Analysis of prognostic value of complete response by PET–CT and further stratification by clinical and biological markers in DLBCL patients

Positron emission tomography–computed tomography (PET–CT) is performed as the standard method for response assessment of diffuse large B cell lymphoma (DLBCL) patients. However, a substantial proportion of patients experience relapse even if they have achieved complete response (CR) defined by PET–CT. We validated the prognostic value of CR by PET–CT and applied the National Comprehensive Cancer Network-International Prognostic Index (NCCN–IPI) and cell of origin (COO) to patients with CR by PET–CT to evaluate their additional predictive ability for survival outcomes. We retrospectively analyzed DLBCL patients who were treated with R-CHOP or an R-CHOP-like regimen and who achieved CR by PET–CT or CT only. A total of 185 patients were analyzed: 114 patients achieved CR by PET–CT and 71 patients by CT only. Patients with CR by PET–CT had significantly better overall survival (OS) than those with CR by CT (5-year OS, 87.5 vs. 62.4%, P = 0.003). Patients with high risk according to the NCCN–IPI had a dismal outcome despite achieving CR by PET–CT (5-year OS, 61.8%). In contrast, low-, low-intermediate-, and high-intermediate-risk patients had excellent outcomes (5-year OS, 100, 89.7, and 93.5%, respectively). Among patients with CR by PET–CT, patients with germinal center B cell (GCB) DLBCL (n = 40) had significantly better survival than those with non-GCB DLBCL (n = 57) (5-year OS, 96.9 vs. 75.5%, P = 0.039). We demonstrated that CR by PET–CT was a better predictor of survival outcomes than CR by CT only. The NCCN–IPI and COO subtypes could identify a subpopulation of poor-risk patients among those who achieved CR by PET–CT.     

Superficial basaloid squamous carcinoma of the esophagus. A clinicopathological and immunohistochemical study of 12 cases

Basaloid squamous carcinoma (BSC) is a rare variant of squamous cell carcinoma (SCC). In this study, clinicopathological and immunohistochemical characteristics of 12 superficial esophageal BSCs were examined and compared with those of typical superficial SCCs. Eight cases were classified into an elevated type, and the other four into a depressed type. High-grade intraepithelial neoplasia was not observed around the invasive lesions in five cases, and only BSC components were apparent. High-grade intraepithelial neoplasia was demonstrated in seven cases, five of which had both BSC and SCC components in the invasive lesion. A cribriform growth pattern, comedo-type necrosis, and hyaline deposits were conspicuous histological findings. CK14 was positively stained in 90% of the series, but the proportion of positive cells was small in most cases. Type IV collagen was increased or well preserved in the basement membrane in 70% of cases, but heparan sulfate was decreased in the majority. In comparison with SCCs, lymphatic permeation was observed less frequently. However, regarding the frequencies of venous permeation, nodal metastasis, p53 protein expression, and Ki-67 labeling index, no significant differences were noted. Thus, esophageal BSCs demonstrate the pathological features characteristic of an early stage, but pathological parameters related to biological behavior do not significantly vary from those typical of SCCs.     

Clinicopathological features of sporadic MSI colorectal cancer and Lynch syndrome: a single-center retrospective cohort study

International Journal of Clinical Oncology - The clinical and pathological features of sporadic microsatellite instability-high (MSI) colorectal cancer (CRC) are still unclear. The present study...     

Unusual type of left paraduodenal hernia caused by a separated peritoneal membrane

Internal hernias are an uncommon cause of intestinal obstruction, with left paraduodenal hernia being the most frequent of these. Computed tomography (CT) with contrast media is advantageous for the clinical workup of suspected paraduodenal hernias. Here, we report a case of an unusual paraduodenal sac formed by a peritoneal membrane between the transverse and the descending colon, which entrapped the proximal jejunum, causing intestinal obstruction. Preoperative CT demonstrated a cluster of jejunal loops between the stomach and pancreas, and showed that the inferior mesenteric vein was laterally displaced. Received: January 15, 2001 / Accepted: May 11, 2001 Reprint requests to: T. Nishida     

A novel case with germline p53 gene mutation having concurrent multiple primary colon tumours

During a search for causative genes in patients with concurrent multiple primary colon tumours, we found a novel case with a germline mutation of the p53 gene, from GCC (Ala) to GTC (Val) at codon 189. Of the six primary colon tumours that this patient had, one large advanced carcinoma exhibited a somatic p53 mutation and a somatic APC mutation, in addition to the germline p53 mutation. Two early carcinomas and three adenomas had somatic APC mutations but no somatic p53 mutation or loss of the p53 allele. K-ras-2 mutations were detected in an advanced carcinoma and an early carcinoma. The present results suggest that a patient with a certain type of germline p53 mutation is predisposed to concurrent multiple colon tumours. It is also suggested that in such a patient, a somatic APC mutation is involved in tumour formation and that an additional somatic p53 mutation contributes to tumour progression.     

Angiofibroma of soft tissue with fibrohistiocytic features and intratumor genetic heterogeneity of NCOA2 gene rearrangement revealed by chromogenic in situ hybridization: A case report

Angiofibroma of soft tissue is a recently described soft tissue tumor that is characterized by fibroblastic spindle tumor cells with arborizing capillary proliferation. Cytogenetically, it harbors a specific fusion gene involving the nuclear receptor coactivator 2 (NCOA2) gene. We report here additional new pathological and cytogenetic features. A soft tissue tumor in the left thigh of 73‐year‐old female was investigated. Microscopically, histiocytoid tumor cells were scattered in an edematous background with branching capillary proliferation. Immunohistochemically, we identified that the tumor cells were positive for histiocytic markers such as CD68 and CD163. Rearrangement of the NCOA2 gene was detected successfully by chromogenic in situ hybridization; however, abnormal signal patterns were observed in only a small subset of tumor cells. Unlike typical tumors with bland spindle cells, the present tumor needs to be distinguished from myxoid, dendritic and clear cell tumors. This case may suggest that angiofibroma of soft tissue is not in the center of the fibroblastic/myofibroblastic tumor group, but rather shows a fibrohistiocytic nature. We also found intratumor genetic heterogeneity, which is uncommon for a translocation‐associated tumor. Therefore, careful evaluation is required to detect the gene rearrangement in this tumor entity.     

Higher frequency of Smad4 gene mutation in human colorectal cancer with distant metastasis.

We have previously detected an increased frequency of loss of heterozygosity (LOH) on chromosome 18q during progression of colorectal carcinomas. To clarify the target of 18qLOH, mutation of Smad4 and Smad2 genes was analysed in 176 colorectal tumors with different stages, including liver metastasis, from 111 sporadic, 52 familial adenomatous polyposis (FAP) and nine hereditary nonpolyposis colorectal cancer (HNPCC) patients. Mutation of other Smad gene families in the TGF-beta signaling pathway was also examined. Twenty-one Smad4 mutations and one Smad2 mutation were detected, whereas mutation of Smad3, 6 and 7 genes was not detected. Smad4 mutations included seven frameshift, one inframe deletion, four nonsense and nine missense mutations, 95% of which resulted in alteration of Smad4 protein regions included in homo-oligomer and hetero-oligomer formation. Frequencies of tumors with Smad4 mutation were 0/40 (0%) in adenoma, 4/39 (10%) in intramucosal carcinoma, 3/44 (7%) in primary invasive carcinoma without distant metastasis, 6/17 (35%) in primary invasive carcinoma with distant metastasis, and 11/36 (31%) in distant metastasis (metastatic/non-metastatic: P=0.006 approximately 0.01). Loss of the other allele was observed in 19 of 20 (95%) invasive and metastasized carcinomas with Smad4 mutations. In four cases both primary and metastasized carcinomas in the same patients showed the same mutations. The present results suggest that Smad4 gene is one of true targets of 18qLOH, and that its inactivation is involved in advanced stages, such as distant metastasis, in human colorectal carcinogenesis.     

Beta‐2 microglobulin as a significant prognostic factor and a new risk model for patients with diffuse large B‐cell lymphoma

Previous reports have evaluated the prognostic value of serum beta‐2 microglobulin (B2MG) level in patients with non‐Hodgkin lymphoma. However, its role in predicting clinical outcome of patients with diffuse large B‐cell lymphoma (DLBCL) in the rituximab era has not been extensively investigated. Here, we evaluated the prognostic value of B2MG and proposed a new prognostic model including B2MG for patients with DLBCL. A total of 274 patients with newly diagnosed de novo DLBCL were retrospectively analyzed. We defined the best cutoff value as 3.2 mg/L by using a receiver operating characteristic curve. Patients with a B2MG level ≥3.2 mg/L had significantly lower overall survival (OS) and progression‐free survival than those with a B2MG level <3.2 mg/L (3‐year OS, 50.9% vs. 89.4%, p < 0.001; 3‐year progression‐free survival, 45.3% vs. 79.7%, p < 0.001). Multivariate analysis showed that B2MG, age, performance status, and Ann Arbor stage were independent prognostic factors for OS. We developed a new prognostic model consisting of these four significant factors. We stratified patients into four‐risk groups: low (L, 0 factor), low‐intermediate (LI, 1–2 factors), high‐intermediate (HI, 3 factors), high (H, 4 factors). This new prognostic model showed better risk discrimination compared with the National Comprehensive Cancer Network‐International Prognostic Index (5‐year OS: 100% and 23.4% vs. 100% and 27.1%, in L and H risk groups, respectively). Our study suggested that B2MG level is a significant prognostic factor in patients with DLBCL. A new prognostic index composed of age, performance status, stage, and B2MG could stratify the outcomes of patients with DLBCL effectively and appears to be a valuable risk model for these patients. Copyright © 2016 John Wiley & Sons, Ltd.     

Choroidal metastasis in a patient with small cell lung cancer discovered during treatment with chemotherapy

A 56-year-old male patient complaining of productive cough, hoarseness, and fatigue was found to have extensive disease of small cell lung cancer (ED-SCLC), with staging of cT4N3M1(PUL). He was treated with chemotherapy. While undergoing treatment with chemotherapy, he complained of a right visual disturbance, and choroidal metastasis was diagnosed. Because the primary site responded well to chemotherapy alone and the visual disturbance did not worsen, the patient refused radiotherapy to the choroidal metastasis. Two months after the first diagnosis of the choroidal metastasis, while he was receiving the first treatment regimen for SCLC, the visual disturbance suddenly worsened; emergent radiotherapy was started, with a total dose of 40 Gy, given as 2.0 Gy/fraction per day. The visual disturbance never improved, and the patient lost 80% of his right visual field. Within 6 months of diagnosis, the patient became blind in his right eye. The patient died of septic shock related to treatment received during his third chemotherapy regimen. Choroidal metastasis is very rare with extraocular malignant tumors, though it is common with intraocular malignant tumors. Choroidal metastasis secondary to SCLC has a poor prognosis, but in order to maintain quality of life during the patients’ remaining lifespan, aggressive treatment would appear appropriate for these patients, because SCLC is a chemo-sensitive cancer.