Mean computed tomography value to predict spread through air spaces in clinical N0 lung adenocarcinoma.

BACKGROUND: The aim of this study was to assess the ability of radiologic factors such as mean computed tomography (mCT) value, consolidation/tumor ratio (C/T ratio), solid tumor size, and the maximum standardized uptake (SUVmax) value by F-18 fluorodeoxyglucose positron emission tomography to predict the presence of spread through air spaces (STAS) of lung adenocarcinoma. METHODS: A retrospective study was conducted on 118 patients those diagnosed with clinically without lymph node metastasis and having a pathological diagnosis of adenocarcinoma after undergoing surgery. Receiver operating characteristics (ROC) analysis was used to assess the ability to use mCT value, C/T ratio, tumor size, and SUVmax value to predict STAS. Univariate and multiple logistic regression analyses were performed to determine the independent variables for the prediction of STAS. RESULTS: Forty-one lesions (34.7%) were positive for STAS and 77 lesions were negative for STAS. The STAS positive group was strongly associated with a high mCT value, high C/T ratio, large solid tumor size, large tumor size and high SUVmax value. The mCT values were - 324.9 ± 19.3 HU for STAS negative group and - 173.0 ± 26.3 HU for STAS positive group (p < 0.0001). The ROC area under the curve of the mCT value was the highest (0.738), followed by SUVmax value (0.720), C/T ratio (0.665), solid tumor size (0.649). Multiple logistic regression analyses using the preoperatively determined variables revealed that mCT value (p = 0.015) was independent predictive factors of predicting STAS. The maximum sensitivity and specificity were obtained at a cutoff value of - 251.8 HU. CONCLUSIONS: The evaluation of mCT value has a possibility to predict STAS and may potentially contribute to the selection of suitable treatment strategies.

Spontaneous regression of small cell lung cancer associated with Lambert-Eaton Myasthenic Syndrome: Case report.

Spontaneous regression (SR) of cancer is very rare, especially of small cell lung cancer (SCLC). Recently, an association of paraneoplastic neurological syndrome (PNS) has been reported as a cause of SR of cancer, and onconeural antibodies are a possible factor in the SR of cancer associated with PNS. We herein report the first case of SR of SCLC combined with anti-P/Q-type of voltage-gated calcium channel (VGCC) antibody-positive Lambert-Eaton myasthenic syndrome (LEMS), a subtype of PNS. This case report suggests that SCLC may be spontaneously reduced by an autoimmune response induced by VGCC antibodies associated with LEMS. Our finding may help elucidate the mechanisms that inhibit tumor growth and cause the regression of tumors.

Kimura disease forming a human polyomavirus 6-negative parotid gland nodule with prominent squamous metaplasia in a young female: A case report.

A case of an asymptomatic 19-year-old woman with Kimura disease presenting with a nodule in the right parotid gland is presented. She had a medical history of atopic dermatitis and noticed a mass on her right-side neck. Cervical lymphadenopathy was clinically diagnosed. The initial management plan was to observe the lesion, which had enlarged from 1 cm to 2 cm in diameter 6 months later. An excisional biopsy was performed, and the pathology confirmed an eosinophil-containing inflammatory parotid gland lesion with many squamous nests and cysts, mimicking a parotid gland tumor. High serum immunoglobulin E levels, peripheral blood eosinophilia, and pathological and genetic diagnoses confirmed Kimura disease. The lesion tested negative for human polyomavirus 6. No recurrence was observed 15 months after the biopsy. The prognosis of Kimura disease without human polyomavirus 6 infection may be favorable; however, further validation of this hypothesis is required as only 5 or 6 cases of Kimura disease have been evaluated for this viral infection. Proliferative squamous metaplasia occurring in parotid gland lesions of Kimura disease is rare and may complicate the diagnostic imaging and pathological diagnosis.

Predicting the pathological invasiveness of early lung adenocarcinoma prior to surgery using Deauville criteria: reliability and validity.

PURPOSE: This retrospective study aimed to investigate the validity and reliability of FDG-PET/CT visual assessment using Deauville criteria to predict pathological invasiveness of early lung adenocarcinoma prior to surgery. MATERIALS AND METHODS: Between April 2020 and January 2022, 51 patients who underwent surgery for pathological stage 0/I lung adenocarcinoma were enrolled. The pulmonary lesions were divided into two groups according to pathological invasiveness: less invasive (including adenocarcinoma in situ and minimally invasive adenocarcinoma and invasive adenocarcinoma. We compared CT size (total and solid size), SUVmax, and Deauville score between the two groups. Furthermore, we investigated inter-rater and intra-rater agreements regarding the Deauville score. Receiver operating characteristic (ROC) curve analysis was performed to identify the diagnostic performance of each method. RESULTS: Based on pathologic diagnoses, 51 lesions in the 51 patients were divided into 6 less invasive and 45 invasive adenocarcinoma lesions. According to quadratic-weighted Kappa statistics, inter-rater (k = 0.93) and intra-rater (k = 0.97) agreements among all five components of the Deauville score indicated high agreement. There was a statistically significant difference in CT solid size, SUVmax, and Deauville score between the two groups. There were no significant differences between CT solid size and FDG-PET/CT assessments (AUC = 0.93 for Deauville score and SUVmax, AUC = 0.84 for CT solid size). CONCLUSION: FDG-PET/CT visual assessment using the Deauville score could assist in deciding upon minimally invasive surgery for early lung adenocarcinoma.

Cutaneous acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia with proliferation of mature sebocytes: A case report.

Acantholytic dyskeratotic acanthoma is a rare variant of epidermal acanthoma. It has a flat, plaque-like structure and is characterized microscopically by acantholysis and dyskeratosis. Eccrine syringofibroadenomatous hyperplasia is benign and likely reactive. It has recently been considered as a hyperplastic process affecting the eccrine ducts rather than the neoplasm because of its pathological heterogeneity and wide clinical associations. In this article, we present the case of 97-year-old Japanese women with a 10-mm wide, painful acantholytic dyskeratotic acanthoma accompanied by syringofibroadenomatous hyperplasia in the right femoral region. Although syringofibroadenomatous hyperplasia is known to occur as a reactive process with various dermatoses and cutaneous tumors, to date, there have been no reports of cases of acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia. Moreover, this case also includes the unusual finding of an increase in the mature sebocytes in the area of the syringofibroadenomatous hyperplasia.

Merkel cell polyomavirus and Langerhans cell neoplasm.

BACKGROUND: The relationship between various external agents such as pollen, food, and infectious agents and human sensitivity exists and is variable depending upon individual's health conditions. For example, we believe that the pathogenetic potential of the Merkel cell polyomavirus (MCPyV), the resident virus in skin, is variable and depends from the degree of individual's reactivity. MCPyV as well as Epstein-Barr virus, which are normally connected with humans under the form of subclinical infection, are thought to be involved at various degrees in several neoplastic and inflammatory diseases. In this review, we cover two types of Langerhans cell neoplasms, the Langerhans cell sarcoma (LCS) and Langerhans cell histiocytosis (LCH), represented as either neoplastic or inflammatory diseases caused by MCPyV. METHODS: We meta-analyzed both our previous analyses, composed of quantitative PCR for MCPyV-DNA, proteomics, immunohistochemistry which construct IL-17 endocrine model and interleukin-1 (IL-1) activation loop model, and other groups' data. RESULTS: We have shown that there were subgroups associated with the MCPyV as a causal agent in these two different neoplasms. Comparatively, LCS, distinct from the LCH, is a neoplastic lesion (or sarcoma) without presence of inflammatory granuloma frequently observed in the elderly. LCH is a proliferative disease of Langerhans-like abnormal cells which carry mutations of genes involved in the RAS/MAPK signaling pathway. We found that MCPyV may be involved in the development of LCH. CONCLUSION: We hypothesized that a subgroup of LCS developed according the same mechanism involved in Merkel cell carcinoma pathogenesis. We proposed LCH developed from an inflammatory process that was sustained due to gene mutations. We hypothesized that MCPyV infection triggered an IL-1 activation loop that lies beneath the pathogenesis of LCH and propose a new triple-factor model.

Hepatic stellate cells derived from the nestin-positive cells in septum transversum during rat liver development.

Hepatic stellate cells (HSCs) play a principal role in Vitamin A metabolism and are considered the major matrix-producing cell type in the diseased liver. Rat HSCs are identified by immunohistochemistry with myogenic or mesenchymal (desmin, vimentin, and alpha-smooth muscle actin) or neural (e.g., GFAP or neuronal cell adhesion molecule) markers. Embryonic origin of rat HSCs was determined using these markers. Nestin, an intermediate filament protein originally identified in neuronal stem or progenitor cells, is widely used as a stem cell marker, including hepatic stem cells in adult rat livers. Additionally, nestin is reportedly expressed in activated HSCs during liver injury and hepatic regeneration. However, little is known about nestin expression in rat fetal liver HSCs. The present study aimed to clarify nestin-positive HSC expression during rat liver development. At embryonic day (ED) 10.5, nestin expression in mesenchymal cells adjacent to the liver bud was detected by immunohistochemistry. At ED 11.5, nestin-positive cells were also detected in desmin-positive cells appearing and increasing in intensity by ED 16.5. However, nestin-positive cells in the parenchyma decreased by ED 20.5 or later. These findings reveal that the nestin-positive HSCs during rat liver development originate from nestin-positive mesenchymal cells in the septum transversum.

[A case of serous cystic neoplasm of the pancreas with stenosis of the main pancreatic duct].

A 64-year-old woman was accidentally detected to have multiple cystic tumors measuring 30 mm in diameter in the pancreatic head in 2009. The probable diagnosis was a serous cystic neoplasm of the pancreas. However, the tumor had grown to 52 mm in diameter in 4 years, and endoscopic retrograde pancreatography (ERCP) showed stenosis of the main pancreatic duct. We performed subtotal stomach-preserving pancreaticoduodenectomy, and histopathological diagnosis was serous cystadenoma.

Decreased miR-26a expression correlates with the progression of podocyte injury in autoimmune glomerulonephritis.

MicroRNAs contribute to the pathogenesis of certain diseases and may serve as biomarkers. We analyzed glomerular microRNA expression in B6.MRLc1, which serve as a mouse model of autoimmune glomerulonephritis. We found that miR-26a was the most abundantly expressed microRNA in the glomerulus of normal C57BL/6 and that its glomerular expression in B6.MRLc1 was significantly lower than that in C57BL/6. In mouse kidneys, podocytes mainly expressed miR-26a, and glomerular miR-26a expression in B6.MRLc1 mice correlated negatively with the urinary albumin levels and podocyte-specific gene expression. Puromycin-induced injury of immortalized mouse podocytes decreased miR-26a expression, perturbed the actin cytoskeleton, and increased the release of exosomes containing miR-26a. Although miR-26a expression increased with differentiation of immortalized mouse podocytes, silencing miR-26a decreased the expression of genes associated with the podocyte differentiation and formation of the cytoskeleton. In particular, the levels of vimentin and actin significantly decreased. In patients with lupus nephritis and IgA nephropathy, glomerular miR-26a levels were significantly lower than those of healthy controls. In B6.MRLc1 and patients with lupus nephritis, miR-26a levels in urinary exosomes were significantly higher compared with those for the respective healthy control. These data indicate that miR-26a regulates podocyte differentiation and cytoskeletal integrity, and its altered levels in glomerulus and urine may serve as a marker of injured podocytes in autoimmune glomerulonephritis.

Mucinous Cystadenoma in the Upper Lip: Report of Two Cases.

Mucinous cystadenoma of the salivary gland is a very rare disease, and only a few cases have been reported. We report here 2 cases of mucinous cystadenoma in the upper lip. The first case was a 57-year-old man and the second was a 42-year-old woman. The tumors were painless nodules with a smooth-surfaced mucosa, and surgical excisions were performed. Histologically, the tumors were surrounded by a fibrous capsule and were composed of multiple cysts lined with columnar epithelial cells. The tumor cells contain mucous substances that reacted with periodic acid-Schiff base and Alcian blue. Immunohistochemical staining revealed that the tumor cells expressed cytokeratin (AE1/3 and CK7), but their immunoreactivity with MIB-1 (Ki-67) was less than 3%. They had negative immunoreactivity for neuroectoderm markers, S-100 protein, and myoepithelial markers, p63, α-smooth muscle actin, and calponin, except for the accompanying myoepithelial-like cells. No recurrences were noted after surgery at 7 years and 1 year, respectively.

Smear cytology findings of large cell neuroendocrine carcinoma of the uterine cervix.

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a rare tumor. Moreover, there are only three reports to date that have focused on the cytologic findings of cervical LCNEC. We report the case of a 59-year-old Japanese woman with cervical LCNEC combined with small cell carcinoma (SmCC). Cytologic specimens from the uterine cervix demonstrated large cells with coarse chromatin and prominent nucleoli. Frequent mitotic figures were also observed. Curettage of the uterine endometrium revealed an endometrioid adenocarcinoma with squamous differentiation; i.e., an adenoacanthoma. Histologic examination of surgically resected uterine cervical tissue revealed LCNEC with minor foci of SmCC. Neuroendocrine differentiation in LCNEC was confirmed by immunohistochemistry for synaptophysin and CD56. Cytotechnologists or pathologists need to consider a differential diagnosis of LCNEC while examining cervical cytologic specimens; therefore, it is important to correctly identify the cytologic characteristics of this tumor.

Chromophobe renal cell carcinoma with prominent lymph node metastasis and polysomy of chromosome 21: poorly differentiated form or "presarcomatoid" form?

Lymph node metastasis of chromophobe renal cell carcinoma (RCC) is extremely rare. It has been recently reported that sarcomatoid chromophobe RCC frequently show polysomy of chromosomes 1, 2, 6, 10, and 17. In this article, we report an unusual case of chromophobe RCC. A 42-year-old Japanese woman presented with hematuria and complained of inguinal pain 2 months after the initial symptoms. Radical nephrectomy and renal hilar lymphadenectomy were performed. The tumor was 8 cm in greatest diameter; its cut surface was beige in color. Large metastasis to the renal hilar lymph node was identified. Histological examination of the right renal tumor met the criteria of chromophobe RCC. In addition to histological findings of typical chromophobe RCC, small cell foci, comedo-like necrosis, trabecular growth pattern, and sclerosing stroma were observed. However, no sarcomatoid foci were identified anywhere, despite extensive tumor sampling including lymph node lesions. Immunohistochemically, neoplastic cells were positive for E-cadherin and CD117 (c-kit). Ultrastructurally, tumorous cells contained abundant mitochondria and cytoplasmic microvesicles. Fluorescence in situ hybridization showed monosomy of chromosomes 2 and 10 and polysomy of chromosome 21. Finally, we suggest that this tumor may show the poorly differentiated or presarcomatoid form of chromophobe RCC.

Early gastric cancer with widespread duodenal invasion within the mucosa.

We report a rare case of early gastric cancer confined to the mucosal layer with extensive duodenal invasion, curatively removed with distal gastrectomy. An 84-year-old Japanese woman was referred to our hospital with gastric cancer. A barium meal examination and esophagogastroduodenoscopy revealed an irregular nodulated lesion measuring 6.5x5.5 cm in the gastric antrum and an aggregation of small nodules in the duodenal bulb. A biopsy specimen showed well-differentiated adenocarcinoma. The patient underwent distal gastrectomy with partial resection of the duodenal region containing the tumor and regional lymph node dissection, with no complication. Histological examination of the resected tissue confirmed well-differentiated adenocarcinoma limited to the mucosal layer and without lymph node metastasis. The cancer extended into the duodenum as far as 38 mm distant from the pyloric ring, and the resected margins were free of cancer cells. Gastric cancer located adjacent to the pyloric ring thus has the potential for duodenal invasion, even when tumor invasion is confined to the mucosal layer. In such cases, care should be taken during examinations to detect duodenal invasion, and the distal surgical margin must be negative given sufficient duodenal resection.

[Renal cell carcinoma with rhabdoid features and sarcomatoid change: a case report].

In Feb 2009, a-54-year-old female complained of left flank pain and macrohematuria. Computed tomography (CT) demonstrated the left renal tumor. In Mar 2009, she was referred to our hospital. On physical examination a hard mass was found in her left abdomen. CT demonstrated the left renal tumor and tumor thrombus of left renal vein, but we did not detect any remarkable metastasis in other organs. Thus, we performed left radical nephrectomy. The pathologic finding was renal cell carcinoma (RCC) with rhabdoid features and sarcomatoid change. Eight months postoperatively, she is alive without evidence of recurrence and metastasis. RCC with rhabdoid features and sarcomatoid change is rare. We discuss this case, and review the literature.

Signet-ring stromal tumor of the ovary: an immunohistochemical and ultrastructural study with a review of the literature.

Signet-ring stromal tumor is a very rare type of ovarian neoplasm. Only ten cases of this tumor have been reported in the English literature. We report here an additional case of this type of tumor that arose from the left ovary in a 76-year-old woman. By light microscopy, the tumor was composed of small round and oval cells with cytoplasmic vacuolization and a typical signet-ring appearance, focally admixed with fibromatous tissue. Special staining revealed that the vacuoles of the tumor cells contained no lipid, mucoprotein, or glycogen. Interestingly, variously sized hyaline globule-like structures positive for periodic acid-Schiff (PAS) reaction with and without diastase digestion were present in the cytoplasm of tumor cells. Immunohistochemically, the tumor cells variously expressed several markers, including CD56, inhibin-alpha, alpha-smooth muscle actin (alpha-SMA), and progesterone receptor (PR), which have been identified in ovarian sex cord-stromal neoplasms. Ultrastructurally, the hyaline globule-like structures in tumor cells appeared to be lysosomes, and the vacuoles in the cells appeared to have resulted from pseudoinclusions of extracellular edematous matrix.

Distribution and role of myofibroblasts in human normal seminal vesicle stroma.

We studied the distribution of myofibroblasts in the stroma of normal seminal vesicles. Twelve normal seminal vesicles obtained by surgery on the diagnosis of some diseases were selected, and we evaluated the distribution of myofibroblasts in the seminal vesicles using immunohistochemical and electron and immunoelectron microscopic techniques. Immunohistochemically, myofibroblasts, which were positive for alpha-smooth muscle actin (ASMA) and negative for high molecular weight caldesmon (h-CD), were observed in the stroma just beneath the epithelium of normal seminal vesicles. Moreover, an electron microscope examination revealed the presence of spindle or stellate cells in the stroma of the lamina propria beneath the seminal vesicle epithelium, and an immunoelectron microscopic examination showed that these cells were positive for ASMA. Finally, myofibroblasts are distributed in the lamina propria of human normal seminal vesicles and may play an important role in the ejection of sperm plasm.

CAM5.2-positive subserosal myofibroblasts in appendicitis.

In this study, we examined the distribution and origin of myofibroblasts around the perforations of appendicitis. Stromal cells of 45 cases were studied by immunohistochemistry. In the normal appendix, myofibroblasts were restricted to the mucosa, and CD34-positive stromal cells were distributed in the submucosal and subserosal layers. Some mesothelial cells were positive for cytokeratin CAM5.2, cytokeratin 5, or mesothelial cells (HBME-1). In perforation of appendicitis with both abscess and granulation tissue, a small to moderate or a moderate to large number of myofibroblasts appeared in the subserosal area around the perforation, respectively, but CD34-positive stromal cells were completely absent there. In the subserosal area of the perforation of appendicitis with abscess, cytokeratin 5-positive stromal cells were absent. However, a small to moderate number of cytokeratin CAM5.2-positive stromal cells were observed there. Double immunostaining showed the coexpression of alpha-smooth muscle actin (ASMA) and cytokeratin CAM5.2 and the coexpression of cytokeratin 5 and cytokeratin CAM5.2 in many or some stellate-shaped or spindle-shaped stromal cells existing in the subserosal area with granulation tissue around the perforation of appendicitis, respectively. Finally, many myofibroblasts appearing in the subserosal area of the perforation of appendicitis may be derived from submesothelial cells or mesothelial cells.

Increased iron deposition in rat liver fibrosis induced by a high-dose injection of dimethylnitrosamine.

Using a developed rat model of hepatic necrosis and subsequent fibrosis induced by a high-dose intraperitoneal injection of dimethylnitrosamine (DMN), we studied iron deposition and expression of transforming growth factor-beta(1) (TGF-beta(1)) during the development of persistent liver fibrosis. Rats were sacrificed at several timepoints from 6 h to 10 months post-injection and the livers were examined for iron content and distribution, and for expression of alpha-smooth muscle actin, ED-1, TGF-beta(1), and collagen (alpha(2))I. Morphologic evidence of acute submassive hemorrhagic necrosis peaked at 36 h; on day 3 the residual parenchyma contained activated hepatic stellate cells (HSCs) and necrotic areas contained numerous macrophages; and on day 5, necrotic tissues and erythrocytes had been phagocytosed and macrophages contained abundant iron deposits. From days 7 to 10, iron-laden macrophages and activated HSCs (myofibroblasts) populated the fibrous septa in parallel. From week 2 to month 10, closely arranged macrophages and myofibroblasts were found in central-to-central bridging fibrotic tissue. TGF-beta(1) was strongly detected in both macrophages and HSCs during development of liver fibrosis. Our data suggest that increased iron deposition may be involved in the initiation and perpetuation of rat liver fibrosis. Iron-laden macrophages may influence HSCs through the action of TGF-beta(1) in DMN-induced liver fibrosis.

[Non-alcoholic steatohepatitis : pathology and pathogenesis].

Nonalcoholic steatohepatitis (NASH) has become to be widely recognized as a significant cause of chronic liver injuries. Evidences suggest that development of NASH requires a double "hit". The "first hit" involves the accumulation of fat in the liver, and the "second hit" includes oxidative stress, cytokines, stellate cell activation, and fibrogenesis. Microscopically, some alcoholic hepatitis-like findings, hepatocellular steatosis, ballooning degeneration, Mallory body, acute and chronic lobular inflammation, and zone 3 perisinusoidal fibrosis are noted. Because ballooning degeneration and Mallory body denote progressive NASH, we should identify clearly these findings. The diagnosis of nonalcoholic steatohepatitis requires histopathologic evaluation, because the lesions of parenchymal injury and fibrosis cannot be detected by imaging studies or laboratory tests.

Vascularization in tissue remodeling after rat hepatic necrosis induced by dimethylnitrosamine.

We observed postnecrotic tissue remodeling to examine vascularization in adult rat livers. Livers, bone marrow, and peripheral blood from rats at 24 h to 14 days after an injection of dimethylnitrosamine (DMN) were examined by light microscopic, immunohistochemical, and ultrastructural methods. Numerous ED-1 (a marker for rat monocytes/macrophages)-positive round mononuclear cells infiltrated in the necrotic areas at 36 h after DMN treatment. On day 5, when necrotic tissues were removed, some of the cells were transformed from round to spindle in shape. On day 7, these cells were contacted with residual reticulin fibers and became positive for SE-1, a marker of hepatic sinusoidal endothelial cells and Tie-1, an endothelial cell-specific surface receptor, associated with frequent occurrence of ED-1/SE-1 and ED-1/Tie-1 double-positive spindle cells. Ultrastructurally, the spindle cells simultaneously showed phagocytosis and endothelial cell-like morphology. With time necrotic areas diminished, and on day 14, the necrotic tissues were almost replaced by regenerated liver tissues and thin bundles of central-to-central bridging fibrosis. Bone marrow from 12 h to day 2 showed an increase of BrdU-positive mononuclear cells. Some of them were positive for ED-1. The BrdU-labeled and ED-1-positive cells appeared as early as 12 h after DMN injection and reached a peak in number at 36 h. They were similar in structure to ED-1-positive cells in necrotic liver tissues. These findings suggest that round mononuclear ED-1-positive cells proliferate first in bone marrow after DMN treatment, reach necrotic areas of the liver through the circulation, and differentiate to sinusoidal endothelial cells. Namely, hepatic sinusoids in DMN-induced necrotic areas may partly be reorganized possibly by vasculogenesis.