Fumi Kawakami

Validation of the IASLC/ATS/ERS Lung Adenocarcinoma Classification for Prognosis and Association with EGFR and KRAS Gene Mutations: Analysis of 440 Japanese Patients

Introduction: This study aimed to validate the utility of the new histological classification proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) for identifying the prognostic subtypes of adenocarcinomas in Japanese patients; correlations between the classification and the presence of EGFR or KRAS mutation status were also investigated. Methods: We retrospectively reviewed 440 patients with lung adenocarcinoma, who underwent resection. The tumors were classified according to the IASLC/ATS/ERS classification. EGFR and KRAS mutations were detected using the established methods. Results: Five-year disease-free survival rates were: 100% for adenocarcinoma in situ (n = 20) and minimally invasive adenocarcinoma (n = 33), 93.8% for lepidic-predominant adenocarcinoma (n = 36), 88.8% for invasive mucinous adenocarcinoma (n = 10), 66.7% for papillary-predominant adenocarcinoma (n = 179), 69.7% for acinar-predominant adenocarcinoma (n = 61), 43.3% for solid-predominant adencoarcinoma (n = 78), and 0% for micropapillary-predominant adenocarcinoma (n = 19). Multivariate analysis revealed that the new classification was an independent predictor of disease-free survival. EGFR and KRAS mutations were detected in 90 cases (53.9%) and 21 cases (13.3%), respectively; EGFR mutations were significantly associated with adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic- and papillary-predominant adenocarcinoma, and KRAS mutations adenocarcinomas with mucinous tumor subtypes. Conclusions: We found that the IASLC/ATS/ERS classification identified prognostic histologic subtypes of lung adenocarcinomas among Japanese patients. Histologic subtyping and molecular testing for EGFR and KRAS mutations can help predict patient prognosis and select those who require adjuvant chemotherapy.

Ultra‐high b‐value diffusion‐weighted MRI for the detection of prostate cancer with 3‐T MRI

To determine, with histopathological findings of radical prostatectomy as reference, whether diffusion‐weighted imaging (DWI) using b = 2000 s/mm2 for 3‐T magnetic resonance imaging (MRI) is superior to the use of b = 1000 s/mm2 for prostate cancer detection.

Do apparent diffusion coefficient (ADC) values obtained using high b-values with a 3-T MRI correlate better than a transrectal ultrasound (TRUS)-guided biopsy with true Gleason scores obtained from radical prostatectomy specimens for patients with prostate cancer?

OBJECTIVE To investigate the usefulness of apparent diffusion coefficient (ADC) values in predicting true Gleason scores from radical prostatectomy specimen (tGS), compared with systematic transrectal ultrasound (TRUS)-guided biopsy GS (bGS). MATERIALS AND METHODS One hundred and five patients with biopsy-proven prostate cancer underwent preoperative DWI (b-values of 0, 1000, and 2000s/mm(2)) of 3-T MRI. The mean and minimum ADCs of visible tumors were calculated for either of a pair of b-values: 0 and 1000s/mm(2) (ADC1000), or 0 and 2000s/mm(2) (ADC2000), and relationships between the four ADC parameters and tGS evaluated for the peripheral zone (PZ) and transition zone (TZ). For multiple tumors, the dominant tumors GS and ADCs were estimated for cancer aggressiveness assessment by computing ROC curves. RESULTS Significant negative correlations were observed between tGS and mean ADC1000, mean ADC2000, minimum ADC1000, and minimum ADC2000 (r=-0.41, -0.39, -0.39, and -0.37, respectively) of 100 visible PZ tumors and 66 visible TZ tumors (r=-0.40, -0.42, -0.29, and -0.21, respectively). For distinguishing high-grade from low/intermediate-grade PZ lesions, the areas under the curve (AUCs) of mean ADC1000 (0.751), mean ADC2000 (0.710), minimum ADC1000 (0.768), and minimum ADC2000 (0.752) were similar to that of the highest bGS (0.708) (p=0.61, p=0.98, p=0.47, and p=0.60, respectively). For distinguishing high-grade from low/intermediate-grade TZ lesions, AUCs of mean ADC1000 (0.779), and mean ADC2000 (0.811) were similar to that of the highest bGS (0.805) (p=0.83 and p=0.97). CONCLUSION Tumor ADCs obtained with high b-values could predict prostate cancer aggressiveness as effectively as systematic TRUS-guided biopsy.

Triexponential function analysis of diffusion‐weighted MRI for diagnosing prostate cancer

To evaluate more detailed information noninvasively through on diffusion and perfusion in prostate cancer (PCa) using triexponential analysis of diffusion‐weighted imaging (DWI).

Multiple solid pancreatic hamartomas: A case report and review of the literature

Non-neoplastic tumor-like lesions in the pancreas are uncommon. Here, we present a case of multiple solid pancreatic hamartomas in a 78-year-old Japanese woman. Her computed tomography revealed a pancreatic mass, measuring 1.8 cm in maximum diameter. However, no symptoms were found. She was not an alcoholic and had no history of pancreatitis. The patient underwent a pancreatoduodenectomy, and three well-demarcated solid nodules measuring 1.7 cm, 0.4 cm, and 0.3 cm in diameter were found in the pancreatic head. Microscopically, the lesions were composed of non-neoplastic, disarranged acinar cells and ducts embedded in a sclerotic stroma with elongated spindle cells that lacked discrete islets. The stromal spindle cells were immunoreactive for CD34 and CD117. The histological diagnosis was multiple solid hamartomas of the pancreas. There has been no recurrence 30 mo after surgery. So far, 18 cases of pancreatic hamartoma have been reported in the English literature, including our case. Six out of these 18 cases seemed to fit the criteria of solid pancreatic hamartoma. Although the number of cases was limited, solid pancreatic hamartomas seem to be benign tumor-like lesions, which are found incidentally in healthy middle-aged adults, but occasionally involve the whole pancreas, resulting in a poor prognosis. Solid pancreatic hamartoma was sometimes associated with minor pancreatic abnormality, and multiple small lesions other than the main tumors were detected in a small number of cases. From these findings, one may speculate that solid pancreatic hamartoma could be the result of a malformation during the development of the pancreas.

Distinctive histopathologic findings of pancreatic hamartomas suggesting their "hamartomatous" nature: a study of 9 cases.

Pancreatic hamartoma is a rare tumor, and its characteristic histopathologic features have not yet been fully evaluated. In this study, we collected 9 cases of pancreatic hamartoma to elucidate distinctive histopathologic features that can serve to establish this tumor as a clear disease entity and thus formulate useful histopathologic criteria for this tumor. The cases comprised 4 men and 5 women with a mean age of 62.7 years. The average tumor diameter was 3.3 cm. All patients underwent surgical treatment, and none showed any recurrence postoperatively. Macroscopically, pancreatic hamartomas were well-demarcated tumors with a solid or solid and cystic appearance. Microscopically, these tumors comprised mature acini and small-sized to medium-sized ducts showing a distorted architecture with various amounts of fibrous stroma. Strikingly, the tumors consistently lacked concentric elastic fibers in their duct walls, peripheral nerves, and well-formed islets of Langerhans, all of which exist in both the normal and atrophic pancreas. Immunohistochemically, scattered chromogranin A-positive neuroendocrine cells were observed in the acinar and ductal components. Ductal components were positive for S-100 protein. Spindle-shaped stromal cells expressed CD34 and/or c-kit. These histopathologic features were distinct from those of 5 cases of pancreatic ductal adenocarcinoma, 3 cases of type 1 autoimmune pancreatitis (lymphoplasmacytic sclerosing pancreatitis), 3 cases of alcoholic chronic pancreatitis, and 5 cases of normal pancreas. In conclusion, pancreatic hamartomas share some distinctive histopathologic features and clinical outcomes (neither recurrence nor metastasis) that allow them to be interpreted as malformative lesions. The term “hamartoma” is appropriate for these unique lesions.

Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dube syndrome

In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors.

Immunohistochemical characterization of renal tumors in patients with Birt-Hogg-Dubé syndrome.

Birt‐Hogg‐Dubé syndrome (BHD) is an autosomal dominant disorder associated with a germline mutation of folliculin (FLCN). The affected families are at a high risk for developing multiple renal cell carcinomas (RCC). Little is known about the immunostaining patterns of mutant FLCN‐associated RCCs. We investigated 32 RCCs obtained from 17 BHD patients. The studied tumors included chromophobe RCCs (n = 15), hybrid oncocytic/chromophobe tumors (HOCT) (n = 14) and clear cell RCCs (n = 3). Almost all chromophobe RCCs and HOCTs revealed positive staining for S100A1, Ksp‐cadherin and CD82. They stained either focally or diffusely for CK7, and were negative for CA‐IX. All clear cell RCCs were positively stained for CA‐IX and negative for CK7. These data confirmed that mutant FLCN‐associated oncocytic and clear cell RCCs exhibited generally similar immunostaining patterns compared to their sporadic counterparts. Frequent positive staining for S100A1, Ksp‐cadherin and CD82 in chromophobe RCCs and HOCTs indicated that these two types were relatively similar rather than distinctively different in their patterns of immunoreactivity. Characteristic peri‐nuclear halos and polygonal cells with clear cytoplasm, which often misleads pathologists into the diagnosis of clear cell RCC, should be carefully examined using an immunohistochemical panel including CA‐IX, Ksp‐cadherin, CD82 and CK7.

Primary submucosal nodular plasmacytoma of the stomach: a poorly recognized variant of gastric lymphoma

AbstractGastric plasmacytoma (GP) is a rare variant of gastric lymphomas. In the exceptional event that a patient presents with GP, the lesion occupies the mucosal layer in the vast majority of cases. Here we report a case of nodular plasmacytoma confined to the submucosa with no evidence of Helicobacter pylori (Hp) infection. The patient was a 59-year old female presenting with no particular symptoms. The tumor was well-demarcated and consisted of a diffuse monomorphic proliferation of plasma cells with numerous lymphoid follicles scattered throughout the tumor. The mucosal surface was intact and not associated with any tumor nodules. The cells were diffusely positive for CD79a, Bob1, EMA and IgA and consistently negative for CD3, CD19, CD20, PAX5, CD56, IgM and IgG. Additionally, in situ hybridization demonstrated clonality in the form of λ light-chain restriction. This submucosal nodular proliferation pattern of plasmacytoma is poorly recognized and considered to be a novel variant of lymphoma.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3489998708673079

Large cell neuroendocrine carcinoma originating from the uterine endometrium: a report on magnetic resonance features of 2 cases with very rare and aggressive tumor.

Neuroendocrine carcinomas (NEC) of the female genital tract are aggressive and uncommon tumors, which usually involve the uterine cervix and ovary, and are seen very rarely in the endometrium. Only less than 10 cases of large cell NEC (LCNEC) of the endometrium have been reported in the literature and their radiological findings are not well described. We report here two cases of pathologically proven LCNEC of the uterine endometrium. In both cases, the uterine body was enlarged and the tumor occupied part of the uterine cavity. Endometrial mass exhibited heterogeneous high intensity on T2-weighted magnetic resonance (MR) images, and diffusion-weighted MR images revealed high intensity throughout the tumor, consistent with malignancy. LCNEC is a highly malignant neoplasm without particular findings in terms of diagnostic imaging and pathology, so its preoperative definitive diagnosis is very difficult. However, when laboratory test, pathologic diagnosis and MR imaging suggest a poorly differentiated uterine malignancy, positron emission tomography-computed tomography scan should be performed as a general assessment to help with diagnosis.