Clinicopathologic analysis of malignant or premalignant cutaneous neoplasms in Japanese kidney transplant recipients.

It is well known that recipients of kidney transplants are at an increased risk of developing malignant or premalignant cutaneous neoplasms (MPCNs) after transplantation. However, the pathogenesis of MPCNs after kidney transplant has not been well-studied in Asian populations. This study aimed to describe the clinicopathologiccharacteristics of MPCNs in an Asian population. We retrospectively reviewed the medical records of 1956 patients who received kidney transplants at two hospitals in Japan, between 2003 and 2019. Among these patients, 24 developed 50 MPCN lesions, including 14 squamous cell carcinoma (SCC, 28%), 23 Bowen's disease (BD, 46%), 11 actinic keratosis (AK, 22%), and two basal cell carcinoma (BCC, 4%). No patient had malignant melanoma. The duration from transplantation to the diagnosis was significantly longer for SCC than for BD or AK (P=0.021, 0.036, respectively). Seven patients had multiple MPCNs in sun-exposed areas of skin. Among the 50 MPCNs, 40 (80%) were located in sun-exposed areas, and 10 (20%) were located in sun-protected areas. MPCNs in sun-exposed skin were frequently accompanied by dermal solar elastosis (90%, 36/40). We found high-risk human papillomavirus (HR-HPV) infections in two anogenital lesions (100%, 2/2). In contrast, HR-HPV infections were not detected in any extragenital lesions (0%, 0/30). Our results suggested that, among Japanese recipients of kidney transplant, MPCNs in sun-exposed skin areas may be associated with immunosuppression and ultraviolet exposure.

Calculating the Tumor Nuclei Content for Comprehensive Cancer Panel Testing.

Comprehensive genetic panel testing generally requires that the analyzed tissues have a percent tumor nuclei (%TN) content of 20% or more to achieve assay performance comparable to the validated specifications. Pathologists play a crucial role in ensuring that the optimal results are achieved by accurately assigning %TN content of the available specimens and selecting the best material to submit for sequencing. This study addresses the issues in evaluating %TN, such as intraobserver variability, and examines whether focused training and feedback can improve pathologist performance. Nine referring institution pathologists (all board-certified and working at the core institute and the alignment hospitals under the National Cancer Genome scheme) evaluated 18 tumors that had been subjected to comprehensive genetic panel testing with the FoundationOne CDx assay. The %TN estimates provided by referring institution pathologists were compared with two standards: %TN assigned by the tumor sequencing institution's pathologist (a board-certified pathologist at Foundation Medicine, Inc.) and the computational %TN estimated from the mutant allele frequencies after sequencing was completed. The pathologists generally overestimated %TN in the first pretraining round of the evaluation, and the differences in the averaged %TN from the tumor sequencing institution and computational standards were statistically significant. However, the posttraining second-round results became significantly concordant with the standards. This study suggests that %TN content is empirically overestimated but the evaluation skill can be improved by providing a training and feedback program.

[Intrasellar xanthogranuloma with abscess formation in a patient with Rathke's cleft cyst].

An 80-year-old woman diagnosed with granulomatosis with polyangiitis (GPA) complained of a sustained, non-pulsatile headache. Her brain MRI diffusion-weighted images revealed a high-signal-intensity, space-occupying lesion in the sellar region that was rim-enhanced on gadolinium-enhanced T1-weighted images. Pituitary involvement of GPA was initially suspected based on her condition; however, an abscess formation within an existing Rathke's cleft cyst was also considered according to a previous MRI finding that had been conducted for an unrelated purpose. A trans-sphenoidal resection of the lesion revealed an abscess with foam cells. These findings were consistent with a diagnosis of a xanthogranuloma with abscess formation in the Rathke's cleft cyst, and her headache was completely resolved without any immune therapy that is required for GPA. Thus, differential diagnosis of space-occupying lesions in the seller region should include xanthogranuloma with abscess formation, especially if a Rathke's cleft cyst is detected as an antecedent finding.

[Recent advances in prostate pathology].

Gleason score was revised in 2005 by International Society of Urological Pathology (ISUP). This revision has great impacts on prostate cancer diagnosis and treatment. However, some issues were not reached to consensus. In addition, some modifications are needed to adapt recent advanced prostate cancer therapies, especially for patients with active surveillance and very high risk prostate cancer. The authors review recently updated Gleason grading system by ISUP, which will fit to recent prostate cancer treatment. There are few prognostic factors to predict cancer specific survival and overall survival. The authors show the concept and diagnostic criteria of IDC-P. The authors also discuss clinical usefulness and problems of IDC-P in practice.

Alpha methylacyl-CoA racemase (AMACR) in prostate adenocarcinomas from Japanese patients: is AMACR a "race"-dependent marker?

BACKGROUND: Alpha methylacyl-CoA racemase (AMACR) is a useful diagnostic marker for prostate adenocarcinoma. However, its usefulness has not been fully validated in Japanese patients. The aim of this study was to evaluate the diagnostic utility of AMACR in prostate needle biopsy examination in Japanese patients. METHODS: A total of 119 prospective consecutive prostate needle biopsy specimens (680 cores) obtained from Japanese patients were examined. Sixty patients had adenocarcinoma (adenocarcinoma, 160 cores; benign, 204 cores), 14 patients had high-grade prostatic intraepithelial neoplasia (HGPIN; 19 cores), and 45 patients did not have any neoplastic lesions (297 cores). AMACR expression was scored semi-quantitatively as 0 (no expression), 1+ (partial and/or weak expression), or 2+ (strong, circumferential expression). The number of positively stained glands was counted. RESULTS: 2+ AMACR expression was observed in 70.1% of adenocarcinoma cases and in 52.6% of HGPIN cases. Of the adenocarcinoma cases showing 2+ AMACR expression, 34.8% demonstrated a heterogeneous expression pattern, with 1-75% of AMACR-positive glands. Three hundred eighty-five of the benign glands with an adenocarcinoma component showed 2+ AMACR expression (35 cases, 94 cores). 2+ AMACR expression was observed in 67 non-neoplastic benign glands (9 cases, 19 cores). CONCLUSIONS: The sensitivity and specificity of AMACR for the diagnosis of prostate adenocarcinoma and benign glands in Japanese patients are lower than those previously reported in Western countries. Pathologists should be cautious while interpreting AMACR expression pattern in Japanese patients.

Immunocytochemical analysis for differential diagnosis of thyroid lesions using liquid-based cytology.

Recently, liquid-based cytology (LBC) has been widely applied to various samples in diagnostic cytology and its usefulness has been reported. In this study, we investigated thyroid cytology that applied LBC and immunocytochemistry to achieve more objective diagnosis and greater diagnostic accuracy. This study included 125 cases (57 papillary carcinomas (PCs), 22 follicular tumors, 43 adenomatous goiters and 3 with Basedow's disease). After preparing the LBC slide, immunocytochemical staining was performed on each slide with six antibodies (HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (34JE12), galectin-3, CD15 and CA 19-9). All antibodies presented immunopositivity frequently in PCs, but only a few or some of them were positive in other cases. These antibodies were considered positive markers for PCs, and the most reliable marker was 34betaE12; its sensitivity, specificity and diagnostic accuracy were 82.5%, 100% and 92.0%, respectively. Relations of immunocytochemical profiles against these markers were assessed using panel 34betaE12, GAL-3 and CK19. More than or equal to two of these markers showed co-positive in 53 of 57 PCs, and negative for all markers was observed in only one case. In the other (non PC) cases, the former was 0 of 58 and the latter was 40 cases. In this panel, the sensitivity, specificity and diagnostic accuracy were 93.0%, 100% and 96.8%, respectively. All of these values were higher than or equal to single values of 34betaE12. We concluded that the panel in this study is useful for more objective and accurate diagnosis of thyroid cytology.

Nestin expression as a new marker in malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumor (MPNST) can be difficult to diagnose because it lacks specific immunohistochemical markers. S-100, which is a useful marker of MPNST, has limited diagnostic utility. Recent studies suggest that nestin, which is an intermediate filament protein, is expressed in neuroectodermal stem cells. The diagnostic utility of immunostains for nestin and three other neural markers (S-100, CD56 and protein gene product 9.5 (PGP 9.5)) were evaluated in 35 cases of MPNST and in other spindle cell tumors. All MPNST cases were strongly positive for nestin and had cytoplasmic staining. Stains for S-100, CD56, and PGP 9.5 were positive in fewer cases (17/35, 11/35, and 29/35 cases, respectively), and had less extensive staining. Nestin was negative in 10/10 leiomyomas, and weak nestin expression was seen in 10/10 schwannomas, 3/10 neurofibromas, 2/8 synovial sarcomas, 2/10 liposarcomas, 4/7 carcinosarcomas and 3/7 malignant fibrous histiocytomas. In contrast, strong nestin positivity was seen in 10/10 rhabdomyosarcomas, 15/19 leiomyosarcomas, and 9/9 desmoplastic melanomas. Nestin is more sensitive for MPNST than other neural markers and immunostains for nestin in combination with other markers could be useful in the diagnosis of MPNST.

Quantitative analysis of herpesvirus load in the lymph nodes of patients with histiocytic necrotizing lymphadenitis using a real-time PCR assay.

The cause of histiocytic necrotizing lymphadenitis (HNL) has been ascribed to viral infection, but its pathogenesis still remains unknown. Real-time PCR assays are useful not only for their sensitivity of detection but also for the quantitation of viral DNA with a wide linear range. We accordingly used this technique to estimate for each patient the viral load of the following members of the herpesvirus family: Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus (HHV) types 6, 7, and 8. Samples of patients diagnosed as reactive lymphadenopathy (RL) were included for control. Thirty percent (6/20 cases) and 63% (12/19 cases) of the HNL and RL patients were positive for EBV, and the mean of the detectable EBV viral load of the HNL and that of the RL patients were 463 and 355 (copies/mug DNA), respectively. By in situ hybridization, EBV-encoded RNA could be detected in the lymph tissue samples with more than 14.3 copies/mug of EBV DNA. No significant difference was detected between the number of HNL patients with HHV6 DNA (3/20, 15%) or HHV7 DNA (2/20, 10%) and RL controls. CMV and HHV8 were not detected in the DNA from any patient. In this study, we were unable to definitively identify the causative herpesvirus for HNL; however, 1 HNL case had an extremely large copy number of HHV6-DNA and displayed positive immunostaining for the HHV6 early/late antigen in lesional areas of the node, suggesting that HHV6 infection may be associated with some cases of HNL.