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Am J Surg Pathol ; 42(12): 1715-1722, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30212392


Signet ring cell carcinomas of the gastrointestinal (GI) tract are clinically aggressive neoplasms with frequent intra-abdominal metastases at initial presentation. Currently available immunohistochemistry (IHC) markers cannot distinguish signet ring cell carcinomas of the lower GI tract and upper GI tract, suggesting the need for more specific diagnostic markers. SATB2 is a novel, sensitive marker for colorectal carcinoma. We hypothesized that SATB2 IHC can reliably identify primary and metastatic signet ring cell carcinomas of lower GI tract origin. SATB2 and CDX2 IHC was performed on 159 primary (n=93) and metastatic (n=66) signet ring cell carcinomas of GI tract origin and 13 metastatic breast carcinomas with signet ring cell features. Positive SATB2 expression (SATB2) was identified in 82% (27/33) of appendiceal, 88% (43/49) of colorectal, 13% (7/54) of gastric, and 35% (8/23) of esophageal/esophagogastric junction signet ring cell carcinomas. Primary and metastatic signet ring cell carcinomas of lower GI tract origin were more frequently SATB2 than those from upper GI tract (70/82, 85% vs. 15/77, 19%, P<0.01). Compared with CDX2, SATB2 and dual-positive staining for SATB2 and CDX2 both had higher specificities for signet ring cell carcinomas from the lower GI tract (81% vs. 49% and 86% vs. 49%, respectively, P<0.01 for both). Two (15%) metastatic breast carcinoma were SATB2, but all 13 demonstrated negative CDX2 staining. In summary, our results show SATB2 is a relatively specific immunohistochemistry marker for both metastatic and primary signet ring cell carcinomas of lower GI tract origin.

Am J Surg Pathol ; 42(10): 1409-1417, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30001238


The special AT-rich sequence binding protein (SATB2) has been reported to be a specific immunohistochemical marker for colorectal carcinoma; however, correlation of SATB2 expression with molecular alterations commonly assessed in colorectal carcinoma has not been performed. We examined the immunohistochemical expression of SATB2 in 586 adenocarcinomas of the gastrointestinal (GI) tract and pancreas to assess its utility in diagnosis and analyze the clinicopathologic and molecular characteristics of colorectal carcinoma stratified by SATB2 expression. SATB2 and CDX2 expression were evaluated in 266 adenocarcinomas of lower GI tract origin (246 colorectal and 20 appendiceal mucinous), 208 adenocarcinomas of upper GI tract and small intestinal origin (74 esophagus/esophagogastric junction, 103 stomach, 20 duodenal, and 11 jejunoileal), and 112 pancreatic ductal adenocarcinomas. SATB2 expression was more frequently identified in adenocarcinomas of lower GI tract origin (222/266, 83%) compared with upper GI tract, small intestinal, or pancreatic origin (26/320, 8%) (P<0.001). Compared with CDX2 alone, dual positive expression for SATB2 and CDX2 (SATB2/CDX2) has a significantly higher specificity for adenocarcinoma of lower GI tract origin (94% vs. 57%, P<0.001). In colorectal carcinoma, loss of SATB2 expression was more frequently observed in DNA mismatch repair (MMR) protein deficient tumors (31%) compared with MMR protein proficient tumors (13%) (P<0.01). A BRAF V600E mutation was more frequently identified in colorectal carcinomas with loss of SATB2 expression compared with those with positive SATB2 expression (29% vs. 3%) (P<0.001). In summary, SATB2 expression is a relatively specific marker of lower GI tract origin; however, loss of SATB2 expression is more commonly seen in colorectal carcinoma with MMR protein deficiency and BRAF mutation.

Case Rep Pathol ; 2017: 3427343, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28840050


Medullary carcinoma has long been recognized as a subtype of colorectal cancer associated with microsatellite instability and Lynch syndrome. Gastric medullary carcinoma is a very rare neoplasm. We report a 67-year-old male who presented with a solitary gastric mass. Total gastrectomy revealed a well-demarcated, poorly differentiated carcinoma with an organoid growth pattern, pushing borders, and abundant peritumoral lymphocytic response. The prior cytology was cellular with immunohistochemical panel consistent with upper gastrointestinal/pancreaticobiliary origin. Overall, the histopathologic findings were consistent with gastric medullary carcinoma. A mismatch repair panel revealed a mismatch repair protein deficient tumor with loss of MLH1 and PMS2 expression. BRAF V600E immunostain (VE1) and BRAF molecular testing were negative, indicating a wild-type gene. Tumor sequencing of MLH1 demonstrated a wild-type gene, while our molecular panel identified TP53 c.817C>T (p.R273C) mutation. These findings were compatible with a sporadic tumor. Given that morphologically identical medullary tumors often occur in Lynch syndrome, it is possible that mismatch repair loss is an early event in sporadic tumors with p53 mutation being a late event. Despite having wild-type BRAF, this tumor is sporadic and unrelated to Lynch syndrome. This case report demonstrates that coordinate ancillary studies are needed to resolve sporadic versus hereditary rare tumors.

Int J Surg Pathol ; 25(8): 716-720, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28633553


Giant bullous emphysema with placental transmogrification is an extremely rare entity, with 30 previously reported cases. Of these reported cases, it is typically identified with varied clinical and radiological impressions, presents in young adulthood to elderly, is always unilateral, and usually involves just one lobe. Despite the unknown pathogenesis, this diagnosis carries an excellent prognosis and is curative with complete resection. The pulmonary placental transmogrification is histologically indistinguishable from placental origin. Although not necessary to utilize because of the male predominance and no reported association, immunohistochemical stains can be used to prove lung origin. We report an extremely rare case of 2-lobe involvement of giant bullous emphysema with placental transmogrification in a boy 14 years of age, who is the youngest diagnosed patient with this lung abnormality.

Pulmão/patologia , Enfisema Pulmonar/patologia , Adolescente , Humanos , Masculino
Urology ; 102: 7-16, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27769917


Urothelial carcinoma can exhibit a wide variety of histopathologic phenotypes or variant morphologies, classifications of which have recently been revised in the 2016 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs. Many of these variants not only present diagnostic challenges, but also have clinical implications that affect patient prognosis and treatment strategies. This review will discuss these variant morphologies and their relationship to current understanding of the underlying biology of urothelial carcinoma and molecular classification paradigms.

Carcinoma de Células de Transição/diagnóstico , Neoplasias Urológicas/diagnóstico , Carcinoma de Células de Transição/classificação , Carcinoma de Células de Transição/patologia , Humanos , Técnicas de Diagnóstico Molecular , Neoplasias Urológicas/classificação , Neoplasias Urológicas/patologia
JAMA Dermatol ; 150(11): 1160-6, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25055194


IMPORTANCE: This study highlights a simple bedside evaluation of itch and pain for suspicious skin lesions. OBJECTIVE: To examine the correlation of pain and itch with histologic features of skin cancers. DESIGN, SETTING, AND PARTICIPANTS: This large, prospective, clinicopathologic study enrolled patients who filled out questionnaires that assessed itch and pain intensity of their skin tumors at the time of excision. Study participants were from the patient population presenting to the Department of Dermatology surgical unit at Wake Forest University Baptist Medical Center from July 1, 2010, through March 31, 2011. Study participants included 268 patients, representing 339 histopathologically confirmed cutaneous neoplasms. The following skin cancer subtypes were represented in this analysis: 166 basal cell carcinomas, 146 squamous cell carcinomas, and 27 melanomas. MAIN OUTCOMES AND MEASURES: Itch and pain associated with skin cancer at the time of excision ranked on an 11-point (score range, 0-10) numerical visual analog scale and histopathologic analysis for each neoplasm (assessment of the amount and type of inflammation, ulceration, perineural invasion, and depth of invasion). RESULTS: The prevalence of itch and pain across all skin cancers was 36.9% and 28.2%, respectively. However, these symptoms were mostly absent in melanomas. Pain intensity was significantly associated with the degree of inflammation (mild or none vs moderate or marked; P < .001), presence of neutrophils in the inflammatory infiltrate (predominantly mononuclear vs mixed or neutrophilic; P = .003), presence of eosinophils (present vs absent; P = .007), ulceration (yes vs no; P = .003), perineural invasion (yes vs no; P < .001), depth of invasion (P = .001), and largest diameter length of skin lesion (P < .003). Itch intensity was significantly associated with the degree of inflammation (mild or none vs moderate or marked; P = .001) and the presence of eosinophils (present vs absent; P = .02). CONCLUSIONS AND RELEVANCE: These findings support the theory that itch emanates from the upper layers of the skin, whereas pain is associated with deeper processes. This study also reports that a simple bedside assessment for the presence and intensity of pain or itch is an easily implementable tool for physicians evaluating suspicious skin lesions.

Eosinófilos/metabolismo , Inflamação/etiologia , Dor/etiologia , Prurido/etiologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/patologia , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Inflamação/epidemiologia , Inflamação/patologia , Masculino , Melanoma/epidemiologia , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica , Dor/epidemiologia , Medição da Dor , Prevalência , Estudos Prospectivos , Prurido/epidemiologia , Neoplasias Cutâneas/cirurgia , Inquéritos e Questionários