Pulmonary tumor thrombotic microangiopathy during good response to immuno-chemotherapy for advanced non-small cell lung cancer: a case report.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy is a rapidly progressive and fatal disease in which tumor cells embolize to the pulmonary microvasculature. This condition is characterized by severe dyspnea and right heart failure. Although pulmonary tumor thrombotic microangiopathy typically occurs in patients with untreated and/or advanced cancer, its occurrence in patients who are responding well to medical therapy is poorly documented. CASE PRESENTATION: A 68-year-old Japanese woman who had received four cycles of immuno-chemotherapy (pembrolizumab, carboplatin, and pemetrexed) followed by three cycles of maintenance therapy (pembrolizumab and pemetrexed) for advanced non-small cell lung cancer and had achieved a partial response with a stable clinical course was admitted to the emergency ward because of worsening breathlessness and general fatigue for 1 week. Chest computed tomography showed no evidence of tumor progression or any new lung lesion. Two-dimensional transthoracic echocardiography demonstrated right atrial and ventricular dilatation, tricuspid regurgitation, and a high trans-tricuspid pressure gradient of 65 mmHg. Despite her percutaneous oxygen saturation being 96% on room air at the time of admission, it worsened rapidly; the patient requiring 8 L/min of oxygen within 4 h. Repeat computed tomography with contrast medium revealed no evidence of pulmonary embolism. The patient developed progressive respiratory failure that was unresponsive to optimal cardio-pulmonary supportive therapy. An autopsy revealed tumorous clusters in pre-capillary lung vessels, whereas the primary lesion had shrunk to the point of almost complete resolution. CONCLUSION: Pulmonary tumor thrombotic microangiopathy occurs not only in patients with advanced and/or uncontrolled cancer but also in those whose primary lesion seems to have been well controlled by medical treatment.

Alport syndrome: A case study of chronic type A aortic dissection.

A 39-year-old woman with a history of Alport syndrome was admitted to our hospital for heart failure due to severe aortic regurgitation. Computed tomography revealed a chronic type A aortic dissection that required valve-sparing aortic root replacement. The pathological examination demonstrated that elastic fibers in the tunica media of the aortic wall are torn and severely disorganized. Immunostaining showed fragmented alpha 5 chains, indicating Alport syndrome. These findings imply Alport syndrome may have connective tissue vulnerability, rendering patients susceptible to the development of aortic disease at a young age.

Severe Hepatitis-associated Aplastic Anemia Following COVID-19 mRNA Vaccination.

We herein report a case of hepatitis-associated aplastic anemia (HAAA) that occurred after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. In this patient, progressive pancytopenia observed two months after acute hepatitis following the second dose of the SARS-CoV-2 vaccine indicated the development of HAAA. Although some reports have suggested that SARS-CoV-2 vaccination may be involved in the development of autoimmune diseases, no cases of HAAA developing after SARS-CoV-2 vaccination have been reported. SARS-CoV-2 vaccination in children has only started relatively recently, so the range of side effects in children has not yet been thoroughly described. Therefore, we need to strengthen surveillance for symptoms of children who are vaccinated.

Bulky cardiac metastasis of intracranial solitary fibrous tumor/hemangiopericytoma: Delayed metastasis after cranial tumor resection.

We report a case of bulky cardiac metastasis of intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC). A 72-year-old woman developed a chief complaint of chest pain. Contrast-enhanced computed tomography revealed multiple enhanced masses in the heart, retroperitoneum, and femur. Initially, multiple metastases of cardiac primary angiosarcoma were suspected because the cardiac mass was the largest. However, it was diagnosed as SFT/HPC on the basis of biopsy and immunostaining for the retroperitoneal lesion. She had a history of resected brain tumor surgery for a meningioma 11 years earlier, and pathological reconfirmation revealed this was not a meningioma but rather a SFT/HPC. Thus, we found that the enhanced masses were extracranial metastases of an intracranial primary SFT/HPC. She died approximately 3 years after the onset of chest pain. Autopsy confirmed metastasis in the retroperitoneum, liver, lung, mesentery, skeletal muscle, and bone in addition to the heart. SFT/HPC has been reported to easily recur locally and to show systemic metastasis over the long term. Given that SFT/HPC has been recognized as a subtype of meningioma, the differential diagnosis for patients with a history of intracranial tumors, such as meningioma, should include SFT/HPC.

Consideration concerning similarities and differences between ANCA-associated vasculitis and IgG-4-related diseases: case series and review of literature.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and immunoglobulin G4-related diseases (IgG4-RD) are regarded as entirely different disease types with different etiological mechanisms. However, we experienced two cases that had clinical features of both AAV and IgG4-RD. The first case is an 81-year-old woman who showed periaortitis and retroperitoneal fibrosis and periarteritis with elevation of myeloperoxidase-anti-neutrophil cytoplasmic antibody and IgG4 levels. The second case is a 63-year-old woman who had dura mater, ear, nose, lung, and kidney involvement with serum negative for ANCA and elevated IgG4. Renal biopsy revealed tubulointerstitial nephritis involving IgG4+ plasma cells (IgG4+/IgG+ cell ratio of ≥ 40%). On the other hand, lung biopsy showed features of granulomatosis with polyangiitis (GPA). These two cases suggested that AAV and IgG4-RD might overlap. To investigate the similarities and differences between AAV and IgG4-RD, we retrospectively analyzed 13 cases of typical GPA, a subtype of AAV, and 13 cases of typical IgG4-RD at our hospital for comparison of clinical features and found some differences that can be useful in the differential diagnosis between the two diseases. Although AAV and IgG4-RD are distinguishable based on characteristic findings in many cases, the diagnosis can be unclear in rare cases, in which clinicians should consider possible coexistence of AAV and IgG4-RD when performing further workup. Here, we discuss the similarities and differences between AAV and IgG4-RD on the basis of our results and past literature.

Volumetric analysis of a rhabdoid meningioma during preoperative follow-up. A case report.

The authors describe a case of rhabdoid meningioma (RM) in a 17-year-old boy that was determined by measuring the tumor volume during preoperative follow-up. The volume of the tumor located in the left occipital lobe, was measured every 1-5 months, using an image analysis software. The tumor volume doubling time (Td) ranged from 1.0 to 4.9 years in the first 11 months, but became 0.3 years in the last two months. The tumor grew rapidly in the last two months at which time surgery was performed. Pathological examination of the surgical specimen showed that the tumor contained rhabdoid cells (RCs). RCs were heterogeneously distributed in the tumor admixed with spindle-shaped cells. The areas where RCs were predominant had malignant histological features, with necrosis and high proliferation indices, whereas the areas with few RCs lacked the malignant features. The tumor grew slowly in the initial phase, possibly because components with low proliferation rates occupied most of the tumor. The tumor began to grow rapidly when the malignant component containing abundant RCs became predominant. To the authors' knowledge, this is the first report monitoring the volumetric change of RM periodically. Our investigation indicated that volumetric analysis is useful to decide surgical intervention of the meningiomas with potential malignancy.

Pseudo-Gaucher cell proliferation associated with myelodysplastic syndrome.

We report an extremely rare case of pseudo-Gaucher cell proliferation with myelodysplastic syndrome (MDS). A 77-year old Japanese man was referred to our hospital with splenomegaly and thrombocytopenia, and subsequent bone marrow aspiration revealed infiltrates of foamy vacuolated macrophages without any evidence of other morphologic abnormalities. A karyotype analysis showed the presence of 46,XY,del(20)(q11) in 20 of 20 examined bone marrow cells. We performed a splenectomy, and the resulting pathologic findings revealed massive infiltration of foamy vacuolated macrophages, which were morphologically compatible with Gaucher cells. The activities of beta-glucosidase and acid sphingomyelinase were within normal ranges; therefore, the foamy vacuolated macrophages were considered pseudo-Gaucher cells. A diagnosis of MDS, subclassified as refractory anemia, was then made according to World Health Organization classification guidelines. Pseudo-Gaucher cell proliferation and infiltration might therefore be observed in other patients presenting with MDS.

Xanthogranulomatous cholecystitis expressing high levels of DUPAN-II.

We report a case of xanthogranulomatous cholecystitis (XGC) showing high levels of serum DUPAN-II in a 65-year-old woman. Preoperative radiologic examination showed no abnormal findings except in the gallbladder. Endoscopic ultrasonography was effective for differentiating chronic cholecystitis from gallbladder cancer before the operation. Cholecystectomy was performed by laparotomy, and the diagnosis of XGC was confirmed intraoperatively by examining a frozen section. Histologically, no cancer lesion was observed in the gallbladder, while immunochemical reactivity to DUPAN-II was demonstrated in the brush-border area of the epithelium and in histiocytes in the gallbladder. The half-life of serum DUPAN-II in our patient after cholecystectomy was approximately 1 month, and finally dropped to within the normal range after cholecystectomy.

A case of ganglioneuroma in which 131I-6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol scintigraphy showed high uptake in the adrenal gland leading to a misdiagnosis.

We experienced a case in which 131I-6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol (131I-adosterol) scintigraphy showed high uptake in the right adrenal gland. We diagnosed functional cortical adenoma because of the finding of 131I-adosterol scintigraphy. However, no positive findings for the existence of cortical adenoma were obtained in other examinations and we performed right adrenalectomy. Unexpectedly, pathological finding showed the right adrenal gland was occupied with a large ganglioneuroma. This is an instructive case in which 131I-adosterol scintigraphy showed abnormal high uptake in the adrenal gland, in spite of the fact that the adrenal gland was occupied by a tumor derived from adrenal medulla.

Metastasis to the orbit from transitional cell carcinoma of the bladder.

PURPOSE: To demonstrate the pathological features of the extremely rare metastatic transitional cell carcinoma (TCC) from the bladder to the orbit, and to review the literature on metastatic TCC to the orbit. METHODS: A 74-year-old man experienced 2 weeks of red eye, proptosis, diplopia, pain, and visual loss in the right eye. Three years previous to the current presentation, the patient had undergone a transurethral resection for superficial and moderately differentiated TCC of the bladder. A transseptal anterior orbitotomy was performed. RESULTS: Histopathological examination of the orbital lesion revealed nests of carcinomatous cells. Atypical pleomorphic cells with vacuolated cytoplasm were evident. The cellular morphology of the orbital lesion was identical to that of the primary TCC. There have been 12 previously reported cases of metastases to the orbit from TCC of the bladder, with the time from onset of primary TCC to observation of ocular symptoms ranging from 3 weeks to 11 years. Mean survival after orbital metastasis developed from TCC was 3.0 months. CONCLUSION: This study presents a detailed description of the pathological features of metastatic TCC in the orbit. In cases of orbital metastasis from TCC, patient prognosis is very poor.

Urocortin 1 in colonic mucosa in patients with ulcerative colitis.

Ulcerative colitis (UC) is characterized by a long-standing chronic inflammation of the bowel with intermittent periods of exacerbation and remission. Its acute exacerbation appears to be related to various stresses. Urocortin 1 (Ucn1) may play important roles in integrated local responses to stress. We therefore examined local production of Ucn1 in patients with UC by immunohistochemistry and mRNA in situ hybridization. Ucn1 immunoreactivity was predominantly detected in lamina propria plasma cells and enterochromaffin cells. In UC patients without glucocorticoid treatment, Ucn1-positive cells and plasma cells increased in proportion to the severity of inflammation (P < 0.0001). Ucn1-positive cells significantly increased in UC patients with advanced inflammatory grades, compared with a control group (P < 0.0001) and nonspecific colitis group (P < 0.0001). In glucocorticoid-treated patients, Ucn1-positive cells were significantly lower in number, compared with the nonglucocorticoid-treated group. Ucn1 mRNA was expressed in lamina propria plasma cells, and both corticotropin-releasing factor(1) and corticotropin-releasing factor(2(a)) mRNAs were also partially coexpressed in these cells and macrophages. The present study showed that Ucn1-positive cells were correlated with the severity of inflammation in colonic mucosa with UC, and glucocorticoid treatment decreased these cells. Ucn1 therefore may act as a possible local immune-inflammatory mediator in UC.

Expression of progastrin-releasing peptide and gastrin-releasing peptide receptor mRNA transcripts in tumor cells of patients with small cell lung cancer.

PURPOSE: Small cell lung cancer (SCLC) is a rapidly growing neoplasm accounting for approximately 20% of patients with lung cancer. Progastrin-releasing peptide (proGRP) is produced in about two-thirds of SCLC tumors and is used as a specific marker for SCLC. Although GRP is known to have a variety of biological functions, only limited information is available concerning expression of proGRP mRNA and protein, and that of the receptor for GRP (GRPR) in SCLC tumors. METHODS: In individuals with SCLC, the levels of serum proGRP(31-98) were measured by enzyme-linked immunosorbent assay. Expression of proGRP as well as GRPR mRNA in SCLC tumor tissues was investigated by reverse transcription-nested polymerase chain reaction (PCR) amplification. The proportions of alternatively spliced proGRP mRNA transcripts were analyzed in proGRP-producing tumors by nested and competitive PCR amplification. Finally, production of proGRP protein in SCLC tumor was evaluated by using immunohistochemical staining with a polyclonal human anti-proGRP antibody. RESULTS: ProGRP mRNA transcripts could be detected only in tumor tissues recovered from individuals with high serum proGRP levels. The proportions of mRNA subtypes in each case were nearly the same, revealing type I of 55.4+/-7.6%, type II with 21-b deletion of 1.8+/-3.6%, and type III with 19-b deletion of 42.8+/-4.3%, respectively. ProGRP protein production was demonstrated in tumor tissues exclusively from individuals exhibiting high serum proGRP levels. In contrast, GRPR mRNA transcripts were detectable in cancer cells from two of five proGRP-expressing tumor tissues. CONCLUSIONS: ProGRP mRNA expression is closely related with the synthesis of proGRP protein which is eventually released into the blood. It is suggested GRP may function as an autocrine growth factor for cancer cells in a subgroup of SCLC patients through, at least in part, upregulation of GRPR expression.

Association between an increased surface area of peritoneal microvessels and a high peritoneal solute transport rate.

OBJECTIVE: The peritoneal solute transport rate (PSTR) often increases, especially for small solutes, during long-term peritoneal dialysis (PD) treatment. Although the mechanism by which PSTR increases in PD patients is not known, it is likely that an increased PSTR reflects an increased surface area of the peritoneal capillary and post-capillary venules (microvessels), but this has not previously been investigated. The aim of this study was to clarify the relationship between PSTR and peritoneal microvessel alterations in biopsy specimens of peritoneum obtained from PD patients after various times on PD, and the possible contribution of the duration of PD in relation to these alterations. DESIGN: Tissue from the parietal peritoneum was obtained from 22 PD patients (age 48.5 +/- 9.0 years, duration of PD 66.3 +/- 46.6 months, incidence of peritonitis 0.3/patient-year). The patients were subdivided into three groups according to duration of PD: zero months (group 0, n = 4), less than 60 months (group I, n = 7), and more than 60 months (group II; n = 11). METHODS: For each specimen, the relative microvessel area (RVA) calculated as total area of microvessels/total area of peritoneal field, and the relative microvessel number (RVN), calculated as number of microvessels/total area of peritoneal field, were determined. The ratio RVA/RVN was used to assess the average area of microvessels. The PSTR was evaluated for creatinine, glucose, beta2-microglobulin, and albumin using the peritoneal equilibration test. RESULTS: The dialysate-to-plasma concentration ratio (D/P) for creatinine showed a significant positive correlation with both RVA (rho = 0.77, p < 0.001) and RVA/RVN (rho = 0.51, p = 0.01), but not with RVN. The D/P for beta2-microglobulin correlated with RVA (rho = 0.51, p = 0.015) but not with RVN or RVA/RVN. No differences were found between the three groups in the values for RVN, whereas there was an apparent significant increase in RVA with time on PD (p < 0.001 for group 0 vs both groups I and II). Furthermore, in high transporters, RVA tended to be higher in group II than in group I. CONCLUSIONS: The present study demonstrates for the first time that an increased peritoneal solute transport rate (for both creatinine and beta2-microglobulin) is associated with an increased surface area of peritoneal microvessels, especially in patients on long-term PD treatment. This indicates that increased vascularization and/or dilatation of peritoneal microvessels may play a key role in the development of a high PSTR.

Diagnosis of Tis/T1 breast cancer extent by multislice helical CT: a novel classification of tumor distribution.

PURPOSE: To evaluate the clinical usefulness of multislice helical CT (MSCT) for assessing breast cancer extent. MATERIALS AND METHODS: MSCT was performed in 70 patients with Tis/T1 breast cancer [12 ductal carcinoma in situ (DCIS) and 58 invasive carcinoma]. The distribution pattern of contrast enhancement (CE) was classified into five categories: solitary lesion (localized area of CE), grouped lesion (satellite: localized CE with linear and/or spotty enhancement; crowded: clustered spotty enhancement), separated lesion (multifocal foci of CE), mixed lesion (grouped lesion with multifocal foci), and diffuse lesion (diffuse CE). RESULTS: Solitary lesion was seen in five cases of DCIS, 27 invasive carcinomas without intraductal spread (IDS), six invasive carcinomas with IDS, and one multicentric cancer. Grouped lesion was seen in six DCIS and 15 invasive carcinomas with IDS. Separated lesion was seen in one case of invasive carcinoma and fibroadenoma, and three multifocal/multicentric cancers. Mixed lesion was seen in two multicentric cancers. Diffuse lesion was seen in one case of DCIS and three invasive carcinomas. The coincident rate between MSCT pattern and histologic distribution was 85.7% (60/70). In solitary and grouped lesions, accuracy for the detection of tumor extent with a deviation of less than 2 cm in length was 91.7% (55/60). CONCLUSION: MSCT is extremely accurate in the diagnosis of IDS and the multicentricity of breast cancer.

Histologic breast cancer extent after neoadjuvant chemotherapy: comparison with multidetector-row CT and dynamic MRI.

PURPOSE: To evaluate the efficacy of dynamic multidetector-row CT (MDCT) in assessing residual cancer extent after neoadjuvant chemotherapy (NAC), and to compare MDCT results with those derived from dynamic three-dimensional MRI using the volumetric interpolated breath-hold examination (VIBE) sequence. MATERIALS AND METHODS: MDCT before and after NAC was performed in 19 consecutive patients with breast cancer. MRI was also performed before surgery. The early phase of MDCT and MRI was started 60 sec after commencing contrast injection. The late phase was started at a 4-min delay from the injection. The injection rate was 3 mL/sec. The distribution pattern of contrast enhancement (CE) by CT before NAC was classified into two groups: replaced lesion (diffuse CE in whole quadrants) and non-replaced lesion (localized CE). RESULTS: Pathological complete response (pCR) was obtained in one case. In replaced lesions, accuracy for the detection of tumor extent with a deviation of less than 2 cm in length was 0% (0/7) with early-phase CT/MRI and 100% (7/7) with late-phase CT/MRI. In non-replaced lesions, accuracy was 55% (6/11) with early-phase CT/MRI and 82% (9/11) with late-phase CT/MRI. One case of ductal carcinoma in situ (DCIS) could be detected only with late phase MRI. CONCLUSION: Late-phase images obtained by MDCT and MRI may be accurate in the diagnosis of residual cancer extent after NAC. The tumor distribution determined by MDCT before NAC is thought to be useful in the evaluation of shrinkage pattern following NAC.

[Bilateral pyeloureteritis cystica: a case report].

We report here a case of bilateral pyeloureteritis cystica. A 67-year-old woman was admitted to our hospital with asymptomatic macrohematuria in September 1999. Drip infusion pyelography and enhanced computed tomography demonstrated multiple small, round filling defects in both renal pelvises and ureters. Ureteroscopy and cold punch biopsy were performed, and histological examination revealed pyeloureteritis cystica. This patient was not given adjuvant therapy but was carefully followed up for 3 years and 6 months postoperatively.

[Carcinoma of urachus: report of 15 cases and review of literature--is total cystectomy the treatment of choice for urachal carcinoma?].

PURPOSE: This study was undertaken to determine the most appropriate type of operation for the improvement of the radical cure rate and QOL of patients with urachal cancer. We assessed the association between the stage, type of operation, and prognosis of cases we experienced and those reported in Japan. PATIENTS AND METHOD: The subjects included 15 cases of urachal cancer we have experienced in the past 14 years. While clarifying the clinical patterns of these cases, the association between stage, type of operation, and prognosis was studied. Of the cases of urachal cancer reported in Japan in the recent 20 years, 75 cases in which the stage, type of operation, and prognosis were documented were selected, and the association between the stage and outcome in each type of operation was studied. RESULTS: In regard to stage, all the cases were rated as more than IIIA. As for prognosis, 9 cases (60%) are alive without cancer at the present time with a mean survival time of 7 years. Of the above patients, 3 underwent cystectomy and 6 underwent en bloc segmental resection (herein after referred to en bloc). Recurrence or cancer death was experienced in 5 patients, 2 of which were classified as stage IIIA and 3 as IIID. Of these patients, one underwent en bloc, 3 partial resection of the bladder, and one underwent exploratory laparotomy. As far as our study of the cases reported in Japan is concerned, the prognosis of the cases having undergone only partial resection of the bladder was poor, while of the cases having undergone en bloc or total cystectomy 88-100% were alive without cancer for more than 2 years if their stage was classified as IIIA or below. On the other hand, prognosis was very poor whatever the type of operation in the cases whose cancer was stage IIIC or above. CONCLUSIONS: It appears that the en bloc is most appropriate as the type of operation for the cases of urachal cancer and that the application of total cystectomy is limited to some cases. In performing the en bloc, an extensive resection of the peritoneum, resection of the posterior sheath of the rectus muscle of the abdomen, and dissection of the intrapelvic lymph nodes in addition to the conventional types of operation should be carried out positively.