Primary Squamous Cell Carcinoma of the Upper Genital Tract: Utility of p16(INK4a) Expression and HPV DNA Status in its Differential Diagnosis from Extended Cervical Squamous Cell Carcinoma.

BACKGROUND: Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site. METHODS: We compared histologic findings, p16(INK4a) expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract. RESULTS: All five SCCs of cervical origin showed strong expression of p16(INK4a), whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA. CONCLUSIONS: Although a thorough histological examination is important, immunonegativity for p16(INK4a) and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract.

Clinical significance of signet-ring cells in colorectal mucinous adenocarcinoma.

Mucin occasionally accumulates intracellularly in colorectal mucinous adenocarcinomas, resulting in signet-ring cell morphology. In the current practice of pathology, there is no definitive rule on how to report a minor component of signet-ring cells in colorectal mucinous adenocarcinomas. We hypothesized that the absence of signet-ring cell component might have a favorable effect on survival of mucinous adenocarcinoma patients. To assess the biological characteristics of colorectal mucinous adenocarcinoma, we analyzed its clinicopathological features, microsatellite instability status, and survival outcomes and compared them with those of colorectal signet-ring cell carcinoma. A total of 266 consecutive colorectal mucinous adenocarcinoma patients and 65 signet-ring cell carcinoma patients were included. Mucinous adenocarcinomas, by comparison with signet-ring cell carcinomas, were characterized by development at an older age, less frequent vascular invasion and lymph node metastasis, and lower TNM stage at presentation. A total of 21 (22%) of 95 mucinous adenocarcinomas and 12 (19%) of 63 signet-ring cell carcinomas were high-frequency microsatellite instability. Patients with mucinous adenocarcinoma had significantly better survival than those with signet-ring cell carcinoma (P<0.0001) or than those with signet-ring cell carcinoma showing >50% extracellular mucin by volume (P<0.0001). In univariate analysis, absence of signet-ring cell component (P=0.0197), absence of vascular invasion, decreased invasion depth, no lymph node metastasis, and lower TNM stage had a favorable effect on survival of mucinous adenocarcinoma patients. Absence of vascular invasion, no lymph node metastasis, and lower TNM stage had a favorable effect on survival of signet-ring cell carcinoma patients. Multivariate analysis showed that higher TNM stage and T stage 4 were independent predictors of poor outcome in patients with mucinous adenocarcinoma. Our observations strongly suggest that pathologists should report the percentage of signet-ring cell component in colorectal mucinous adenocarcinomas and mucinous adenocarcinoma has different biologic behavior compared with signet-ring cell carcinoma.

Prognostic significance of p53 overexpression after hepatic resection of hepatocellular carcinoma.

BACKGROUND/AIMS: p53 mutation is the most common genetic abnormality in human cancers. However, although it has been reported that p53 overexpression in hepatocellular carcinoma (HCC) is associated with the aggressive behavior of tumor, the prognostic significance of p53 overexpression in HCC remains controversial. The aims of the present study were to examine the correlations between p53 overexpression and the clinicopathologic parameters of HCCs, and to determine the prognostic significance of p53 overexpression in HCC. METHODS: Immunohistochemical analysis of p53 overexpression was performed in 105 consecutive cases of HCC who underwent curative hepatic resection. Survival curves were calculated using the Kaplan-Meier method and multivariate analysis of outcome predictors for HCCs was assessed by logistic regression analysis. RESULTS: p53 overexpression was observed in 20 of 105 HCCs (19.0%). Multivariate analysis identified significant correlations between p53 overexpression and microvascular invasion (p=0.027), liver cirrhosis (p=0.035), 1-year survival rate (p=0.016), multiple tumors (p=0.014), and the presence of tumor capsule (p=0.010). The 2-year survival rate was poorer in patients without tumor capsule (p=0.043). CONCLUSIONS: Our results show a positive association between p53 overexpression and microvascular invasion in HCC, and indicate that p53 overexpression is a poor prognostic factor of survival, especially within 1 year after liver resection in HCC patients.

Bone marrow is involved in less than 10% of patients with nasal-type NK/T cell lymphoma at initial diagnosis.

To evaluate the frequency of bone marrow involvement by nasal-type NK/T cell lymphoma, we retrospectively studied biopsy specimens from 40 patients by EBV in situ hybridization (ISH). Three patients had marrow involvement at initial diagnosis (7.5%). In one patient (1/40, 2.5%), the disease in bone marrow was recognized by routine morphological assessment, while two other patients had minimal involvement of lymphoma cells which was recognized only by EBV in situ hybridization (2/40, 5%). Two patients had a disseminated disease at diagnosis and died 6 days and 214 days after diagnosis. One patient had diffuse colonic lesion and died 82 days later. In conclusion, marrow involvement in nasal NK/T cell lymphoma is infrequent at initial diagnosis, and EBV ISH is a useful technique for identifying the minor subgroup of patients which have easily overlooked neoplastic involvement.