Psoriasis-like skin rash triggered by a local infection in a patient with eosinophilic granulomatosis with polyangiitis that was well controlled by mepolizumab treatment.

Key Clinical message: A patient with eosinophilic granulomatosis with polyangiitis, who was well-controlled by pharmacotherapy, developed a psoriasis-like rash due to a local infection. It represents the consequence of an immunologic imbalance. Abstract: A 48-year-old woman was diagnosed with eosinophilic granulomatosis with polyangiitis and treated with mepolizumab. While on treatment, she developed a psoriasis-like rash on her lower legs following a local ear infection. The rash promptly disappeared after the ear infection cleared and did not recur. The psoriasis-like rash that appeared was pathologically similar to psoriasis. Excessive production of inflammatory cytokines by the immune system is believed to be involved in the pathogenesis of psoriasis vulgaris. These cytokines are known to induce inflammatory responses and promote epidermal cell proliferation. It is possible that mepolizumab treatment suppressed Th2-type cytokines, while the local ear infection temporarily induced a strong Th1-type immunity. This immunologic imbalance may have led to the development of a psoriasis-like rash.

Diagnostic Utility of TUNEL Staining for Degenerative Keratoacanthoma Requiring Pathologic Differentiation from Seborrheic Keratosis.

Tumors developed in 2 old women presented with pathological findings similar to seborrheic keratosis, although the clinical feature of tumor showed typical keratoacanthoma. In addition to these two cases, we compared the pathological findings of a total of four cases, one case each of keratoacanthoma and seborrheic keratosis, which were clinically and histopathological typical. These two cases and the typical keratoacanthoma showed cell apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and infiltration of cytotoxic T cells. The keratoacanthoma in the decompensated stage may be histologically similar to seborrheic keratosis. TUNEL staining can help in the diagnosis of fading keratoacanthoma.

Surgical outcomes of the Frey procedure for chronic pancreatitis: correlation between preoperative characteristics and the histological severity of pancreatic fibrosis.

PURPOSE: To evaluate the efficacy of the Frey procedure and clarify the relationship between preoperative characteristics and the histological severity of chronic pancreatitis (CP). METHODS: Thirty patients who underwent the Frey procedure for CP between January, 2002 and December, 2020, at our hospital, were enrolled in this study. The specimen cored out of the pancreatic head was assessed for CP severity. We evaluated preoperative status and surgical outcomes according to CP severity. RESULTS: Long-term pain relief was achieved in all 26 patients with sustained long-term follow-up, with complete pain relief attained in 19 (63%). Albumin levels were significantly higher 1 year postoperatively than preoperatively (p = 0.038). Histological fibrosis was assessed in the 26 patients as follows: normal (n = 4; 15%), mild (n = 8; 31%), moderate (n = 2; 8%), and severe (n = 12; 46%). These patients were divided into two groups according to the severity of fibrosis: normal/mild (n = 12) and moderate/severe (n = 14). The rates of diffuse calcification on preoperative computed tomography (CT) (71% vs. 17%, p = 0.008) and islet atrophy on insulin immunohistochemistry (100% vs. 33%, p < 0.001) were significantly higher in the moderate/severe group than in the normal/mild group. CONCLUSION: The Frey procedure can achieve good pain relief and improve nutritional status. The severity of fibrosis can be predicted based on the extent of calcification on preoperative imaging studies.

Treatment Strategy for Pyoderma Gangrenosum: Skin Grafting with Immunosuppressive Drugs.

Pyoderma gangrenosum (PG) is a relatively rare neutrophilic dermatosis presenting as a rapidly progressive and painful skin ulcer characterized by undermined borders and peripheral erythema. Immunosuppressive therapy is the first-line treatment for PG; however, large ulcers often take months or years to heal. Surgical treatments, such as negative pressure wound therapy (NPWT) and skin grafting, are still controversial due to the risk of inducing the pathergy phenomenon and eliciting PG development by traumatic factors. Herein, we report on four cases of PG treated with skin grafting, with or without NPWT, under the control of immunosuppressive drugs at our institution. All cases adapted well, but one case showed recurrence at the periphery of the grafted area five months postoperatively. The current patients were treated with the following doses of oral prednisolone (PSL): PSL 10 mg daily, PSL 5 mg daily + adalimumab 40 mg/week, PSL 12 mg + 6 mg of tacrolimus daily, and PSL 20 mg daily during skin grafting. No severe complications, including infections, were observed. Surgical treatments, such as skin grafting with or without NPWT, may accelerate wound healing, shorten the administration of analgesics and long-term immunosuppressive therapy, and reduce the risk of infection.

Successful treatment with cyclosporine and guselkumab for pityriasis rubra pilaris.

A man with pityriasis rubra pilaris (PRP) showed no improvement in skin symptoms despite treatment with several drugs. The patient was diagnosed as having type 1 PRP. Combination therapy with cyclosporine and guselkumab improved his skin condition. Here, we propose a novel therapeutic strategy for intractable PRP.

Biliary obstruction caused by plant seeds.

Biliary obstruction is rarely caused by foreign objects; therefore, the precise diagnosis may be challenging. Even in rare situations, cases of biliary obstruction caused by plant seeds have not been reported previously. To our knowledge, herein, we report the first case of biliary obstruction caused by accumulated plant seeds forming a solid mass with inflammatory cells and bile juice, which were identified as Solanum lycopersicum, Brassica, and Citrus species by DNA analysis and pathological assessment of the specimen after surgical resection for biliary obstruction suggestive of cholangiocarcinoma.

A Case of Adult-Onset Eccrine Angiomatous Hamartoma-The Comparison with Epithelioid Hemangioma.

Eccrine angiomatous hamartoma (EAH) is a relatively rare benign skin disease characterized by the proliferation of eccrine sweat glands associated with capillary hemangioma and the proliferation of other skin elements such as adipose tissue, hair, and epidermis. The onset of the disease is usually at birth or in childhood and tends to occur in the extremities of females, but it occurred in an adult male in this case. The patient was a 72-year-old man with a 12 × 12 mm light brown, elastic, slightly firm skin nodule on the flexor aspect of his right forearm. A biopsy revealed enlargement of blood vessels, sweat glands, sweat ducts, and erector spongiosum with both lumen dilation and narrowing, leading to the diagnosis of EAH. The histopathological features of EAH include a marked proliferation of microvessels, epithelial-like changes in vascular endothelial cells (such as enlarged nuclei), and infiltration of inflammatory cells, mainly lymphocytes and plasma cells. In adult-onset cases, EAH can be clinically difficult to distinguish from epithelioid hemangioma (EH), which differs in the predominance of microvascular proliferation and the presence of eosinophils in the infiltrating inflammatory cells. It can also be distinguished from EAH by the negative results of S100 and anti-EMA in immunohistological staining. In the current cases, we were able to differentiate the two cases from characteristic findings on HE staining.

A new detection system for serum fragmented cytokeratin 18 as a biomarker reflecting histologic activities of human nonalcoholic steatohepatitis.

Caspase-generated fragmented cytokeratin 18 (fCK18) is recognized as a useful noninvasive biomarker in the diagnosis of nonalcoholic fatty liver disease (NAFLD), particularly nonalcoholic steatohepatitis (NASH). However, fCK18 measurement is not applied clinically due to widely variable cut-off values under the current enzyme-linked immunosorbent assay platform. Therefore, we developed a highly sensitive chemiluminescent enzyme immunoassay using newly developed monoclonal antibodies against fCK18 and investigated its relevance in NASH diagnosis. Serum fCK18 levels were measured in the derivation and validation cohort. The correlation between serum fCK18 levels and NAFLD activity score (NAS), fibrosis stage, and liver function was examined. Serum fCK18 levels were significantly correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase. Serum fCK18 levels were significantly associated with NAS, Brunt's grade/stage, Matteoni's classification, portal inflammation, and fat accumulation in the liver. Notably, hepatocyte ballooning was the only independent variable significantly associated with serum fCK18 in the multivariate linear regression analysis. Serum fCK18 levels were significantly elevated in patients with NAFLD and nonalcoholic fatty liver (NAFL) compared to healthy individuals. They were also significantly elevated in patients with NAFL compared to NASH defined by NAS or Matteoni's classification, with area under the curve values being 0.961 (NAFLD vs. healthy), 0.913 (NAFL vs. healthy), 0.763 (NASH vs. NAFL), and 0.796 (NASH type 3-4 vs. NAFL type 1-2). These results were confirmed by a validation cohort. Notably, changes over time in serum fCK18 levels were significantly correlated with changes in ALT, AST, and the fibrosis-4 index in 25 patients who underwent lifestyle modification. Serum fCK18 levels were significantly correlated with liver damage associated with NASH pathology. Serum fCK18 levels are accurate in distinguishing patients with NAFL or NASH from healthy individuals and may be useful to monitor NASH over time.

Eosinophilic fasciitis induced by a game of drumming probably via type 2 innate immunity.

We report a case of eosinophilic fasciitis triggered by strenuous physical activity, which did not relapse during the follow-up period. We ascertained that interleukin-33 (IL-33) was released from the vascular endothelial cells after intense exercise, inducing type 2 innate lymphocytes (ILC2) and causing fasciitis. A healthy woman experienced itching on both limbs a few hours after a game of drumming. Her hand, knee joints, and legs gradually swelled up with groove signs along the superficial veins. White blood cell and eosinophil counts were significantly elevated. Magnetic resonance imaging revealed a high signal at the fascia on both lower limbs. Histopathological findings of the left lower limb tissue specimen showed edematous fascia with eosinophils. No relapse of eosinophilic fasciitis was observed after finishing treatment with prednisolone. Immunological staining for IL-4, IL-5, IL-33, tumor necrosis factor-α, and interferon-γ was performed on the fascial tissue. Both IL-4 and IL-5 were stained on the lymphocytes at the muscle and fascia levels; however, CD3 and CD4 were unstained in these cells, suggesting that those cells were ILC2. Tumor necrosis factor-α and interferon-γ were unstained. Vascular endothelial cells in the fascia strongly expressed IL-33. Eosinophilic fasciitis may be associated with type 2 immunity triggered by IL-33 in the current case.

Case Report: A Difficult-to-Diagnose Case of Hyperinsulinemic Hypoglycemia Surgically Treated After Developing Acute Pancreatitis.

The patient is a 28-year-old Japanese man diagnosed with severe congenital hyperinsulinemic-hypoglycemia six months after birth. Clinical records revealed no imaging evidence of pancreatic tumor at the time of diagnosis. Subsequently, he had developmental disorders and epilepsy caused by recurrent hypoglycemic attacks. The patient's hypoglycemia improved with oral diazoxide. However, he developed necrotizing acute pancreatitis at 28 years of age, thought to be due to diazoxide. Discontinuation of diazoxide caused persistent hypoglycemia, requiring continuous glucose supplementation by tube feeding and total parenteral nutrition. A selective arterial secretagogue injection test revealed diffuse pancreatic hypersecretion of insulin. He underwent subtotal distal (72%) pancreatectomy and splenectomy. There was no intraoperative visible pancreatic tumor. His hypoglycemia improved after the surgical procedure. The histopathological study revealed a high density of islets of Langerhans in the pancreatic body and tail. There were large islets of Langerhans and multiple neuroendocrine cell nests in the whole pancreas. Nests of neuroendocrine cells were also detected in lymph nodes. The pathological diagnosis was grade 1 neuroendocrine tumor (microinsulinomas) with lymph node metastases. This patient is a difficult-to-diagnose case of hyperinsulinemic hypoglycemia surgically treated after developing acute pancreatitis. We believe this is a unique case of microinsulinomas with lymph metastases diagnosed and treated as congenital hyperinsulinemic hypoglycemia for almost 28 years.

Three Cases of Lymphocytic Infiltration of the Eyelid.

Lymphocytic infiltration of the skin (LIS), first reported by Jessner and Kanof in 1953, is a disease of unknown etiology characterized by erythematous papules and plaques on the head, neck, and upper back and histopathological findings of a normal epidermis with underlying lymphocytic infiltration of the reticular dermis without mucin deposition. A 69-year-old man and a 21-year-old woman presented with edematous indurative erythema of the left upper eyelid. Lymphocytic infiltration of the dermis with CD4+ T cell predominance was noted on biopsy. A 68-year-old man presented with a four-year history of recurrent edematous indurative erythema of the right upper eyelid that extended up to the right cheek. Predominantly dermal infiltration of CD8+ T lymphocytes was found on biopsy. We treated all three patients with 8-16 mg of methylprednisolone daily, and the erythema and induration improved. CD4+ T cells were predominant in the acute phase (patients 1 and 2), whereas CD8+ T cells were predominant in the chronic phase (patient 3). CD8+ T cells may be involved in LIS recurrence. Lymphocytic infiltration of the eyelid may be associated with isolated circumscribed, edematous, indurative, colorless lesions that are responsive to daily low-to-middle doses of oral methylprednisolone.

Three-dimensional structure analysis of melanocytes and keratinocytes in senile lentigo.

Senile lentigo or age spots are hyperpigmented macules of skin that commonly develop following long-term exposure to ultraviolet radiation. This condition is caused by accumulation of large numbers of melanosomes (melanin granules) produced by melanocytes within neighboring keratinocytes. However, there is still no consensus regarding the melanosome transfer mechanism in senile lentigo. To date, most pathohistological studies of skin have been two-dimensional and do not provide detailed data on the complex interactions of the melanocyte-keratinocyte network involved in melanosome transfer. We performed a three-dimensional reconstruction of the epidermal microstructure in senile lentigo using three different microscopic modalities to visualize the topological melanocyte-keratinocyte relationship and melanosome distribution. Confocal laser microscopy images showed that melanocyte dendritic processes are more frequently branched and elongated in senile lentigo skin than in normal skin. Serial transmission electron micrographs showed that dendritic processes extend into intercellular spaces between keratinocytes. Focused ion beam-scanning electron micrographs showed that dendritic processes in senile lentigo encircle adjacent keratinocytes and accumulate large numbers of melanosomes. Moreover, melanosomes transferred to keratinocytes are present not only in the supranuclear area but throughout the perinuclear area except on the basal side. The use of these different microscopic methods helped to elucidate the three-dimensional morphology and topology of melanocytes and keratinocytes in senile lentigo. We show that the localization of melanosomes in dendritic processes to the region encircling recipient keratinocytes contributes to efficient melanosome transfer in senile lentigo.

Voriconazole-Induced Squamous Cell Carcinoma after Hematopoietic Stem Cell Transplantation Showing Early-Stage Vascular Invasion.

Voriconazole is a triazole antifungal agent used for the prevention and treatment of fungal infections in immunocompromised patients. Prolonged voriconazole therapy may induce phototoxicity and lead to the development of malignant neoplasms of the epidermis, such as squamous cell carcinoma (SCC), especially in immunocompromised patients. We report a case of voriconazole-induced phototoxicity and SCC occurring after hematopoietic stem cell transplantation (HSCT) in a 56-year-old man with primary myelofibrosis. The patient developed chronic graft-versus-host disease (GVHD) post-transplantation and had been receiving long-term immunosuppressive treatment. A year after the initiation of voriconazole therapy for prophylaxis, he developed keratotic erythema, followed by SCC with vascular invasion after three years. A review of SCC in HSCT recipients suggests that the prolonged use of voriconazole is regarded as a risk for SCC after HSCT in patients with chronic GVHD on immunosuppressive therapy. Moreover, a histological examination of the completely resected tumor revealed vascular invasion in this case, although neither the clinical features nor the histological findings of the preoperative biopsy suggested invasive carcinoma. This case may partially explain why voriconazole-associated SCCs show a more aggressive clinical course than non-voriconazole SCCs do.

Soluble programmed death-ligand 1 rather than PD-L1 on tumor cells effectively predicts metastasis and prognosis in soft tissue sarcomas.

The soluble form of PD-L1 (sPD-L1) is related to a poor prognosis in various cancers. Comparisons of sPD-L1 and PD-L1 expressed on tumor cells in soft tissue tumor patients have not been reported. The purpose of this study was to analyze serum sPD-L1 and PD-L1 levels in soft tissue tumor patients. A total of 135 patients with primary soft tissue tumors were enrolled in this study. The sPD-L1 level was quantitatively measured by enzyme immunoassay, and PD-L1 expression on high grade sarcoma cells was analyzed immunohistologically. There were no significant differences in sPD-L1 levels between benign (48) and soft tissue sarcoma (STS) patients (87). In STS, the high sPD-L1 (>44.26 pg/mL) group had significantly lower metastasis-free survival (MS) and lower overall survival (OS) than the low sPD-L1 group (≤44.26 pg/mL) at 5 years using the log-rank test. On multivariate Cox proportional hazard analysis, the high sPD-L1 group had significant differences in MS and OS compared to the low sPD-L1 group. Between positive and negative immunostaining groups, recurrence-free survival (RS), MS, and OS were not significantly different. No correlation was found between immunostaining and sPD-L1 with the Kappa coefficient. The sPD-L1 concentration could predict future metastasis and prognosis in STS patients. High sPD-L1 in STS patients may be a target for treatment with checkpoint inhibitors.

Achievement of long-term remission of disseminated histoplasmosis in an AIDS patient.

Histoplasmosis, a fungal infection caused by Histoplasma capsulatum, is poor prognosis once it disseminated, especially in immunocompromised patients. A 50-year-old Japanese-Brazilian male with multiple cervical lymphadenopathies was diagnosed as disseminated histoplasmosis and acquired immunodeficiency syndrome (AIDS). Anti-fungal therapy was initiated followed by anti-retroviral therapy (ART). He achieved long-term remission by treatment with voriconazole. Here we report a case of an AIDS patient with disseminated histoplasmosis who achieved long-term survival in non-endemic area.

Psoriasiform Dermatitis Developing during Treatment of Juvenile Idiopathic Arthritis with Tocilizumab.

We present a case of psoriasiform dermatitis developing during the treatment of juvenile idiopathic arthritis with tocilizumab (TCZ). The keratotic erythema with central healing showed a periodicity of growing worse 1 week after TCZ infusion, and then disappeared within 3 weeks. Skin biopsy showed parakeratosis, microabscess, rete ridge elongation, and abundant lymphocytes as well as a few neutrophil infiltrate in the upper dermis. TCZ is a humanized monoclonal antibody against interleukin 6 (IL-6) receptor. IL-6 plays a critical role in the differentiation from naïve T cells into Th17 cells in cooperation with transforming growth factor-ß. IL-6 may be important in psoriasis pathogenesis, and therefore this phenomenon may be the adverse effect. The mechanism of TCZ-associated psoriasiform dermatitis is unclear. The serum IL-6 level seems to be elevated transitorily after TCZ administration, probably due to the competitive inhibition of IL-6 receptor alpha to IL-6. Excess free IL-6 may effect on other IL-6 family receptors. Since TCZ does not alter serum IL-17F level, another cytokine may be involved in the psoriasis formation in our case. Psoriasiform dermatitis during the use of TCZ may be due to relative cytokine balance disturbance.

A case of hepatic anisakiasis caused by Pseudoterranova decipiens mimicking metastatic liver cancer.

BACKGROUND: Anisakid nematodes (Anisakis spp. or Pseudoterranova spp.) usually infect gastric or intestinal walls, while they rarely infect in extra-gastrointestinal sites of human body. Generally, Anisakis spp. larvae are highly infected in fish intermediate hosts, whereas Pseudoterranova spp. larvae are very rarely infected. To the best of our knowledge, there have been no reports which have documented cases of hepatic anisakiasis caused by Pseudoterranova spp. This report describes the first documented case of hepatic anisakiasis due to infection with Pseudoterranova decipiens and clinical features of the hepatic anisakiasis through literature review. CASE PRESENTATION: The case was a 28-year-old man with prior history of malignancy who was found to have a hepatic mass mimicking metastatic liver tumor. A new low density area of 20 mm in diameter in liver segment 7 was found on follow-up CT. With suspicious diagnosis of metastatic liver cancer, laparoscopic partial hepatectomy was performed. A pathological examination revealed no evidence of malignancy, but showed necrotic granuloma with eosinophil infiltration and the presence of a larva with Y-shaped lateral cords, which are specific to anisakid larvae. The type of larva was identified as Pseudoterranova decipiens sensu lato using PCR of DNA purified from a fixed granuloma embedded in paraffin. CONCLUSION: The present report is the first to discuss the case of a patient with hepatic anisakiasis caused by Pseudoterranova decipiens. Hepatic anisakiasis is a potential differential diagnosis for hepatic tumors and genetic identification with the PCR method was reliable for obtaining final diagnosis even when the larvae body in the resected specimen collapses with time.

Cytological features of adenocarcinoma admixed with small cell neuroendocrine carcinoma of the uterine cervix.

Adenocarcinoma admixed with neuroendocrine carcinoma of the uterine cervix is a rare malignancy with a poor prognosis, and few reports have described the cytological features of this carcinoma. To characterize the cytological features of this malignancy in cervical smears, we report a case of a 52-year-old Japanese woman with cervical adenocarcinoma admixed with small cell neuroendocrine carcinoma (SCNEC). Cytologically, there were two types of cells with different sizes. The smaller cells formed clusters, which showed a partially Indian file pattern, a high nuclear/cytoplasmic ratio, and hyperchromatic nuclei. In contrast, the larger cells showed cytological features of adenocarcinoma, indicating a glandular-like pattern. Histological examination of biopsy specimens revealed that the tumors were composed of almost equal areas of SCNEC and adenocarcinoma. Neuroendocrine differentiation was confirmed by immunohistochemistry for synaptophysin and CD56. Thus, when adenocarcinoma cells are detected in smears, attempts to search for SCNEC cells should be made by combined cytological and histological analyses in order to reach an accurate diagnosis of the carcinoma in the uterine cervix.