Palisading Adenocarcinoma: A Morphologically Unique Salivary Gland Tumor With a Neuroendocrine-like Appearance and a Predilection for the Sublingual Glands of Women.

Adenocarcinoma, not otherwise specified (NOS) is a heterogenous group of salivary gland tumors that likely contains distinct tumors that have not yet been characterized. Indeed, in recent years, cases previously diagnosed as adenocarcinoma, NOS have been recategorized into novel tumor designations such as secretory carcinoma, microsecretory adenocarcinoma, and sclerosing microcystic adenocarcinoma. We sought to describe a distinctive, hitherto-undescribed salivary gland tumor encountered in the authors' practices. Cases were pulled from the surgical pathology archives of the authors' institutions. Histologic, immunohistochemical, and clinical findings were tabulated, and targeted next-generation sequencing was performed on all cases. Nine cases were identified, arising in 8 women and 1 man ranging from 45 to 74 years (mean, 56.7 y). Seven tumors (78%) arose in the sublingual gland, while 2 (22%) arose in the submandibular gland. The cases shared a distinctive morphologic appearance. They were biphasic, with ducts scattered among a predominant polygonal cell with round nuclei, prominent nucleoli, and pale eosinophilic cytoplasm. These cells were arranged as trabeculae and palisaded as pseudorosettes around hyalinized stroma and vessels, resembling a neuroendocrine tumor. Four of the cases were well-circumscribed, while the remaining 5 showed infiltrative growth including perineural invasion in 2 (22%) and lymphovascular invasion in 1 (11%). Mitotic rates were low (mean, 2.2/10 HPFs); necrosis was absent. By immunohistochemistry, the predominant cell type was strongly positive for CD56 (9 of 9) and variably positive for pan-cytokeratin (AE1/AE3) (7 of 9) with patchy S100 (4 of 9), but negative for synaptophysin (0 of 9) and chromogranin (0 of 9), while the ducts were strongly positive for pan-cytokeratin (AE1/AE3) (9 of 9) and CK5/6 (7 of 7). Next-generation sequencing did not reveal any fusions or obvious driver mutations. All cases were resected surgically, with external beam radiation also done in 1 case. Follow-up was available in 8 cases; there were no metastases or recurrences after 4 to 160 months (mean, 53.1 mo). A dual population of scattered ducts with a predominance of CD56-positive neuroendocrine-like cells characterizes a unique salivary gland tumor which is often encountered in the sublingual glands of women, for which we propose the term "palisading adenocarcinoma." Although the tumor was biphasic and had a neuroendocrine-like appearance, it lacked convincing immunohistochemical evidence of myoepithelial or neuroendocrine differentiation. Although a subset showed unequivocally invasive growth, this tumor appears to behave in an indolent manner. Moving forward, recognition of palisading adenocarcinoma and its separation from other salivary adenocarcinomas, NOS will facilitate a better understanding of the characteristics of this previously unrecognized tumor.

Spindle Cell Variant of Ameloblastic Carcinoma: Another Example in a Japanese Male.

Spindle cell variant of ameloblastic carcinoma (SpCAC) is a rare subtype of ameloblastic carcinoma. Herein, we describe an additional case of SpCAC of the mandible of a 76-year-old Japanese male. We discuss diagnostic problems we encountered in this case, focusing on unusual expression of myogenic/myoepithelial markers, such as smooth muscle actin and calponin.

A case of esophageal carcinoma on esophageal varices treated by endoscopic submucosal dissection after endoscopic injection sclerotherapy.

Esophageal varices (EVs) are often treated using endoscopic injection sclerotherapy. Endoscopic submucosal dissection (ESD) has been used for early esophageal epithelial neoplasia worldwide. We report a case of early esophageal squamous cell carcinoma (ESCC) that occurred over EVs, in which the EVs were treated with endoscopic injection sclerotherapy before the early ESCC was treated with endoscopic submucosal dissection. Argon plasma coagulation was finally performed to prevent the recurrence of varices. No serious complications, such as severe bleeding or perforation, were observed. Histopathological examination revealed submucosal veins occluded with an organized thrombus for which endoscopic injection sclerotherapy with an intravariceal injection of sclerosant had been performed, but no fibrosis was observed outside the blood vessels. This explains that the injected sclerosant into EVs did not cause any tissue reaction like fibrosis in the submucosa surrounding the vein, which may have made endoscopic submucosal dissection safer and easier. Varices have not recurred, and ESCC has also not recurred for 5 years. We demonstrated a successful treatment of ESCC on EVs and no submucosal fibrosis other than inside the occluded vessels and verified it histologically.

Pancreatic neuroendocrine carcinoma with unique morphological features mimicking intraductal papillary mucinous carcinoma: A case report.

Background: Pancreatic neuroendocrine carcinoma (PanNEC) is a rare disease entity with rapid progression and poor prognosis. Here, we report a PanNEC case with unique morphological features mimicking intraductal papillary mucinous carcinoma. Case presentation: A 69-year-old Japanese man was referred to our hospital for further evaluation of weight loss and deterioration of diabetes mellitus. Contrast-enhanced computed tomography showed a solid and cystic mass with hypo-enhancement at the tail of the pancreas. The main pancreatic duct (MPD) was diffusely dilated without obstruction, accompanied by marked parenchymal atrophy. Multiple peritoneal and omental nodules were observed, suggesting tumor dissemination. Endoscopic retrograde cholangiopancreatography revealed that the mass correlated with the dilated MPD. During pancreatography, a large amount of mucus was extruded from the pancreatic orifice of the ampulla. Based on these imaging findings, intraductal papillary mucinous carcinoma was suspected. Per-oral pancreatoscopy (POPS)-guided tumor biopsies were conducted for the lesion's solid components. Histopathological examination of the biopsied material confirmed small-cell-type PanNEC with a Ki-67 labeling index of 90%. Due to his condition's rapid decline, the patient was given the best supportive care and died 28 days after diagnosis. Conclusion: Although rare, PanNEC, which correlates with the MPD and is accompanied by marked dilation of the MPD, does exist as one phenotype. In such cases, POPS-guided biopsy could be a useful diagnostic modality.

Transient atypical lymphoplasmacytic proliferation of the endometrium associated with pyometra: a case report.

Plasmablastic lymphoma is a mature B-cell neoplasm with plasmablastic differentiation, often associated with human immunodeficiency virus (HIV) infection and other forms of immunosuppression. Although it is usually an aggressive disease, spontaneous regression has been seen in a few cases. Plasmablastic lymphoma of the uterus is rare. We report a case of atypical lymphoplasmacytic proliferation resembling plasmablastic lymphoma associated with pyometra that disappeared completely as the pyometra resolved. A 76-year-old HIV-negative woman presented with abnormal vaginal bleeding. Ultrasound and MRI findings were consistent with pyometra diagnosis. Endometrial biopsy revealed large plasmablastoid cells with abundant cytoplasm and prominent nucleoli proliferating in the endometrium. Immunohistochemistry showed that large cells stained positive for CD138, CD79a, and MUM1, and negative for CD20, PAX5, CD3, and CD5. Ki67 labelled at least 80% of the large cells. Epstein-Barr virus was detected in a small number of cells. The histologic picture was highly indicative of lymphoma, especially plasmablastic lymphoma, though the clinical context was unusual. As the pyometra was treated and resolved, the intrauterine abnormality disappeared completely. The patient has been well after 16 months with no sign of recurrent disease. This case underscores the sometimes blurry distinction between benign inflammation and lymphoma.

Yolk Sac Tumor in a Recurrence of Colonic Adenocarcinoma With Shared Mutations in APC and TP53 Genes: A Case Report.

Only four cases of colorectal adenocarcinoma with a yolk sac tumor (YST) component have been reported in the English literature. No genetic investigation has been performed in these cases. We report a case of colorectal adenocarcinoma in which the recurrent tumor had a YST component. A 49-year-old woman presented with a pelvic tumor three years after endoscopic mucosal resection of sigmoid colon adenocarcinoma. The pelvic tumor consisted of an undifferentiated carcinoma component and a YST component. The serum alpha-fetoprotein level was elevated to 42 ng/mL. Treatment as conventional colorectal carcinoma produced some anticancer effects, but the patient died 14 months after the recurrence and 49 months after the EMR. With the help of the next-generation sequencing results of the recurrent tumor, APC c.835 - 8A > G and TP53 c.524G > A (p.R175H) mutations were identified by direct sequencing in both the primary and the recurrent tumors, confirming the relationship between the two metachronous tumors.

The Diagnosis and Treatment of Primary Pulmonary Artery Sarcoma: Two Case Reports.

Pulmonary artery sarcoma (PAS) is considered a very rare tumor with a poor prognosis. We herein report two cases of PAS that were diagnosed by positron emission tomography (PET)/computed tomography (CT). In both cases, PET was an effective option for diagnosing tumors, and surgical resection was a valid treatment for these diseases. If a pulmonary artery tumor is suspected, PET/CT is useful for diagnosing PAS and very helpful for choosing the surgical treatment strategy.

Clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) are widely used to treat advanced metastatic cancers. Neutralisation of PD-1 or CTLA-4 by ICIs results in immune-related adverse events (irAEs). The clinicopathological features of twelve patients with hepatic irAEs were evaluated and compared to those of ten patients with autoimmune hepatitis (AIH) or graft-versus-host disease (GVHD). No significant difference was seen in serum levels of transaminases, whereas serum levels of IgG and anti-nuclear antibody were higher in patients with AIH than in those with GVHD or hepatic irAEs. Inflammation was limited to the liver lobes in patients with GVHD or hepatic irAEs, whereas patients with AIH exhibited both portal and lobular inflammation. Immunohistochemical analyses revealed a predominant infiltration of CD8+ T cells and defective accumulation of regulatory T cells (Tregs) expressing forkhead box p3 (FOXP3) in the lobular areas of patients with hepatic irAEs and GVHD. In contrast, periportal lesions of patients with AIH were characterised by an infiltration of CD4+ T cells, CD8+ T cells, CD20+ B cells, and FOXP3+ Tregs. Overall, the activation of CD8+ T cells in the absence of activation of Tregs potentially underlies the immunopathogenesis of hepatic irAEs.

Orbital abscess caused by Exophiala dermatitidis following posterior subtenon injection of triamcinolone acetonide: a case report and a review of literature related to Exophiala eye infections.

BACKGROUND: Subtenon injection of triamcinolone acetonide (STTA) has been widely adopted in the clinical setting of ophthalmology and its infectious complications are rare. However, orbital abscess following STTA has been reported in seven cases. Furthermore, although eye infections due to Exophiala species are uncommon, there have been 19 cases to date. E. jeanselmei, E. phaeomuriformis, E. werneckii, and E. dermatitidis have been reported to cause human eye infections; however, to the best of our knowledge, orbital abscess caused by E. dermatitidis has not yet been reported. We describe the first documented case of fungal orbital abscess caused by E. dermatitidis following STTA. We also review the related literature of orbital abscess following STTA, as well as eye infections caused by the four Exophiala species. CASE PRESENTATION: The patient was a 69-year-old Japanese woman with diabetic mellitus. She had a macular oedema in her right eye, which occurred secondary to branch retinal vein occlusion. An orbital abscess caused by E. dermatitidis occurred 4 months after the second STTA for the macular oedema, which was successfully treated by a surgical debridement and systemic administration of voriconazole. CONCLUSIONS: Our findings in the patient and from our literature survey caution ophthalmologists to the fact that STTA can cause fungal orbital infections, especially in diabetic patients. Furthermore, surgical treatment is one of the most important risk factors.

18F-FDG PET/CT Finding of Primary Cardiac Lymphoma.

An 80-year-old woman experienced dyspnea. Cardiac enlargement was detected by chest radiography at a local hospital. She was admitted to our hospital, and echocardiography and CT revealed pericardial effusion and multiple tumor lesions in right atrium. F-FDG PET/CT demonstrated multiple nodular accumulations in these tumors (SUVmax, 14.5). Cytologic analysis of the pericardial fluid revealed a diffuse large B-cell lymphoma. Primary cardiac lymphoma (PCL) is rare, and there are few reports about the F-FDG PET/CT imaging features of PCLs. In high F-FDG uptake in multiple tumors in the right atrium and large pericardial effusion, a PCL should be considered.

Ectopic TWEAKR expression in type I fiber of stroke-prone spontaneously hypertensive rats is related to slow muscle-specific hypotrophy.

AIMS: Stroke-prone spontaneously hypertensive rats (SHRSP) show significantly lower body weight than normotensive Wistar-Kyoto rats (WKY). Our hypotheses are as follows: weight loss of the skeletal muscle is related to hypertension-related diseases, and muscle hypotrophy is useful as a therapeutic target for hypertension and hypertension-related diseases. In this study, we aimed to investigate the pathophysiological characteristics of muscle hypotrophy in SHRSP to determine the therapeutic target molecule(s). MAIN METHODS: The difference in skeletal muscles in the lower leg between WKY and SHRSP was evaluated mainly through weight/tibial length, histological, gene expression, and protein expression analyses. KEY FINDINGS: SHRSP had a significantly lower weight/tibial length in soleus and gastrocnemius, but not in plantaris and tibialis anterior, indicating that muscles consisting of a relatively high amount of slow muscle fiber were affected. This result was confirmed by the histological analysis of soleus, showing that type I fiber mainly decreased the fiber size. Microarray and protein expression analyses showed that the muscle-specific ubiquitin ligase, muscle RING finger 1 (MuRF1), but not atrogin-1, was highly expressed in soleus, but not in plantaris, in SHRSP. TNF-like weak inducer of apoptosis receptor (TWEAKR) was predicted as a MuRF1 up-regulator by Ingenuity Pathway Analysis and immunostained only in type II fiber in WKY but in both type I and II fibers in SHRSP. SIGNIFICANCE: TWEAKR is a type II-specific receptor in the skeletal muscle. Ectopic TWEAKR expression in type I fiber of SHRSP is most likely involved in slow muscle-specific hypotrophy through MuRF1 overexpression.

An 18-Year-Old Male With X-linked Lymphoproliferative Syndrome Type 1 Who Developed Primary Central Nervous System Lymphoma 6 Months After Primary Epstein-Barr Virus Infection.

X-linked lymphoproliferative syndrome type 1 (XLP1) is a rare congenital immunodeficiency disease. We report the case of an 18-year-old male who developed hemophagocytic lymphohistiocytosis (HLH) with neurologic complications after primary Epstein-Barr virus (EBV) infection and subsequently developed EBV-related central nervous system lymphoma (CNSL). Given the vulnerability to EBV, he was finally diagnosed with XLP1 and treated with whole-brain irradiation along with chemotherapy and subsequent allogeneic hematopoietic stem cell transplantation from a SH2D1A wild-type sibling donor. Although the prognosis for CNSL is generally dismal, reconstitution of the immune system from a normal donor contributed to the patient remaining in remission for 30 months.

Impact of sirolimus treatment for refractory kaposiform hemangioendothelioma with exacerbation of the disease 10 years after initial diagnosis.

We describe our experience with a 12 year-old girl with kaposiform hemangioendothelioma accompanied by Kasabach-Merritt phenomenon with exacerbation of the disease 10 years after the initial diagnosis. Kaposiform hemangioendothelioma infiltrated into the subcutaneous tissue of the facial skin with deterioration of coagulopathy despite conventional therapies including corticosteroid, vincristine, and propranolol. Sirolimus, a mammalian target of rapamycin inhibitor, produced rapid and dramatic improvement of the Kasabach-Merritt phenomenon and kaposiform hemangioendothelioma shrinkage. Eventually, multifocal lesions of kaposiform hemangioendothelioma disappeared on the images of magnetic resonance imaging and have remained in remission for 27 months after sirolimus cessation. We demonstrated that the AKT/mammalian target of rapamycin signaling pathway played a pivotal role in the kaposiform hemangioendothelioma growth. Sirolimus must be a strong candidate for molecular therapy targeting kaposiform hemangioendothelioma.

MR imaging features of mammary analogue secretory carcinoma and acinic cell carcinoma of the salivary gland: a preliminary report.

OBJECTIVES: To report MR imaging features of mammary analogue secretory carcinoma (MASC) and acinic cell carcinoma (AciCC) of the salivary gland based on the latest version of the World Health Organization (WHO) 2017 classification of head and neck tumours. METHODS: MR images in 4 patients with MASC and 4 with AciCC were reviewed for margin characteristics, the presence of pathological cervical nodes, the presence of a cystic component and interface between cystic and solid component, signal intensity of the cystic components on T1 weighted images, and signal intensity of the solid component on T1 and T2 weighted images. RESULTS: All the MASCs and AciCCs had well-defined boundaries, and 1 AciCC had pathological nodes. All 4 MASCs presented as predominantly cystic tumours with papillary projection of the solid component. All 4 AciCCs presented as solid tumours. The signal intensity of the cystic components on T1 weighted images was entirely hyperintense in 2, and partly hyperintense demonstrating fluid-fluid level in 2. In all the MASCs, the signal intensity of the solid components on T1 weighted images was intermediate. In the AciCCs, the signal intensity of the solid components on T1 weighted images was high in 2 tumours and intermediate in 2. The signal intensity of the solid components on T2 weighted images varied from low to high in both MSACs and AciCCs. CONCLUSIONS: All 4 MASCs had a large cystic component, including areas of high signal intensity on T1 weighted images. The solid component appeared as a papillary projection into the cystic component. All 4 AciCCs presented as solid tumours, 2 of which showed high signal intensity on T1 weighted images.

Imaging and clinicopathological features of nivolumab-related cholangitis in patients with non-small cell lung cancer.

Background Nivolumab demonstrates promising efficacy for the treatment of non-small cell lung cancer and other malignancies. The clinical benefit of nivolumab, however, may be hampered by specific immune-related adverse events (irAEs), and little is known regarding nivolumab-related cholangitis. Methods A computerized search of our clinical database identified 3 metastatic non-small cell lung cancer patients with nivolumab-related cholangitis. All patients were treated with intravenous nivolumab monotherapy (3.0 mg/kg) every 2 weeks until disease progression or irAEs occurred. Clinical data regarding the duration of nivolumab treatment, symptoms, laboratory abnormalities, pathological findings of liver parenchyma biopsy specimens, and management of nivolumab-related cholangitis were analyzed. Results Our analysis revealed that nivolumab-related cholangitis was characterized by (1) localized extrahepatic bile duct dilation without obstruction; (2) diffuse hypertrophy of the extrahepatic bile duct wall; (3) a dominant increase in the biliary tract enzymes alkaline phosphatase and gamma-glutamyl transpeptidase relative to the hepatic enzymes aspartate and alanine aminotransferase; (4) normal or reduced levels of the serum immunological markers antinuclear antibody, antimitochondrial antibody, smooth muscle antibody, and immunoglobulin G4; (5) the pathological finding of biliary tract cluster of differentiation 8-positive T cell infiltration from liver biopsy; and (6) a moderate to poor response to steroid therapy. Conclusions Nivolumab-related cholangitis is associated with distinct imaging and clinicopathological features that distinguish it from acute cholangitis of common etiologies and other immune-related cholangitis. Further studies are warranted to establish the optimal management of patients with this irAE.

Report of two cases of pseudoprogression in patients with non-small cell lung cancer treated with nivolumab-including histological analysis of one case after tumor regression.

The recent approval of nivolumab and other immune-checkpoint inhibitors for the treatment of certain solid tumors including non-small cell lung cancer (NSCLC) has transformed cancer therapy. However, it will be important to characterize effects of such agents not seen with classical cytotoxic drugs or other targeted therapeutics. We here report two cases of NSCLC showing so-called pseudoprogression during nivolumab treatment. In both cases, imaging assessment revealed that liver metastatic lesions initially progressed but subsequently shrank during continuous nivolumab administration, with treatment also resulting in a decline in serum levels of carcinoembryonic antigen. Histological evaluation of the liver metastatic lesion of one case after regression revealed fibrotic tissue containing infiltrated lymphocytes positive for CD3, CD4, or CD8 but no viable tumor cells, suggestive of a durable immune reaction even after a pathological complete response. Given the increasing use of immune-checkpoint inhibitors in patients with NSCLC or other solid tumors, further clinical evaluation and pathological assessment are warranted to provide a better understanding of such pseudoprogression.

Metastases to the parotid nodes: CT and MR imaging findings.

OBJECTIVES: To present and characterize CT and MR imaging findings of metastases to the parotid nodes. METHODS: CT (n = 10) and MR (n = 11) images from 14 patients with metastases to the parotid nodes were reviewed. The primary tumour sites were the ocular adnexa in five patients, facial skin in four patients, upper aerodigestive tract in four patients and thyroid gland in one patient. CT and MR images were evaluated with emphasis on the size and number of parotid tumours, their location in the parotid gland, the presence of associated clinically pathological cervical nodes or previous history of cervical node metastasis, margin characteristics and the presence of central necrosis. RESULTS: A total of 18 tumours were identified in 14 patients, with an average maximal cross-sectional diameter of 19 mm (7-44 mm). 12 patients had a single parotid tumour and 2 patients had unilateral multiple tumours; 12 tumours in 10 patients were located in the parotid tail, 6 tumours in 4 patients were located in the superficial lobe and no tumour was noted in the deep lobe. In the superficial lobe, four of six tumours were located in the pretragal area. Three of nine patients whose primary sites were the ocular adnexa or skin had associated clinically pathological cervical nodes. None of these patients had a previous history of cervical node metastasis. All five patients with other primary sites had associated pathological cervical nodes or a history of such. 11 tumours had well-defined margins and 7 tumours had ill-defined margins. Post-contrast images showed central necrosis in 2 of 11 tumours. CONCLUSIONS: Metastases to the parotid nodes tend to present as solitary parotid masses with two preferential sites.