Shinichiro Hiraiwa

Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV‐8‐negative multicentric Castleman disease

Multicentric Castleman disease (MCD) describes a heterogeneous group of disorders involving systemic inflammation, characteristic lymph node histopathology, and multi‐organ dysfunction because of pathologic hypercytokinemia. Whereas Human Herpes Virus‐8 (HHV‐8) drives the hypercytokinemia in a cohort of immunocompromised patients, the etiology of HHV‐8‐negative MCD is idiopathic (iMCD). Recently, a limited series of iMCD cases in Japan sharing a constellation of clinical features, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been described as TAFRO syndrome. Herein, we report clinicopathological findings on 25 patients (14 males and 11 females; 23 Japanese‐born and two US‐born), the largest TAFRO syndrome case series, including the first report of cases from the USA. The median age of onset was 50 years old (range: 23–72). The frequency of each feature was as follows: thrombocytopenia (21/25), anasarca (24/25), fever (21/25), organomegaly (25/25), and reticulin fibrosis (13/16). These patients frequently demonstrated abdominal pain, elevated serum alkaline phosphatase levels, and acute kidney failure. Surprisingly, none of the cases demonstrated marked hypergammoglobulinemia, which is frequently reported in iMCD. Lymph node biopsies revealed atrophic germinal centers with enlarged nuclei of endothelial cells and proliferation of endothelial venules in interfollicular zone. 23 of 25 cases were treated initially with corticosteroids; 12 patients responded poorly and required further therapy. Three patients died during the observation period (median: 9 months) because of disease progression or infections. TAFRO syndrome is a unique subtype of iMCD that demonstrates characteristic clinicopathological findings. Further study to clarify prognosis, pathophysiology, and appropriate treatment is needed. Am. J. Hematol. 91:220–226, 2016.

Manually controlled targeted prostate biopsy with real‐time fusion imaging of multiparametric magnetic resonance imaging and transrectal ultrasound: An early experience

To report our early experience with manually controlled targeted biopsy with real‐time multiparametric magnetic resonance imaging and transrectal ultrasound fusion images for the diagnosis of prostate cancer.

Clinicopathological characteristics and genomic profile of primary sinonasal tract diffuse large B‐cell lymphoma (DLBCL) reveals gain at 1q31 and RGS1 encoding protein; high RGS1 immunohistochemical expression associates with poor overall survival in DLBCL NOS

We aimed to define the clinicopathological characteristics of 29 primary sinonasal diffuse large B cell lymphoma (DLBCLsn) in a series of 240 cases of DLBCL not otherwise specified [DLBCLall (NOS)], including DLBCLsn training set (n = 11) and validation set (n = 18), and DLBCLnon‐sn (n = 211).

Hepatic adrenal rest tumor: Diagnostic pitfall and proposed algorithms to prevent misdiagnosis as lipid-rich hepatocellular carcinoma.

We present a case of adrenal rest tumor of the liver in which differential diagnosis from lipid rich‐hepatocellular carcinoma (HCC) was challenging. The patient was a 50‐year‐old woman in whom a 3‐cm tumorous mass was discovered in segment 7 of the liver during computed tomography evaluation of a uterine leiomyoma. The preoperative diagnosis was HCC, and subsegmental liver resection was performed. The tumor appeared as a well‐demarcated golden yellow nodule consisting of clear or partially eosinophilic cells arranged in a trabecular pattern. The initial impression of this lesion was that of clear cell type or lipid‐rich type HCC because it stained positive for Hep Par1, but negative for arginase‐1 and positive for CD56 which is one of the neuroendocrine markers. The lesion also stained positive for SF‐1 and 3β‐HSD, both of which are markers of adrenocortical tissue. The final diagnosis was hepatic adrenal rest tumor. Hepatic adrenal rest tumor should be considered in the differential diagnosis of segment 7 tumor. A diagnostic algorithm that includes immunohistochemical staining for CD56 and arginase‐1 is to rule out the possibility of lipid‐rich HCC.

Accuracy of real-time magnetic resonance imaging-transrectal ultrasound fusion image-guided transperineal target biopsy with needle tracking with a mechanical position-encoded stepper in detecting significant prostate cancer in biopsy-naïve men

To evaluate the accuracy of real‐time elastic fusion image‐guided transperineal prostate biopsy with needle tracking involving a mechanical position‐encoded stepper in detecting clinically significant prostate cancer for biopsy‐naïve men.

Clinicopathological and genomic analysis of double-hit follicular lymphoma: comparison with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements

Most high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are aggressive B-cell lymphomas. Occasional double-hit follicular lymphomas have been described but the clinicopathological features of these tumors are not well known. To clarify the characteristics of double-hit follicular lymphomas, we analyzed 10 cases of double-hit follicular lymphomas and 15 cases of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements for clinicopathological and genome-wide copy-number alterations and copy-neutral loss-of-heterozygosity profiles. For double-hit follicular lymphomas, the median age was 67.5 years (range: 48–82 years). The female/male ratio was 2.3. Eight patients presented with advanced clinical stage. The median follow-up time was 20 months (range: 1–132 months). At the end of the follow-up, 8 patients were alive, 2 patients were dead including 1 patient with diffuse large B-cell lymphoma transformation. Rearrangements of MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6 were seen in 8, 1, and 1 cases, respectively. The partner of MYC was IGH in 6 cases. There were no cases of histological grade 1, 4 cases of grade 2, 5 cases of grade 3a, and 1 case of grade 3b. Two cases of grade 3a exhibited immunoblast-like morphology. Immunohistochemistry demonstrated 9 cases with ≥50% MYC-positive cells. There was significant difference in MYC intensity (P=0.00004) and MIB-1 positivity (P=0.001) between double-hit follicular lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. The genome profile of double-hit follicular lymphomas was comparable with conventional follicular lymphomas (GSE67385, n=198) with characteristic gains of 2p25.3-p11.1, 7p22.3-q36.3, 12q11-q24.33, and loss of 18q21.32-q23 (P<0.05). In comparison with high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements, double-hit follicular lymphomas had fewer copy-number alterations and minimal common region of gain at 2p16.1 (70%), locus also significant against conventional follicular lymphomas (P=0.0001). In summary, double-hit follicular lymphomas tended to be high-grade histology, high MYC protein expression, high MYC/IGH fusion, and minimal common region of gain at 2p16.1. Double-hit follicular lymphomas seemed to be a different disease from high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements and have an indolent clinical behavior similar to follicular lymphomas without MYC rearrangement.

Novel application of three-dimensional shear wave elastography in the detection of clinically significant prostate cancer

The present study evaluated three-dimensional shear wave elastography (3D SWE) in the detection of clinically significant prostate cancer. Clinically significant prostate cancer was defined by a minimum of one biopsy core with a Gleason score of 3+4 or 6 with a maximum cancer core length >4 mm. Patients with serum prostate-specific antigen levels of 4.0-20.0 ng/ml who were suspected of having prostate cancer from multi-parametric magnetic resonance imaging (mpMRI) were prospectively recruited. The 3D SWE was performed pre-biopsy, after which patients underwent MRI-transrectal ultrasound image-guided targeted biopsies for cancer-suspicious lesions and 12-core systematic biopsies. The pathological biopsy results were compared with the mpMRI and 3D SWE images. A total of 12 patients who were suspected of having significant cancer on mpMRI were included. The median pre-biopsy PSA value was 5.65 ng/ml. Of the 12 patients, 10 patients were diagnosed as having prostate cancer. In the targeted biopsy lesions, there was a significant difference in Youngs modulus between the cancer-detected area (median 64.1 kPa, n=20) and undetected area (median 30.8 kPa, n=8; P<0.0001). On evaluation of receiver operating characteristics, a cut-off value of the Youngs modulus of 41.0 kPa was used for the detection of clinically significant cancer, with which the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cancer detection were 58, 97, 86 and 87%, respectively. When combining this cut-off tissue elasticity value with Prostate Imaging Reporting and Data System (PI-RADS) scores, the sensitivity, specificity, positive predictive value and negative predictive value of cancer detection were improved to 70, 98, 91 and 92%, respectively. In the cancer-detected lesions, a significant correlation was identified between the tissue elasticity value of the lesions and Gleason score (r=0.898, P<0.0001). In conclusion, PI-RADS combined with measurement of Youngs modulus by 3D SWE may improve the diagnosis of clinically significant prostate cancer.

IgG4-related Disease with Bone Marrow Involvement

A 61-year-old Japanese woman with anemia, submandibular gland swelling, and enlarged lymph nodes was diagnosed with IgG4-related disease (IgG4-RD) by lymph node biopsy. Bone marrow involvement of IgG4-RD was detected by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and immunohistochemically proven by bone marrow biopsy in this patient. Anemia progressed gradually, and prednisolone treatment was initiated. Anemia and submandibular gland swelling improved soon after prednisolone treatment was initiated. We report a rare case of IgG4-RD involving the bone marrow. FDG-PET/CT and bone marrow biopsy were useful for diagnosis in this case.

Three cases of spontaneous splenic rupture in malignant lymphoma

Spontaneous splenic rupture is a rare but often life-threatening condition. However, there is no consensus on appropriate management for this condition, due to its rarity. Here, we report three cases of malignant lymphoma with spontaneous splenic rupture. In each case, progression of splenic bleeding was rapid and complicated by malignant lymphoma. Spontaneous splenic rupture complicated by malignant lymphoma may cause exacerbation of anemia and hypovolemic shock. When splenic rupture is indicated by abdominal pain, tachycardia, or hypotension in a patient with splenomegaly, abdominal examination should be performed immediately, and emergency transcatheter arterial embolization and/or splenectomy should be considered.

Vessel Morphologies of the Brain in Cytological Squash Preparations Are Useful for Intraoperative Diagnosis of High-Grade Astrocytomas

Objective: The aim of this study was to determine whether intraoperative cytological evaluation of squash preparations is of benefit for differentiating high-grade from low-grade astrocytomas. Methods: Squash preparations of 42 astrocytomas were classified histologically according to the World Health Organization (WHO) 2007 classification system as grade II (n = 12), grade III (n = 11), and grade IV (n = 19) and were divided into 2 groups, namely a low-grade group (grade II) and a high-grade group (grades III and IV). The focus was on morphological cell and vessel characteristics, namely nuclear atypia, chromatin pattern, nuclear enlargement, variation in nuclear size, the presence of nucleoli, mitosis, tumor necrosis, cell density, multibranched vessels, and vascular dilatation, and these characteristics were compared between the low- and high-grade groups. Results: Nuclear atypia, the presence of coarse chromatin, variations in nuclear size, and cell density ≥200 per high-power field were significantly more prevalent in high- than in low-grade astrocytomas (p = 0.0407, p < 0.01, p < 0.01, and p < 0.01, respectively). Vessels with > 3 branches and a mean vessel diameter ≥20 μm were more prevalent in high- than in low-grade astrocytomas (p < 0.01). Conclusion: Squash preparation cytology provides added benefit for the intraoperative identification of high-grade astrocytoma.