Immunohistochemical Analysis of Toll-Like Receptors, MyD88, and TRIF in Human Papillary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma.

PURPOSE: We hypothesized that innate immune response pathways might be involved in thyroid carcinogenesis. To investigate this hypothesis, we aimed at analyzing the expression of several receptors and molecules in the innate immune system in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) tissues. METHODS: Of the surgically resected specimens, 11 ATC tissues, 25 PTC tissues, and 8 nodular hyperplasia (NH) tissues were selected and examined for the expression of toll-like receptor (TLR) 2, TLR3, TLR4, TLR5, TLR7, TLR9, the myeloid differentiation primary response gene 88 (MyD88), and toll-interleukin-1 receptor domain-containing adaptor inducing INF-ß (TRIF) by immunohistochemistry (IHC). RESULTS: Several TLRs were expressed in each tissue. TLR3 was strongly expressed in all tissues. In contrast, TLR4 was not detected in any tissues. While TLR5 was moderately expressed in NH but significantly reduced in PTC and ATC, TLR9 was absent in NH tissue but moderately expressed in both PTC and ATC. On MyD88 expression, no significant difference was found between PTC and ATC. TRIF was significantly upregulated in PTC and ATC compared to NH. Surprisingly, PTC and ATC tissues exhibited similar expression patterns of TLRs, MyD88, and TRIF. CONCLUSION: These data suggest the involvement of the innate immune system in both PTC and ATC. Specifically, TLR3-mediated TRIF activation was confirmed in PTC and ATC. This provides new insight into thyroid carcinogenesis.

Elective lung resection after treatment for COVID-19 pneumonia.

A 65-year-old man with coronavirus disease 2019 (COVID-19) was admitted to our hospital. Computed tomography detected bilateral pneumonia with a lung nodule suspicious for lung cancer. Lobectomy was performed 3 months after the treatment for COVID-19 without any complications. The surgical specimen revealed fibrosis below the pleura with a small collection of lymphocytes and intravascular hemorrhagic thrombosis, and no residual RNA was detected. This is the first report describing a surgical specimen after recovery from COVID-19 pneumonia, and suggests that elective thoracic surgery can be performed safely, depending on the patient's respiratory function, without infectious risk.

Successful treatment of advanced pancreatic leiomyosarcoma treated with gemcitabine plus nab-paclitaxel: a case report and literature review.

Pancreatic leiomyosarcoma (PLMS) is an extremely rare tumor that accounts for 0.1% of pancreatic malignancies, and its chemotherapy has yet to be established. Generally, soft-tissue sarcoma chemotherapy is standard treatment with doxorubicin (DXR) alone. However, the effectiveness of gemcitabine (GEM) plus docetaxel (DOC) has been shown in uterine leiomyoma. In contrast, the GEM plus nab-paclitaxel (PTX) regimen has been established as first-line chemotherapy for unresectable pancreatic cancer. For this study, we selected the GEM plus nab-PTX regimen for patients with PLMS, achieving success in approximately 10 months. From a search on PubMed, we found only 12 cases of PLMS (including this case) that underwent chemotherapy. Our case is the first reported patient to have survived more than 2 years with chemotherapy alone. In a nude mouse model, the GEM plus DOC regimen was shown to significantly decrease tumor size when compared with DXR in leiomyosarcoma, and the GEM plus nab-PTX regimen was reported to significantly reduce necrosis when compared with DXR alone, GEM alone, DOC alone, nab-PTX alone and GEM plus DOC in soft-tissue sarcoma. GEM plus nab-PTX therapy might therefore be the first choice for soft-tissue sarcoma and leiomyosarcoma. This is the first reported case of PLMS treated with GEM plus nab-PTX.

Invasive hepatic mucormycosis: A case report and review of the literature.

Mucormycosis generally develops under immunocompromised conditions, including hematological malignancies and solid organ or hematopoietic stem cell transplantation. Although mucormycosis usually affects the lungs and paranasal sinuses, sporadic cases of invasive mucormycosis of the liver have been reported. We hereby report a patient with myelofibrosis who developed hepatic mucormycosis diagnosed by post-mortem examination. An extensive literature review identified 13 reported cases of hepatic mucormycosis, including ours, without lung involvement. Most of the underlying diseases or conditions were hematological malignancies and solid organ transplantation. Three cases had splenic lesions and four had gastrointestinal lesions, suggesting the possibility of translocation to the liver and/or spleen from the gastrointestinal tracts. Hepatic mucormycosis should be recognized as one of the presentations of invasive mucormycosis, especially when hepatic nodules are found in immunocompromised patients such as those with hematological malignancy or recipients of solid organ transplantation.

Giant thymoma successfully resected via median sternotomy and anterolateral thoracotomy: a case report.

BACKGROUND: Some patients with thymoma present with a very large mass in the thoracic cavity. Although the most effective treatment for thymoma is surgical resection, it is difficult to perform because of the size of the tumor and the infiltration of tumor into the surrounding organs and vessels. We report a patient with a giant thymoma that was completely resected via a median sternotomy and left anterolateral thoracotomy. CASE PRESENTATION: A 63-year-old woman presented with a mass in the left thoracic cavity that was incidentally found on a chest X-ray. Chest computed tomography revealed a giant mass (16 × 10 cm) touching the chest wall and diaphragm and pressed against the heart and left upper pulmonary lobe. Complete resection was performed via a median sternotomy and left anterolateral thoracotomy. The tumor was histologically diagnosed as a WHO type B2 thymoma, Masaoka stage II. CONCLUSIONS: Giant thymomas tend to grow expansively without invasion into surrounding organs and vessels. Surgical resection that employs an adequate approach must be considered, regardless of the size of the tumor.

Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis) with atypical encephalitis and painful testitis: a case report.

BACKGROUND: Kikuchi-Fujimoto disease is a self-limited clinicopathologic entity that is increasingly recognized worldwide. Kikuchi-Fujimoto disease is characterized by cervical lymphadenopathy occurring in young adults. Neurologic involvement is rare, and testitis directly caused by Kikuchi-Fujimoto disease has not yet been reported. CASE PRESENTATION: A 19-year-old man was brought to our clinic with complaints of fever, headache, fatigue, and left lower quadrant pain that had persisted for 3 weeks. On physical examination, painful cervical lymphadenopathies were observed. Meningitis was suspected based on a cerebrospinal fluid examination, and left-sided orchitis was diagnosed based on findings from magnetic resonance imaging and ultrasonography. However, neither antibiotics nor antiviral drugs were effective in treating the patient's symptoms. On the 20th day of hospitalization, the patient experienced a loss of consciousness, and brain T2-weighted magnetic resonance imaging showed asymmetrical, high-signal intensities in both basal nuclei and the left temporal lobe. Encephalitis was suspected, and the patient was treated with intravenous prednisolone pulse therapy (1 g/day) for 3 days and intravenous immunoglobulin therapy for 5 days. A left cervical lymph node biopsy showed apoptotic necrosis in paracortical and cortical areas with an abundance of macrophages and large lymphoid cells, which had irregular nuclei suggestive of Kikuchi-Fujimoto disease; the pathological findings from a brain biopsy were the same as those of the cervical lymph node biopsy. The encephalitis and cervical lymphadenopathies followed a benign course, as did the testitis. CONCLUSIONS: This is the first report of Kikuchi-Fujimoto disease involving painful testitis and pathologically proven asymmetrical brain regions. Kikuchi-Fujimoto disease should be included in the differential diagnosis when a patient presents with encephalitis, testitis, and fever of unknown origin.

Resection of pulmonary endometriosis using video-assisted thoracoscopic surgery under preoperative CT-guided marking.

Pulmonary endometriosis is a gynecological disorder in which endometrial tissue grows outside of the uterine cavity. Usually, the ectopic implants are located in the pelvis and manifest as dysmenorrhea, chronic pelvic pain, or infertility. Pulmonary endometriosis sometimes occurs in the pleurae and can result in catamenial pneumothorax; however, true pulmonary endometriosis, tissue growing in the lung itself, is rare. We report a 22-year-old patient with pulmonary endometriosis and catamenial hemoptysis. Pulmonary endometriosis was proved histologically and treated successfully by wedge resection using video-assisted thoracoscopic surgery.

Thymoma exhibiting spontaneous regression in size, pleural effusion and serum cytokeratin fragment level: A case report.

A 30-year-old man was admitted to Toho University Omori Medical Center for assessment of right chest pain and fever. Chest computed tomography (CT) revealed an anterior mediastinal tumor sized 11.0×6.0×5.0 cm, with right pleural effusion. The laboratory analysis revealed elevated white blood cell count (11,000/µl), C-reactive protein (4.1 mg/dl) and cytokeratin fragment (CYFRA; 12.7 ng/ml; normal, <2 ng/ml). The level of CYFRA in the pleural effusion was also markedly elevated (143 ng/ml). On the first day after admission (6 days after the initial CT), there was a mild regression on CT (10.0×5.5×4.4 cm; reduction rate, 26.7%), with decrease of the pleural effusion volume. A CT-guided needle biopsy was performed, but the findings were not conclusive, as most of the tissue was necrotic. Seven days later (13 days after the initial CT), a CT revealed further regression (9.5×5.4×4.2 cm; reduction rate, 34.7%) with disappearance of the pleural effusion. The patient was followed up on an outpatient basis. At 35 days after the initial CT, the tumor continued to shrink without treatment (8.0×3.6×3.0 cm; reduction rate, 73.8%) and the serum CYFRA level had decreased to 0.8 ng/ml, although it had not returned to normal levels. At 62 days after the initial CT, the patient underwent surgical resection. The resected specimen was diagnosed as thymoma (World Health Organization type B2; Masaoka classification, stage II), with prominent degeneration and necrosis. One possible cause of the spontaneous regression may be increased internal pressure, probably associated with rapid tumor growth, leading to massive necrosis with resulting chest pain, inflammatory reaction with pleural effusion and subsequent tumor regression. The serum CYFRA level may be a useful marker for the evaluation of the clinical course of thymoma with extensive necrosis.

Investigation of ossification in the posterior longitudinal ligament using micro-focus X-ray CT scanning and histological examination.

BACKGROUND: Ossification in the posterior longitudinal ligament (PLL) correlates with changes of enthesis during the early stages of development, but this issue remains controversial, as little is known regarding the details of this process. The aim of the present study was to elucidate part of the ossification mechanism. Thus, in the present study, we observed and evaluated minute ossifications in the PLL that did not exhibit symptoms of ossification of the posterior longitudinal ligament (OPLL). METHODS: The subjects in the present study were derived from serial autopsy cases from January 2009 to December 2013 at Toho University Omori Medical Center, Japan. Minute ossifications in the PLL from autopsy subjects without any history of OPLL were screened as high-density areas using micro-focus X-ray CT, and the foci were histologically examined. Subsequently, we conducted both micro-focus X-ray CT image analysis and histological examination, and evaluated the correlation between these findings and putative predictive factors reported in previous studies. RESULTS: A total of 103 individuals among the 267 subjects involved in the present study were analyzed within the study period. There were no cases involving OPLL identification prior to death, and no subjects presented with neurological symptoms of myelopathy. The incidence of cases involving high-density areas greater than 0.1 mm(2) in the PLL was 46.6 %, half of which revealed mature bone structures inside this area. Thus, the high-density areas comprised three types: a continuous posterior-annular fibrosus type (23 cases), an isolated posterior-annular fibrosus type (11 cases), and a posterior-vertebral type (29 cases). However, a positive correlation was observed between the proportion of high-density areas, age (Pearson r = 0.265, p < 0.01), and HbA1c (Pearson r = 0.294, p < 0.01). Histological examination confirmed that these high-density areas involved calcification with or without mature bone formation. CONCLUSIONS: We evaluated minute foci of calcification with and without ossification in the PLL from 103 cadavers, generating the following observations: 1. Minute calcification foci greater than 0.1 mm(2) were observed in the PLL of 48 cases (46.6 %), half of which revealed mature bone structures inside this area (23.3 %). 2. The proportion of minute calcification foci observed in the present study was correlated with age and glucose tolerance, suggesting changes in the OPLL in the early stage. 3. Three different mechanisms of ossification were suggested: The two structures developed behind the disc might reflect the elongation of enthesis or rupture of annular fibrosus, while the remaining structure developed behind the vertebral body might reflect a dystrophic calcification-based bony metaplasia sequence.

A case of postoperative hepatic granuloma presumptively caused by surgical staples/clipping materials.

A 66-year-old man with postsigmoidectomy status for colon cancer received laparoscopic partial hepatectomy due to a hepatic mass with employing titanium clips were for a vascular clamp. Histological examination showed liver metastasis from sigmoid colon cancer. Twenty-nine months after the partial hepatectomy, a mass developed on the stump at the hepatic resection. Laparoscopic left lateral segmentectomy was conducted under suspicion of cancer recurrence and an automatic titanium stapling device was used. The macroscopically cut surface of the liver showed a grey-white solid nodule measuring 23 x 20 mm and involving metal clips. The nodule was consistent with granuloma microscopically. Twenty-three months after the segmentectomy, a mass reappeared on the hepatic radial margin and an open left lateral hepatic lobectomy was performed because of its growth tendency. Histopathological examination revealed granuloma similar to the previous instance. Since these nodules formed a granulomatous lesion surrounding metal staples/clips and evidence of caseous necrosis was lacking, granuloma due to surgical staples/clips was suspected. Sporadic case reports of postoperative pulmonary granuloma at the staple line have been published previously, but there are no articles detailing a case involving hepatic granuloma. We present our case as the first report of postoperative staple-line hepatic granuloma.

Gangliocytic paraganglioma: a multi-institutional retrospective study in Japan.

BACKGROUND: Gangliocytic paraganglioma (GP) is an extremely rare benign tumor that commonly arises from the second part of the duodenum. Since GP exhibit neither prominent mitotic activity nor Ki-67 immunoreactivity, this tumor is often misdiagnosed as neuroendocrine tumor (NET) G1 (carcinoid tumor). However, patients with GP may have a better prognosis than patients with NET G1. This fact emphasizes the importance of differentiating GP from NET G1, but few studies have reported the epidemiology and histopathology of GP because of its rarity. To differentiate GP from NET G1 with ease, we conducted a multi-institutional retrospective study analyzing the morphometric and immunohistochemical features of this tumor. METHODS: Since only a limited number of patients with GP could be identified in our institute, we conducted a multi-institutional retrospective study of GP in Japan, which was approved by the Ethics Committee of our medical institute. The obtained tissue sections underwent detailed morphometric and immunohistochemical analyses. Additionally, to differentiate GP from NET G1 with ease, immunohistochemical findings were compared. RESULTS: In our examination of 12 cases of duodenal GP, we found that epithelioid cells of GP exhibited positive reactivity for progesterone receptor and pancreatic polypeptide, whereas tumor cells of NET G1 were completely negative reactivity for both. Additionally, although GP is considered to be an extremely rare NET, we found that four (40.0%) of the ten patients at our institute with duodenal NET G1 actually had GP. CONCLUSIONS: Although GP is regarded as a rare NET, our results suggest that it accounts for a substantial percentage of duodenal NETs. Additionally, confirmation of immunoreactivity for progesterone receptor and pancreatic polypeptide can assist in differentiating GP from NET G1.

Isolated nodular thymic amyloidosis associated with diplopia.

An 85-year-old man presented with diplopia and anterior mediastinal tumor that had enlarged during the preceding 4-year period. Computed tomographic chest imaging showed an irregularly shaped mass comprising two nodules (diameter, 4 cm) with calcification. Suspecting thymoma, we performed video-assisted thoracoscopic thymectomy. The resected specimen showed deposition of homogeneous eosinophilic and hyalinized material around the vessel wall in thymic tissue, and it stained positively for anti-λ antibody, indicating localized AL amyloidosis. There was no other organ dysfunction or symptoms and no evidence of systemic amyloidosis. Diplopia resolved immediately after thymectomy; however, the connection of diplopia with amyloidoma and thymic tissue remains uncertain.

Comparison between the location and the histomorphological/immunohistochemical characteristics of noninvasive neoplasms of the ampulla of Vater.

To determine useful factors when selecting an appropriate procedure for noninvasive ampullary neoplasia, we investigated the relationship between the location and the histomorphological/immunohistochemical characteristics of 56 noninvasive ampullary neoplasms obtained by endoscopic papillectomy (EP). All subjects were classified according to histomorphology and location of neoplasms, and we evaluated the characteristics of each classified group using complementary immunohistochemical procedures. The CK20-positive rates of each location type were also evaluated. Subjects presented with 52 intestinal-type adenomas (low/high grade, 32:20) and 4 noninvasive pancreatobiliary papillary neoplasms (low/high grade, 1:3). Twenty-seven periampullary (peri-AMP)-type tumors and 23 extended-type tumors comprised the intestinal type, and the intra-ampullary (intra-AMP) type was composed of 4 pancreatobiliary and 2 intestinal histomorphological types. The CK20-positive rates of these 3 location types differed significantly (peri-AMP type, 50.6% ± 21.0%; extended type, 35.4% ± 18.6%; intra-AMP type, 6.9% ± 6.3%). The CK20-positive rate for intestinal-type tumors of the intra-AMP location type was lower than that of the peri-AMP location type. Intestinal-type tumors without CDX2 expression included extended and intra-AMP types, which are tumors that may show positive vertical margins when EP is performed. In this study, we found that an understanding of pancreatobiliary-type histology is an important aspect for the investigation of tumors involving the common channel of the ampulla. Furthermore, immunostaining of CDX2 and CK20 provides beneficial information if considering whether to perform an EP.

Interrupted aortic arch with massive saccular collateral aneurysm in an adult.

A 49-year-old man was diagnosed with an interrupted aortic arch (IAA), a massive saccular thoracic collateral aneurysm, ischemic renal insufficiency, and multiple abdominal collateral aneurysms. A bypass from the left subclavian artery to the descending aorta and thoracic collateral aneurysmectomy proceeded simultaneously through a posterolateral thoracotomy. The pressure gradient between upper and lower extremities disappeared and renal function was normalized. Thoracic collateral aneurysmectomy and a simultaneous bypass from the left subclavian artery to the descending aorta with postoperative normalization of ischemic renal insufficiency are extremely rare in adult patients with IAA, and the remaining abdominal collateral aneurysms require careful monitoring.

Remodeling of the pulmonary artery induced by metastatic gastric carcinoma: a histopathological analysis of 51 autopsy cases.

BACKGROUND: Gastric carcinoma remains the second commonest cause of cancer deaths worldwide. Presence of the carcinoma cell in the pulmonary artery is serious condition that might cause remodeling of the pulmonary artery. The present study conducted detailed histopathological analyses to elucidate how gastric carcinoma cells may affect the structure and hemodynamics of pulmonary arteries. METHODS: Remodeling of the pulmonary artery was assessed based on measurements of arterial diameters and stenosis rates from the autopsies, and their correlation were also validated. We additionally calculated 95 percent confidential intervals (CIs) for the rate of stenosis in groups of pulmonary arteries of different caliber zones (under 100, 100 to 300, and over 300 micrometer). The right ventricular thickness was measured and examined whether it correlated with the rate of pulmonary arterial stenosis. RESULTS: A total of 4612 autopsy cases were recorded at our institute, among which 168 had gastric carcinoma. Finally, 51 cases of the gastric carcinoma were employed for the study which had carcinoma cells in the lumen of the pulmonary artery. The mean right ventricular wall thickness of these cases was 3.14 mm. There were significant positive associations between the rates of pulmonary arterial stenosis and right ventricular thickness from pulmonary arteries of diameter under 100, 100 to 300, and over 300 micrometer. In these zones, 31, 31, and 33 cases had rates of pulmonary arterial stenosis that were below the lower limit of the 95 percent CI values, respectively. On the other hand, among cases with significant pulmonary stenosis, 17 of 18 cases with stenosis in the over 300 micrometer zone involved pulmonary arteries of both in the under 100 and 100 to 300 micrometer zones. CONCLUSION: One-third of autopsy with advanced gastric carcinoma had carcinoma cells in lumen of pulmonary artery, but implantation and proliferation may be essential to induce intimal thickening that causes an increasing of pulmonary arterial pressure, because our study revealed a significant positive association between the rate of pulmonary arterial stenosis and right ventricular thickness. In addition, diffuse type gastric carcinoma may be apt to cause the remodeling of the pulmonary artery.

Invasive tracheobronchial aspergillosis in a patient with systemic lupus erythematosus-dermatomyositis overlap syndrome.

A 45-year-old man was referred to our hospital with a 3-month history of dyspnea, polyarthralgia, myalgia and weight loss. He was diagnosed with systemic lupus erythematosus/dermatomyositis overlap syndrome with lung involvement, which presented as organizing pneumonia. However, a bronchoscopic examination revealed the presence of multiple plaque-like white lesions with ulcers on the bronchial membrane, located mainly in the central airway. The pathological specimens obtained from bronchoscopy showed numerous filamentous fungal hyphae that were aggressively invading the bronchial walls, suggesting a diagnosis of invasive tracheobronchial aspergillosis. The present case, along with a review of the literature, demonstrates that invasive tracheobronchial aspergillosis can occur in patients who do not appear to be immunosuppressed. This case of aspergillosis should thus be recognized as an extremely rare presentation of an Aspergillus infection.

How histopathology can contribute to an understanding of defense mechanisms against cryptococci.

Invasive fungal infections, particularly those considered opportunistic, have become a common and significant complication of procedures performed in advanced contemporary medicine. Among such infections, cryptococcosis, which is usually caused by infection with Cryptococcus neoformans and Cryptococcus gattii, is particularly problematic because this fungal infection occurs in immunocompromised and apparently immunocompetent individuals. It has been largely accepted that Cryptococcus species are recognized by cellular receptors and that Th1-type immune responses play an important role in defense mechanisms against the yeast. However, the interaction between the yeast and host tissue varies depending on the characteristics of the yeast and the immune status of the host. To gain a better understanding of the pathophysiology of cryptococcosis, we wish to emphasize the usefulness of histopathological examinations, because it allowed more detailed information of an extremely complex interaction between the causative yeasts and tissue response. In the present review, we describe the pathophysiology of cryptococcosis as largely revealed in our previous histopathological investigations of the experimental infection.

Pathophysiological implication of reversed CT halo sign in invasive pulmonary mucormycosis: a rare case report.

BACKGROUND: It has been accepted that reversed halo sign (RHS) appeared on a computed tomography (CT) image in immunocompromised patients indicates an invasive fungal infection, but its pathophysiology remains obscure as to what this image implies. Therefore, the present report describes detailed radiological and histopathological findings of a case of invasive pulmonary mucormycosis (IPM) presenting RHS with comparison to those from a lesion of discrete nodule caused by invasive pulmonary aspergillosis (IPA), and discusses the pathophysiological implications of this characteristic image. CASE PRESENTATION: RHS had been clinically noted at the time of recovering of bone marrow function of a 64-year-old Japanese man who had chemotherapy for his acute lymphoblastic leukemia. Histological examination of the surgically removed lung revealed a lesion of IPM. This was composed of coagulation necrosis of septa at the center of lesion with preservation of air content which was encompassed outer rim comprising triplet structure; liquefaction, consolidation, and organization from the inner to the outer layer. In addition, Micro-CT examination confirmed reticular structure and monotonous high density at the central coagulation necrosis preserving air content and surrounding consolidation, and organization lesion of the IPM lesion. CONCLUSION: Our investigations suggest that RHS might be understood as a kind of immune reconstitution syndrome and be the initial and prior status of air crescent sign. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3480054198968132.

Ciliated muconodular papillary tumor of the lung: a newly defined low-grade malignant tumor with CT findings reminiscent of adenocarcinoma.

A ciliated muconodular papillary tumor has been reported to be a peripheral low-grade malignant tumor, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation. Although ciliated muconodular papillary tumors have not yet been classified according to the World Health Organization classification, they can pose diagnostic and therapeutic problems. Here we report a resected case of ciliated muconodular papillary tumor with computed tomography findings reminiscent of adenocarcinoma, showing a small irregular nodule adjacent to the intersegment pulmonary vein. There was no uptake of F-18 fluorodeoxyglucose positron emission tomography. The patient underwent surgical resection, and a lobectomy was performed because intraoperative needle biopsy suggested neoplastic proliferation. No EGFR mutations were detected. No recurrence was noted during 24-month follow-up after lobectomy.