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TAFRO syndrome was first described in 2010, standing for thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly. Because the lymph node histopathology of TAFRO syndrome mimics idiopathic multicentric Castleman disease (iMCD), some researchers consider TAFRO syndrome to be a subtype of iMCD. However, the clinical features of TAFRO syndrome considerably differ from those of iMCD without TAFRO. The clinical features of patients with TAFRO syndrome with or without iMCD-histopathology are similar, and these patients require an accurate diagnosis and urgent treatment. Although a histological diagnosis, including a differential diagnosis, is important, lymph node involvement in patients with TAFRO syndrome is usually modest or sometimes absent. Furthermore, a bleeding tendency due to thrombocytopenia and severe anasarca hampers performing a biopsy. Nonetheless, patients with various other disorders may manifest TAFRO syndrome-like symptoms, making the differential diagnosis in borderline cases difficult. Therefore, the establishment of precise and specific biomarkers is important.

Background and aims Immunoglobulin 4 (IgG4)-related disease (IgG4-RD) is a lymphoproliferative disorder characterized by elevated serum IgG4 levels and tissue infiltration of IgG4-positive plasma cells. We analyzed the serum proteins, whose levels varied based on the disease state and treatment. Materials and methods Serum proteins from patients with IgG4-related disease and healthy subjects were resolved using two-dimensional electrophoresis, silver-stained, and scanned. Alternatively, the proteins were labeled with Cy2, Cy3, and Cy5 before electrophoresis. The proteins, whose expression differed significantly between patients and healthy individuals, and between before and after steroid treatment, were identified and validated using enzyme-linked immunosorbent assays. Results Pre-treatment sera from patients with IgG4-related disease was characterized by increased levels of immunoglobulins such as IgG1, IgG4; inflammatory factors such as α-1 antitrypsin (A1AT); and proteins associated with immune system regulation such as clusterin and leucine-rich α-2-glycoprotein (LRG-1). The serum levels of A1AT, LRG-1 and clusterin, during treatment with prednisolone for up to 12 months revealed that LRG-1 levels were halved after 1 month of treatment, comparable to those in healthy subjects; LRG-1 levels remained normal until the end of treatment. Conclusion LRG-1 could serve as a novel biomarker of IgG4-related diseases.

We report a rare case of xanthomatized Sweet's syndrome with myelodysplastic syndrome (MDS) in a patient who presented with erythematous plaques on his chest that were elevated and became yellowish. A diagnosis of MDS with single lineage dysplasia was made during the development of the eruption. Bone marrow biopsy showed an increased number of megakaryoblasts. Histopathologically, there was neutrophil infiltration with leukocytoclasia and the infiltration of xanthomatous cells. Immunohistochemical analysis revealed that the xanthomatized cells were predominantly CD163 positive. We propose that our case of xanthomatized neutrophilic dermatosis is a rare clinicopathological variant of Sweet's syndrome associated with a hematologic disorder.

Basal cell carcinoma is the most common type of skin cancer, and surgical excision with clear margins is the standard of care. Surgical margins are determined based on risk factors (high or low risk) for recurrence according to the National Comprehensive Cancer Network and Japanese basal cell carcinoma guidelines. The clarity of the clinical tumor border (well-defined or poorly defined) is considered a risk factor, and significant discrepancies in the judgment of clinical tumor borders among dermato-oncologists may occur. Therefore, we analyzed the dermato-oncologists' concordance in judging the clinical tumor border of basal cell carcinoma. Forty-seven dermato-oncologists (experts: 37; young trainees: 10) participated in this study. The datasets of clinical and dermoscopic photographs of 79 Japanese cases of head and neck basal cell carcinoma were used to determine the concordance in the judgment of clinical tumor border. The probability of the border that was selected more often was used to calculate the rater agreement rate for each dataset. Correct judgment was defined as a more frequently selected border, and the concordance rate of clarity of clinical tumor border for each dermato-oncologist was calculated based on the definition of the correct judgment. A median concordance rate of 85% or higher for all dermato-oncologists was predefined as an acceptable rate for clinical use. Of the 79 datasets, rater agreement rates were 80-100%, 60-79%, and 51-59% for 55, 19, and five datasets, respectively. The median concordance rate for all dermato-oncologists was 86% (interquartile range: 82-89%). There was no significant difference in the concordance rate between the experts and the trainees (median, 87% vs. 85.5%; p = 0.58). The concordance rates of dermato-oncologists for all datasets were relatively high and acceptable for clinical use.

TAFRO syndrome is a systemic inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. Mortality in patients with this syndrome is high; however, an optimal treatment strategy has not been established. To explore the strategy, we retrospectively analyzed 81 patients with TAFRO syndrome registered in the Multicenter Collaborative Retrospective Study for Establishing the Concept of TAFRO Syndrome in Japan by December 2019. Sixty-eight patients received corticosteroid therapy as the first-line treatment, and as the second-line treatment, 21 received tocilizumab (Toc), 14 received cyclosporine A (CsA), and 8 received rituximab (Rit) in addition to corticosteroids. We compared these second-line treatment groups by setting the primary endpoint as time to next treatment or death (TTNT). Kaplan–Meier analysis showed that the median TTNT in the Toc, CsA, and Rit groups were 2.8 months, 9.2 months, and not reached, respectively. The TTNT of the Rit group was significantly longer than that of the Toc group. In contrast, there were no significant differences in overall survival between groups, indicating that subsequent salvage therapies rescued a large proportion of patients who failed the second-line treatments. Further studies are warranted to establish the optimal treatment strategies for this syndrome.

Various systems for predicting the prognosis of patients with myelodysplastic syndromes (MDS) have been developed. However, associations between performance status (PS) and prognosis of MDS require further investigation. To objectively assess the impact of PS on survival, we examined laboratory findings associated with PS, including serum levels of C-reactive protein (CRP), albumin (ALB), and total cholesterol (CHOL). Patients (n = 123; male 86, female 37; median age 74 yrs.) diagnosed with MDS or myelodysplastic/myeloproliferative neoplasms at Kanazawa Medical University Hospital between 2010 and 2020 were enrolled and grouped by cutoff values determined by receiver operating characteristic analysis: 0.44 mg/dL for CRP, 4.0 g/dL for ALB, and 120 mg/dL for CHOL. The median follow-up period was 17.6 months. Kaplan-Meier analysis revealed that overall survival (OS) in the high CRP, low ALB, and low CHOL groups was significantly shorter than in the low CRP, high ALB, and high CHOL groups, respectively. Multivariable analysis revealed that elevated serum CRP was an independent prognostic risk factor independent of gender, bone marrow blast percentage, and cytogenetics.

To identify prognostic factors for TAFRO syndrome, a rare inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. Data of patients with TAFRO syndrome were extracted from a Japanese patient registry. Patients were divided into groups according to the clinical and laboratory parameters at initial presentation. Cut-off values for the laboratory parameters were determined using receiver operating characteristic curve analysis and by clinical relevance. Patient survival was analyzed by the Kaplan–Meier method. Univariable analysis was performed using log-rank tests. Multivariable analyses were performed with the logistic regression model and the Cox-proportional hazards model. We extracted the data of 83 patients with TAFRO syndrome from the registry. Univariable analysis identified several potential prognostic factors. Of these factors, age ≥ 60 years and D-dimer ≥ 18 μg/dL remained significant predictors of poor overall survival in the multivariable Cox-proportional hazards model. Based on these results, we developed a simple prognostic scoring system for TAFRO syndrome (TS-PSS). Patients in our cohort were stratified into low, intermediate, and high-risk groups by the TS-PSS. This system should be verified with independent patient cohorts in future studies. Supplementary Information The online version contains supplementary material available at 10.1007/s12185-021-03159-x.

Evaluation of tissue margins and hemodynamics is necessary during macropathology of skin lesions. This study aims to produce saliency maps of skin chromophores from ex-vivo specimens and observe the effect of formalin fixation on the maps. We used a multi-spectral imaging system with narrow-band illumination to capture various skin lesions. Saliency maps were produced with three different methods adapted from the literature by utilizing spectral absorption and absorption slope. Saliency maps derived from fixed and unfixed tissue were registered and subsequently compared in terms of correlation and histogram similarity. Preliminary results show high dissimilarity between maps of fixed and unfixed tissue, highlighting the influence of formalin fixing on hemodynamics, while relative distribution of melanin remained mostly unaffected.

This study reports on the development of a high-resolution 4K multispectral camera designed to enhance telepathology support systems for remote gross-pathological diagnosis. We experimentally examine and evaluate the camera’s effectiveness in three subjects: the reconstruction of precise color images, the emphasis of cancerous tissue areas, and pre-fixed image reproduction from fixed images. The evaluation results of the first and second subjects showed that the camera and supporting methods could be effectively used in gross pathology diagnosis. The images obtained in the third subject received positive evaluations from some pathologists, but others expressed reservations as to its utility.

TAFRO syndrome is a systemic inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. Mortality in patients with this syndrome is high; however, an optimal treatment strategy has not been established. To explore the strategy, we retrospectively analyzed 81 patients with TAFRO syndrome registered in the Multicenter Collaborative Retrospective Study for Establishing the Concept of TAFRO Syndrome in Japan by December 2019. Sixty-eight patients received corticosteroid therapy as the first-line treatment, and as the second-line treatment, 21 received tocilizumab (Toc), 14 received cyclosporine A (CsA), and 8 received rituximab (Rit) in addition to corticosteroids. We compared these second-line treatment groups by setting the primary endpoint as time to next treatment or death (TTNT). Kaplan-Meier analysis showed that the median TTNT in the Toc, CsA, and Rit groups were 2.8 months, 9.2 months, and not reached, respectively. The TTNT of the Rit group was significantly longer than that of the Toc group. In contrast, there were no significant differences in overall survival between groups, indicating that subsequent salvage therapies rescued a large proportion of patients who failed the second-line treatments. Further studies are warranted to establish the optimal treatment strategies for this syndrome.

A subcutaneous tumor accompanied by tenderness has a myriad of differential diagnoses. Indeed, using physical findings alone to achieve a diagnosis is often challenging. In this study, we focused on schwannomas and angioleiomyomas, which usually develop as hard subcutaneous tumors and are often associated with tenderness. We aimed to determine significant differentiating features between the tumor types, using ultrasonography. We compared clinical findings and ultrasonographic imaging and calculated the statistical significance for each item. In total, we analyzed 11 schwannomas and 13 angioleiomyomas of the extremities, trunk and head. There was no significant difference in patient characteristics or clinical findings. Meanwhile, the mean maximum diameter (P = 0.002), localization (P = 0.04) and entering or exiting nerves (P = 0.01) were significantly different according to ultrasonography findings. Thus, ultrasonography provides excellent information for the initial assessment of a slow-growing, painful, subcutaneous soft tissue mass. According to our study, it is difficult to identify a single, differentiating feature between angioleiomyoma and schwannoma on ultrasonography, but including multiple findings during the work-up can facilitate differential diagnosis.

A cutaneous metastatic tumor is relatively rare, and patients with such a tumor usually have a poor prognosis. Even if the metastases can be treated, the treatment cannot improve the prognosis. However, neglecting metastatic lesions sometimes results in a great deterioration of quality of life. Cutaneous metastatic foci are generally treated with chemotherapy and/or radiotherapy. On the other hand, surgical treatment is sometimes chosen for cutaneous metastases. In this study, we analyzed data for 40 patients with cutaneous metastatic tumors who received surgical treatment at Shizuoka Cancer Center between January 2009 and August 2014. Among these cases, lung cancer was the most common primary cancer and the craniocervical region was the most frequent metastatic site. Among the patients who died, the average duration to death after the operation was 186 days. We consider that resection of cutaneous metastatic tumors as palliative therapy is an appropriate therapeutic option if the patient's condition permits resection. Such treatment can improve quality of life for both the patients and their families.

Although cutaneous angiosarcoma (cAS) has one of the worst prognoses among malignant skin tumors, few effective drug options for secondary treatment have been discovered to date because of the limited number of cases. Therefore, this study was aimed at determining pazopanib’s potential as a new cAS treatment option. We retrospectively evaluated five patients with taxane-resistant unresectable cAS treated with pazopanib at a university hospital. Their characteristics and treatment outcomes were retrieved from their records. Progression-free survival (PFS), overall survival (OS), disease progression, and toxicity were evaluated; furthermore, the response to pazopanib was assessed in relation to the expression of vascular endothelial growth factor receptor 2 (VEGFR-2). The median PFS from the time of pazopanib initiation was 94 days. Two patients showed partial response, two showed stable disease, and one had progressive disease in the case of the best overall response. VEGFR-2 expression was positive in all cases, and patients with high expression had improved median OS compared to that in those with low expression. VEGFR-2 expression was correlated with a longer OS. The most common toxicities were hypertension and anorexia followed by myelosuppression. This is the largest case series reported wherein pazopanib was used for taxane-resistant cAS. Although the cytoreductive effect and survival benefits were not significant in this small sample, we consider pazopanib a valid treatment option for preserving patients’ quality of life. Our results suggest pazopanib treatment slows the progression of disease and stabilizes it in patients with taxane-resistant cAS.