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We herein report a fatal case of coronavirus disease 2019 (COVID-19) pneumonia with rapid progression of respiratory failure and lymphopenia. Excessive recruitment and sequestration of lymphocytes in the lung were suggested as the pathophysiology underlying COVID-19-associated lymphopenia. Interestingly, the autopsy in this case revealed lymphocytic infiltration in the lungs even at sites that appeared normal on autopsy imaging. These findings suggest that in COVID-19 cases with risk factors of severe exacerbation, early glucocorticoid administration should be considered, especially if lymphopenia is present, even if the imaging findings show only mild abnormalities.

Histologic transformation has been described as an acquired mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We herein report the case of a woman with stage IV lung adenocarcinoma harboring EGFR exon 19 deletions who was initially treated with EGFR-TKIs; several cytotoxic chemotherapeutic regimens were used when resistance developed. A lymph node re-biopsy revealed histologic transformation of the tumor to combined small-cell lung cancer and squamous cell carcinoma with retained EGFR exon 19 deletions. Following sequential chemotherapy appropriate for transformed histology, a clinical response was achieved.

Multiple thymic carcinoids are rare, and giant cell arteritis (GCA) is one of the less recognized paraneoplastic diseases. The co-occurrence of these two diseases is therefore extremely rare. We report herein a patient with multiple atypical thymic carcinoids and asymptomatic paraneoplastic GCA. All the thymic carcinoids were diagnosed histopathologically as atypical thymic carcinoids with an intrathymic metastasis. Treatment consisted of a complete tumor resection followed by observation of the GCA without any adjuvant therapy. Subsequent positron emission tomography revealed a decrease in F-fludeoxyglucose accumulation in the systemic arteries. Based on these findings, paraneoplastic GCA was diagnosed. Thymic carcinoids rarely involve intrathymic metastasis or cause neopleonastic GCA. However, when they do, a complete tumor resection is the best option for management.

Histologic transformation has been described as an acquired mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We herein report the case of a woman with stage IV lung adenocarcinoma harboring EGFR exon 19 deletions who was initially treated with EGFR-TKIs; several cytotoxic chemotherapeutic regimens were used when resistance developed. A lymph node re-biopsy revealed histologic transformation of the tumor to combined small-cell lung cancer and squamous cell carcinoma with retained EGFR exon 19 deletions. Following sequential chemotherapy appropriate for transformed histology, a clinical response was achieved.

A 43-year-old woman presented with worsening shortness of breath and lower-extremity edema. Echocardiography and computed tomography showed obstruction of blood flow due to a mass filling the right atrium. Emergency surgery was performed for circulatory failure. Primary cardiac rhabdomyosarcoma was diagnosed based on a histological examination. The patient died about two months after the diagnosis despite surgical excision and radiation therapy. The poor prognosis may have resulted from the grossly incomplete removal of the tumor and chemotherapy intolerance. We herein report a case of primary cardiac rhabdomyosarcoma filling the right atrium and offer possible reasons for the poor prognosis.

Peripartum cardiomyopathy (PPCM) is a rare disorder in which left ventricular (LV) systolic dysfunction and symptoms of heart failure (HF) occur in the peripartum period. The time to potential recovery from severe remodeling of ventricular function is difficult to predict. Although lack of late gadolinium enhancement (LGE) in cardiovascular magnetic resonance (CMR) is reportedly associated with functional recovery of the LV in some cardiomyopathies, the impact of LGE in PPCM remains unclear. We herein report a case of a patient with PPCM who demonstrated rapidly worsened ventricular function, leading to requirement of a paracorporeal left ventricular assist device (LVAD) implantation despite absence of LGE in CMR. A 34-year-old Japanese patient, G2P2A0, expecting her third delivery following a full-term pregnancy, experienced heart failure. Severe LV dysfunction and PPCM were diagnosed. CMR showed no LGE. Although standard HF therapy and bromocriptine were given, her cardiac function failed to recover, and she eventually underwent paracorporeal LVAD implantation as a bridge to heart transplantation due to the impossibility of stopping the administration of inotropic agents.

Objective To investigate the relationship between the precursors of high grade serous ovarian cancer (HGSOC) and the characteristics of patients with a low HGSOC risk in terms of the effects of pregnancy. Methods We prospectively examined consecutive cases in which the bilateral fallopian tubes were removed during benign gynecological or obstetric surgery and assessed the relationship between the patient characteristics, including parity and pregnancy, and the incidence of HGSOC precursors. All the fallopian tubes were examined by applying the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) Protocol. Results Of the 113 patients enrolled, 67 were gynecological and 46 were obstetric. The p53 signature was identified in 21 patients. No other precursors were identified. In a comparison of the p53 signature-positive and negative groups, parous women and pregnant women were significantly fewer in the p53 signature-positive group (53% vs. 86%, p=0.002, 10% vs. 47%, p=0.001, respectively). Current pregnancy was also associated with a significantly lower incidence of the p53 signature after multivariate adjustment (odds ratio [OR]=0.112; 95% confidence interval [95% CI]=0.017-0.731; p=0.022). Among gynecological patients, parous women were fewer in the p53 signature-positive group on univariate (47% vs. 73%, p=0.047) and multivariate analysis (OR=0.252; 95% CI=0.069-0.911; p=0.036). No other characteristics were associated with p53 signature positivity. Conclusions The incidence of the p53 signature was significantly lower in parous women and pregnant women. This decreased incidence of early phase serous carcinogenesis may be one of the possible mechanisms underlying HGSOC risk reduction among parous women.

A 62-year-old man with myelodysplastic syndrome (MDS) presented to our hospital with a high fever. Although treatment with broad-spectrum antibiotics was initiated, his respiratory status worsened to the point that he required mechanical ventilation. However, he was successfully treated with a corticosteroid without immunosuppression. Sequential transbronchial lung biopsies revealed abundant fibrin exudate in the alveolar spaces, which was subsequently replaced by fibroblasts, showing that acute fibrinous and organizing pneumonia (AFOP) gradually changes into organizing pneumonia. Our case demonstrated both the efficacy of corticosteroid-monotherapy and the histological course of AFOP.

A Peutz-Jeghers polyp (PJP) is a hamartomatous lesion characterized by arborescent smooth muscle bundles covered with mucosa native to the site of involvement. PJPs in the small intestine may represent misplacement of non-neoplastic epithelium into the submucosa, muscularis propria and subserosa. Although epithelial misplacement in PJPs is a well-documented phenomenon, pseudoinvasion even into the vascular space in PJPs has not previously been reported. We report a case of a 22-year-old Japanese woman with a solitary PJP in the ileum. The ileal PJP in this patient showed epithelial herniation even into the vascular space. All the herniated epithelium, including the epithelial components invaginated into the vascular space, demonstrated features of pseudoinvasion, that is, presence of normal small intestinal type mucosa accompanied by the lamina propria, absence of any stromal desmoplastic reaction, and retention of the basal-luminal gradient. Pathologists must be aware of the possibility of vascular pseudoinvasion in small intestinal PJPs to avoid overdiagnosis of carcinoma and resulting unnecessary major surgery.

A previously healthy 61-year-old man was admitted to our hospital in June, 2014, with a 3 week history of low-grade fever, general fatigue, and dyspnoea on exertion. He denied weight loss, abdominal pain, changes in bowel habit, or bleeding, and had no history of abdominal surgery or trauma. On examination, the spleen edge was palpable 10 cm below the left costal margin, but there was no hepatomegaly or lymphadenopathy. Blood tests showed white blood cells 2·9 × 10⁹/L (normal 3·9–9·0 × 10⁹/L), haemoglobin 140 g/L (135–174 g/L), platelets 35 × 10⁹/L (130–400 × 10⁹/L), serum lactate dehydrogenase (LDH) 25·0 μkat/L (1·7–3·4 μkat/L), and soluble interleukin-2 receptor (sIL-2R) 8780 U/ml (145–519 U/ml). Viral serology was not suggestive of recent infection. A whole body CT showed splenomegaly but no other tumours. An aspiration biopsy sample of the iliac bone showed normocellular marrow. We did skin and transbronchial lung biopsies 4 days after admission to look for subclinical lymphomatous lesions. Immediately after bronchoscopy the patient started coughing, then developed left shoulder and upper abdominal pain, and 2 h later became haemodynamically unstable, with a sharp fall in haemoglobin to 81 g/L. A repeat CT showed rupture of the spleen with subcapsular haematoma and haemoperitoneum in the left subphrenic and perihepatic areas (fi gure). At emergency total splenectomy we found about 3 L of blood in the peritoneal cavity. The resected spleen weighed 1070 g and measured 17 × 13 × 6 cm. Sections showed massive infi ltration and proliferation of untypical lymphocytes with splenic infarcts (fi gure). Immunohistochemistry indicated non-Hodgkin’s lymphoma characterised by diff use large B cells, which was confi rmed by skin and lung biopsies (appendix). The patient recovered well and we started him on post-splenectomy vaccination and prophylactic antibiotics and chemotherapy, consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. At follow-up 2 months later serum LDH and sIL-2R had returned to normal and he had no evidence of infection or recurrence of lymphoma.Non-traumatic splenic rupture is rare but can be life-threatening. It usually occurs in an abnormal spleen; causes can be local (splenic thrombosis, pancreatitis), infectious (malaria, bacterial endocarditis, infectious mononucleosis), metabolic (amyloidosis, Gaucher’s disease), and haematological (leukaemia, lymphoma).

We have shown that vitamin E inhibited the apoptosis, DNA modification and cancer induced by iron-mediated peroxidation in the Wistar rat kidney. To further elucidate the effects of vitamin E, we examined the levels of apoptosis and 8-hydroxydeoxyguanosine (8-OHdG) in vitamin E-deficient, -normal (control) and -supplemented rats after a single intraperitoneal injection of ferric nitrilotriacetate (Fe-NTA). Three-week-old male Wistar rats were divided into three groups and maintained on a vitamin E-deficient, -normal or -supplemented diet for 6 weeks. At the end of the 6-week feeding period, the animals were injected intraperitoneally with Fe-NTA or saline. The vitamin E-deficient rats injected with Fe-NTA 3 or 8 mg Fe per kg body weight died within 3.5 h, whereas the vitamin E-normal and -supplemented animals all survived ( n =6 each). In other rats maintained on the above vitamin E diets ( n =13 each), the levels of apoptosis shown by the TUNEL method and 8-OHdG formation shown by immunohistochemistry and an HPLC–ECD method were defined in renal tissues after an intraperitoneal injection of Fe-NTA, 8 mg Fe per kg body weight. The results showed that the generation of both 8-OHdG and apoptosis were definitely inhibited in the vitamin E-supplemented animals, whereas little inhibition was seen in the vitamin E-normal animals. However, the lack of vitamin E induced death by iron-induced oxidative stress with remarkable proximal tubular necrosis and hemolysis.

The copper and iron status in the liver of non-tumor bearing Long-Evans Cinnamon (LEC) rats (average age 17 months) was investigated. A direct quantitation of loosely-bound copper and iron was also investigated by using a chelating agent, nitrilotriacetic acid (NTA-chelatable free copper and iron). Besides the total copper and iron contents, the level of NTA-chelatable free copper was also higher in LEC rats than in LEA rats (P0.05). But for the free iron level there was no significant difference between the two rat groups (P0.05). The formation of thiobarbituric acid-reactive substances was higher in LEC rats than in LEA rats (P0.01). The 4-hydroxy-2-nonenal (HNE)-modified proteins were also clearly demonstrated in LEC rat liver. The copper and iron which produced the most important effect in the process of oxidative damage in LEC rats could not be distinguished. Even though free copper, which could induce free radical injuries, was increased in LEC rats, neither tumor-induction nor preneoplastic lesions in the experimental LEC rats were observed. Therefore it is speculated that the elevation of a free iron is another important factor. Copper and iron, both important transition metals in the body, may participate in the induction of DNA damage and oncogenesis.

A Peutz-Jeghers polyp (PJP) is a hamartomatous lesion characterized by arborescent smooth muscle bundles covered with mucosa native to the site of involvement. PJPs in the small intestine may represent misplacement of non-neoplastic epithelium into the submucosa, muscularis propria and subserosa. Although epithelial misplacement in PJPs is a well-documented phenomenon, pseudoinvasion even into the vascular space in PJPs has not previously been reported. We report a case of a 22-year-old Japanese woman with a solitary PJP in the ileum. The ileal PJP in this patient showed epithelial herniation even into the vascular space. All the herniated epithelium, including the epithelial components invaginated into the vascular space, demonstrated features of pseudoinvasion, that is, presence of normal small intestinal type mucosa accompanied by the lamina propria, absence of any stromal desmoplastic reaction, and retention of the basal-luminal gradient. Pathologists must be aware of the possibility of vascular pseudoinvasion in small intestinal PJPs to avoid overdiagnosis of carcinoma and resulting unnecessary major surgery.

This report describes a slight difference in the rate of decrease of serum paraquat and diquat concentrations in eight human cases of poisoning by the herbicide PreegloxL (containing paraquatCl2, 5% and diquatBr2, 7%) and the distribution of each in three autopsied cases. There was no variation between the serum concentrations of paraquat and diquat within 24 h after ingestion, but paraquat remained at a slightly higher concentration than diquat after more than 24 h. The decrease of urinary paraquat and diquat concentrations was almost the same during the 24-h determination period. In three autopsied cases, diquat concentrations in the tissues were relatively lower than those of paraquat, except in bile. Paraquat and diquat were unevenly distributed in various tissues and fluids, but the distribution patterns of each in any particular tissues were quite similar. As no difference was observed in the decrease of urinary paraquat and diquat, the much higher concentration of diquat in bile indicates that bile may be one of the effective factors in lowering the concentration of diquat in serum and in tissues of the human body long after ingestion.

Toluene concentrations in 9 brain regions of acutely exposed rats and that in 11 brain regions of a human case who inhaled toluene prior to death are described. After exposure to toluene by inhalation (2000 or 10,000 ppm) for 0.5 h or by oral dosing (400 mg/kg), rats were killed by decapitation 0.5 and 4 h after onset of inhalation and 2 and 10 h after oral ingestion. After each experimental condition the highest range of brain region/blood toluene concentration ratio (BBCR) was in the brain stem regions (2.85-3.22) such as the pons and medulla oblongata, the middle range (1.77-2.12) in the midbrain, thalamus, caudate-putamen, hypothalamus and cerebellum, and the lowest range (1.22-1.64) in the hippocampus and cerebral cortex. These distribution patterns were quite constant. Toluene concentration in various brain regions were unevenly distributed and directly related blood levels. In a human case who had inhaled toluene vapor, the distribution among brain regions was relatively similar to that in rats, the highest concentration ratios being in the corpus callosum (BBCR: 2.66) and the lowest in the hippocampus (BBCR: 1.47).

We report a simple, sensitive, and rapid quantitation of Amitraz in plasma after Extrelut-3 column extraction by gas chromatography with nitrogen-phosphorus detection (GC-NPD). The plasma sample was diluted four-fold with borate buffer (0.01M, pH 11), put into an Extrelut-3 column, left for 15 min, and then eluted with 15 mL of n-hexane. The n-hexane eluate was evaporated under nitrogen gas flow at room temperature. The residue was reconstituted with 0.1 mL of acetone containing nitrazepam as an internal standard. A 2-microL aliquot was injected into a wide-bore capillary column GC-NPD. The detection limit was 0.5 ng/mL and linearity was obtained in the range of 1-200 ng/mL. Amitraz in the buffer at pH 11 remained stable in a freezer for one week at -20 degrees C. The GC-NPD method was found useful in studying the pharmacokinetics of a single dose intravenous administration of Amitraz to a dog.

We have hitherto reported the occurrence of acute and subacute renal proximal tubular necrosis and a subsequent high incidence of renal adenocarcinoma in rats and mice given repeated intraperitoneal injections of ferric nitrilotriacetate (Fe-NTA) or ferric ethylenediamine diacetate (Fe-EDDA). The free radical mechanism appears to play an essential role in tissue damage and carcinogenesis. We therefore tested the effect of vitamin E, a known scavenger of free radicals, to determine if it has a protective effect on Fe-NTA-induced toxicity and carcinogenesis. Vitamin E deficient, sufficient, and supplemented Wistar rats (each group consisted of 25 rats) were used. Fe-NTA (1–5mg Fe/kg body weight) was given intraperitoneally twice a week. All the vitamin E-deficient rats died after repeated injections of Fe-NTA. Four of twenty-five vitamin-supplemented rats and 14 of 20 vitamin E-sufficient rats that survived developed renal tumors (P < 0.01) after 1 year. These results strengthened the idea that iron-dependent free radicals contribute to both the initiation and promotion of carcinogenesis, and vitamin E is definitely preventive to those cancer occurrences where free radicals are involved.

Tonsillectomy is often effective in reducing proteinuria in patients with IgA nephropathy (IgAN), which might otherwise lead to renal failure. Twenty-eight patients with IgAN accompanied by chronic tonsillitis were observed for more than 2 years after tonsillectomy and studied clinicopathologically. Tonsillectomy was effective in 17 patients (effective group), but not effective in 11 (noneffective group). Many patients in the effective group showed mild proteinuria, whereas proteinuria of 1 g/24 h or higher was found in a few cases. In comparison with the noneffective group, the levels of serum IgA, polymeric IgA and circulating immune complex (CIC) in the effective group were significantly higher prior to tonsillectomy. Histopathologically, there was only a slight increase in mesangial cells and matrixes in the effective group compared with the noneffective group, and global glomerular sclerosis, small glomerular crescents and interstitial scarring were seldom found. Rupture of the glomerular basement membrane (GBM) occurred more frequently in the noneffective than in the effective group. In a study of IgA subclasses in the mesangial area of the glomerulus, IgA1 was predominantly stained in the effective group.

A rapid, simple method based on second-derivative spectroscopy of the simultaneous analysis of paraquat and diquat in serum and urine is described. Paraquat and diquat in serum were deproteinized with sulfosalicylic acid, and those in urine were reduced with NaOH-dithionite solution. A qualitative and quantitative analysis of reduced paraquat and diquat was made at the amplitude peaks of 396-403 nm and 454-464 nm in the second-derivative spectra, respectively. The entire procedure was completed within about 10 minutes for a serum sample and within about 5 minutes for a urine sample. Application of the proposed method on a poisoned patient is also reported.

I A simple, sensitive, and rapid quantitative method for Dip- terex in serum is described. A SepPak Cle cartridge for the extraction and gas chromatography with flame thermionlc detection for determination are used. The detection limit is 2.5 ng/mL, and linearity is obtained in the range 5-500 ng/mL.