections of epithelioid tumor cells with central, tumor cell necrosis. By immunohistochemistry the tumor cells were positive for cytokeratin, epithelial membrane antigen, vimentin, and CD34, but negative for S-100, CD31, factor VIII-related antigen, CD68, actin, desmin and myoglobin. Epithelioid sarcoma is an uncommon tumor of uncertain histogenesis that typically arises in the extremities of young adults. Both the age of our patient and the location of his tumor are unusual, emphasizing the spectrum of presentations that may occur with epithelioid sarcoma. Epithelioid sarcoma should be considered in the differential diagnosis of granulomatous diseases and epithelioid tumors of children, even in unusual locations.
Assuntos
Sarcoma/patologia , Neoplasias Cutâneas/patologia , Antígenos CD34/análise , Biomarcadores Tumorais/análise , Pré-Escolar , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Queratinas/análise , Masculino , Mucina-1/análise , Proteínas de Neoplasias/análise , Nariz , Sarcoma/química , Neoplasias Cutâneas/química , Vimentina/análiseRESUMO
Cyclooxygenase-2 (COX-2) expression is up-regulated in several types of human cancers and has also been directly linked to carcinogenesis. To investigate the role of COX-2 in pancreatic cancer, we evaluated COX-2 protein expression in primary human pancreatic adenocarcinomas (n = 23) and matched normal adjacent tissue (n = 11) by immunoblot analysis. COX-2 expression was found to be significantly elevated in the pancreatic tumor specimens compared with normal pancreatic tissue. To examine whether the elevated levels of COX-2 protein observed in pancreatic tumors correlated with the presence of oncogenic K-ras, we determined the K-ras mutation status in a subset of the tumors and corresponding normal tissues. The presence of oncogenic K-ras did not correlate with the level of COX-2 protein expressed in the pancreatic adenocarcinomas analyzed. These observations were also confirmed in a panel of human pancreatic tumor cell lines. Furthermore, in the pancreatic tumor cell line expressing the highest level of COX-2 (BxPC-3), COX-2 expression was demonstrated to be independent of Erk1/2 activation. The lack of correlation between COX-2 and oncogenic K-ras expression suggests that Ras activation may not be sufficient to induce COX-2 expression in pancreatic tumor cells and that the aberrant activation of signaling pathways other than Ras may be required for up-regulating COX-2 expression. We also report that the COX inhibitors sulindac, indomethacin and NS-398 inhibit cell growth in both COX-2-positive (BxPC-3) and COX-2-negative (PaCa-2) pancreatic tumor cell lines. However, suppression of cell growth by indomethacin and NS-398 was significantly greater in the BxPC-3 cell line compared with the PaCa-2 cell line (P = 0.004 and P < 0.001, respectively). In addition, the three COX inhibitors reduce prostaglandin E(2) levels in the BxPC-3 cell line. Taken together, our data suggest that COX-2 may play an important role in pancreatic tumorigenesis and therefore be a promising chemotherapeutic target for the treatment of pancreatic cancer.
Assuntos
Adenocarcinoma/enzimologia , Regulação Neoplásica da Expressão Gênica , Genes ras , Isoenzimas/biossíntese , Proteínas de Neoplasias/biossíntese , Neoplasias Pancreáticas/enzimologia , Mutação Puntual , Prostaglandina-Endoperóxido Sintases/biossíntese , Adenocarcinoma/genética , Animais , Linhagem Celular Transformada , Códon/genética , Cricetinae , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Dinoprostona/biossíntese , Dinoprostona/genética , Indução Enzimática , Humanos , Indometacina/farmacologia , Isoenzimas/genética , Proteínas de Membrana , Mesocricetus , Proteínas de Neoplasias/genética , Nitrobenzenos/farmacologia , Pâncreas/enzimologia , Neoplasias Pancreáticas/genética , Prostaglandina-Endoperóxido Sintases/genética , Transdução de Sinais , Sulfonamidas/farmacologia , Sulindaco/farmacologiaRESUMO
Two cases of synovial sarcoma that arose in the upper digestive tract are reported. One case was a polypoid mass that arose at the gastroesophageal junction; the other was a large intramural mass that arose in the wall of the stomach. Both cases had a classic biphasic pattern. In the stomach tumor, the biphasic morphology was focal and there was an abrupt transition to poorly differentiated synovial sarcoma. The tumors had immunohistochemical features that were consistent with synovial sarcoma. Ultrastructural evaluation of the gastroesophageal tumor supported the diagnosis. The diagnostic X;18 translocation was demonstrated by fluorescence in situ hybridization on sections from paraffin-embedded tissue in 86% and 50% of interphase nuclei from the gastroesophageal and gastric tumor, respectively. The translocation was present in equal frequency in the epithelial and spindle cells in the biphasic areas and the poorly differentiated areas of the gastric tumor, indicating that the development of the more aggressive subclone was probably due to genetic mutations not encompassing the SYT-SSX gene fusion product. We are aware of only five reported cases of synovial sarcoma arising in the digestive tract, all in the proximal esophagus. These cases are the first reported arising in the gastroesophageal junction and stomach and the only cases of synovial sarcoma of the digestive tract in which the diagnostic translocation was demonstrated. Sarcomatoid carcinoma (carcinosarcoma) and gastrointestinal stromal tumor are the main differential diagnoses for synovial sarcoma in this site. Synovial sarcoma of the digestive tract may be underdiagnosed, and its recognition may have important clinical implications. Fluorescence in situ hybridization is helpful in making this distinction.
Assuntos
Cromossomos Humanos Par 18/genética , Neoplasias Esofágicas/genética , Sarcoma Sinovial/genética , Neoplasias Gástricas/genética , Translocação Genética , Cromossomo X/genética , DNA de Neoplasias/análise , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Sarcoma Sinovial/patologia , Sarcoma Sinovial/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
We report four cases of Leydig cell tumor of the testis with a microcystic pattern that mimicked yolk sac tumor. The patients ranged in age from 27 to 35 years and, except for one tumor that was discovered incidentally, presented with testicular masses. All tumors were intratesticular, and three were well circumscribed by a rim of fibrous tissue, whereas one showed minor, focal extension into the adjacent testis. The tumors typically had a vaguely lobular architecture subdivided by fibrous bands. Three of the cases had a complex microcystic appearance caused by individually vacuolated cells and coalescent cystic spaces; this pattern accounted for the majority of two tumors. Another case had focal collections of Leydig cells with prominent cytoplasmic vacuoles but lacked the coalescent spaces. The microcyst contents ranged from optically clear to eosinophilic or lightly basophilic, with the latter having the staining qualities of acid mucopolysaccharide. Three tumors had uniform, bland nuclei and low mitotic rates (<1 mitotic figure per 10 high power fields), but one had marked, random nuclear pleomorphism and an average mitotic rate of five mitotic figures per 10 high power fields. By immunohistochemistry, all were diffusely positive for vimentin; two of three were positive for inhibin, and one showed focal positivity for cytokeratin (CAM 5.2). All were negative for alpha-fetoprotein and placentalike alkaline phosphatase and, apart from having microcystic and solid areas, lacked other features typical of yolk sac tumor. Clinical follow-up ranged from 2 months to 2 years with no patient having recurrence or metastasis. The distinction of Leydig cell tumor from yolk sac tumor has important clinical implications because patients with the former usually receive only clinical follow-up, but the latter often requires chemotherapy.
Assuntos
Cistos/patologia , Tumor de Células de Leydig/patologia , Neoplasias Testiculares/patologia , Adulto , Diagnóstico Diferencial , Tumor do Seio Endodérmico/patologia , Humanos , MasculinoRESUMO
We report a case of recurrent extramammary Paget's disease of the vulva, which clinically, grossly, and microscopically mimicked an invasive lesion. A 76-year-old woman presented with recent onset of vaginal bleeding, a nodular vulvar lesion, and left inguinal lymphadenopathy. Following a vulvar biopsy and endometrial curettage, the patient underwent a total hysterectomy and bilateral salpingo-oophorectomy with lymph node dissection and a modified radical vulvectomy with left inguinal node dissection. Papillary serous adenocarcinoma was found involving the uterus and one right common iliac lymph node. Sections through the vulvar nodule revealed a marked intraepithelial proliferation, which resulted in a complex epidermal hyperplasia with deep invaginations. Tangential sections of rete pegs filled with Paget's cells and surrounded by papillary dermis displaced into the deep reticular dermis mimicked invasive nests of tumor cells. The loose fibrous tissue of the displaced papillary dermis resembled a desmoplastic reaction. No true stromal invasion was present, and none of the inguinal lymph nodes were involved by Paget's cells. The Paget's disease did not resemble the uterine carcinoma by histopathologic and immunohistochemical study. Recognition of the intraepithelial nature of Paget's disease has important clinical implications, inasmuch as stromal invasion can be associated with metastatic disease.
Assuntos
Doença de Paget Extramamária/patologia , Neoplasias Vulvares/patologia , Idoso , Feminino , Humanos , Metástase Linfática/patologia , Invasividade Neoplásica/patologiaRESUMO
Eight Neisseria gonorrhoeae isolates, negative by direct fluorescent antibody (DFA) but positive by a DNA probe, were characterized by pulsed field gel electrophoresis and compared to eight DFA-positive, probe-positive isolates. Results indicate that DFA-negative, probe-positive Neisseria gonorrhoeae isolates may be clonal.