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Mesenchymal-epithelial transition (MET) exon 14-skipping mutation (METex14) is rare in pulmonary invasive mucinous adenocarcinomas (IMAs), and the clinical impact of MET-tyrosine kinase inhibitors (TKIs) remains unknown. We herein report a 75-year-old woman with IMA harboring METex14 who was treated with the MET-TKI tepotinib. The lung tumor regressed over six months; however, the patient ultimately died of exacerbated interstitial lung disease (ILD), possibly associated with tepotinib. An autopsy revealed diffuse alveolar damage in preexisting chronic fibrosis. We discuss how to pre-evaluate ILD deterioration risks and monitor TKI-induced lung toxicity during treatment.
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Cystic brain metastasis is a rare condition that mainly originates from lung or breast adenocarcinomas. By contrast, pulmonary spindle cell carcinoma, a rare type of non-small cell carcinoma, has not been reported with this condition. Cystic brain metastases are characterized by larger tumor sizes with increased peritumoral edema compared with solid metastases. Therefore, specific treatment strategies are required for intracranial disease control. Immunotherapy has recently been demonstrated to be crucial for treating pulmonary sarcomatoid carcinomas based on high programmed cell death-ligand 1 (PD-L1) expression observed in these cancers. The present report describes the case of an 82-year-old man diagnosed with pulmonary spindle cell carcinoma, a rare subtype of sarcomatoid carcinoma. At 7 months after the diagnosis, the patient complained of a walking disturbance for which de novo brain metastasis with peritumoral edema was the causative agent. The brain tumor had a large cystic component, and thus, an Ommaya reservoir catheter was implanted for cyst aspiration but collapsed early without sufficient volume reduction. The patient was transferred to receive twice-split gamma knife treatment, which shrank the solid compartment and reduced the cyst volume, thereby relieving neurological defects. The patient was subsequently treated with immunotherapy targeting programmed cell death-1 based on the high PD-L1 expression in the lung tumor specimen. The thoracic tumors regressed following immunotherapy and progression-free survival was maintained for 16 months. To the best of our knowledge, the present report provides the first description of focal and systemic therapies for pulmonary spindle cell carcinoma with cystic brain metastasis. The report also discusses the treatment strategies for cystic brain metastases and reviews cases of pulmonary spindle cell carcinoma treated with immune checkpoint inhibitors.
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BACKGROUND: Polymorphous adenocarcinoma is a common intraoral minor salivary gland carcinoma in Western countries but is extremely rare in Japan. The current study aimed to characterize the clinicopathological features and status of molecular alterations of polymorphous adenocarcinoma-associated genes, such as PRKD1/2/3, ARID1A, and DDX3X, in a large cohort of Japanese patients with polymorphous adenocarcinoma. METHODS: We examined the cases of 36 Japanese patients with salivary gland polymorphous adenocarcinoma and 26 cases involving histopathological mimics. To detect gene splits, fluorescence in situ hybridization was carried out for polymorphous adenocarcinoma-associated genes. Additionally, we applied a SNaPshot multiplex assay to identify PRKD1 hotspot mutations. RESULTS: This study revealed the indolent clinical course of polymorphous adenocarcinoma with a high 10-year overall survival rate (92.9%), accompanied by occasional local recurrences and cervical lymph node metastasis (23.3%). Twenty cases (55.6%) of polymorphous adenocarcinoma (but none of the mimics) exhibited alterations in at least one polymorphous adenocarcinoma-associated gene. Rearrangement of polymorphous adenocarcinoma-associated genes and PRKD1 E710D were identified in 17 (47.2%) and 4 (11.1%) cases, respectively; one case showed coexisting PRKD3 split and PRKD1 E710D. In the multivariate analysis, high clinical stage (p = 0.0005), the presence of prominent nucleoli (p = 0.0003), and ARID1A split positivity (p = 0.004) were independent risk factors for disease-free survival. CONCLUSION: Japanese patients with polymorphous adenocarcinoma showed clinicopathological features similar to those reported in Western countries. This study disclosed that polymorphous adenocarcinoma-associated genetic alterations were common and specific findings in polymorphous adenocarcinomas. The diagnostic role and possible prognostic significance of polymorphous adenocarcinoma-associated genetic alterations in polymorphous adenocarcinomas were suggested.
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Adenocarcinoma , Neoplasias das Glândulas Salivares , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Humanos , Hibridização in Situ Fluorescente , Japão , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologiaRESUMO
Lipoid pneumonia presents with a variety of lung abnormalities, particularly mass forming lesions that mimic lung cancers. While 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) is expected to discriminate both diseases, some previous reports showed pseudo-positive FDG uptake in lipoid pneumonia. Here, we report a case of pathologically proven chronic lipoid pneumonia in a 78-year-old Japanese man. Computed tomography (CT) showed multi-lobar mass-forming lesions with a fat-density. PET confirmed the spotty accumulation of FDG in the corresponding fat-density area on CT, suggesting lipoid pneumonia. We reviewed the literature and discussed the FDG uptake patterns in lipoid pneumonia.
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Granular cell tumours (GCTs) are a rare form of neoplasm found throughout the body. Tracheobronchial involvement is less common. We describe a case of tracheal GCT in a 37-year-old Japanese woman presenting with throat discomfort. A tracheal tumour was found during laryngoscopy for undefined throat discomfort. Bronchoscopy demonstrated a white sub-epithelial solitary nodule on the tracheal wall, and pathological examination of the biopsy samples confirmed GCT. No therapeutic procedures were performed, and the tumour is currently under strict observation. Throat discomfort is a rare presentation of tracheal tumours, but an early inspection using laryngoscopy and bronchoscopy may be helpful in determining an accurate diagnosis.
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Pulmonary sclerosing pneumocytoma (PSP) is a rare benign neoplasm of the lung that shows a slow growing pattern. Corresponding contrast-enhancements on chest computed tomography (CT) vary widely in both patterns and degrees. However, gross intratumoral radiolucencies, attributable to cyst formation, necrosis, or intratumoral hematoma, were rarely reported in PSP cases. We herein report on a case involving a 61-year-old Japanese women with PSP demonstrating CT-defined intratumoral radiolucency. A chest CT scan revealed a solitary and well-circumscribed nodule that showed a substantial growth over a 7-year period. The tumor was composed of a solid portion visualized with contrast-enhancement and a central radiolucency on a chest CT scan. A positron emission tomography scan revealed high uptake of fluorodeoxyglucose on the solid portion of the tumor, but the radiolucent portion showed negative uptake. The examination of a tumor specimen obtained by a percutaneous core needle biopsy aided in determining a pathological diagnosis of PSP, and the patient subsequently received a right lower lobectomy of the lung. The portion of central radiolucency on the CT scan corresponding to the surgical specimen was pathologically proven to be gross hematoma.
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BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare soft tissue tumor that generally involves the retroperitoneum, pelvis, omentum and mesentery in younger patients. However, extra-abdominal DSRCT is very rare. CASE PRESENTATION: A 49-year-old Japanese man noticed a mass in the right parotid gland. Ultrasound examination revealed a solid tumor about 2 cm in diameter. Computed tomography (CT) of the whole body revealed no other tumors or lymph node swelling. Superficial parotidectomy was performed. Histologically, the tumor was composed of various-sized tumor cell nests in an abundant fibromyxoid and collagenous background. The tumor cells were small to medium-sized. Immunohistochemistry showed that the tumor cells were immunoreactive for epithelial markers and desmin. They also showed strong nuclear staining with a Wilms tumor 1 (WT1) antibody detecting the C-terminal region (C-WT1), but not the N-terminal region (N-WT1). We also performed 3'/5' expression imbalance assay based on reverse transcription polymerase chain reaction (RT-PCR) to determine whether aberrant WT1 gene expression was present. This tumor was found to lack 5'-regional expression of the WT1 gene, as well as immunoreactivity with the N-WT1 antibody. Finally, fluorescence in situ hybridization (FISH) and RT-PCR analyses revealed the presence of a gene showing fusion between exon 7 of EWSR1 and exon 8 of WT1. The tumor was diagnosed as a DSRCT of the right parotid gland. The patient has been followed for 3 years without recurrence or metastasis. CONCLUSIONS: Although DSRCT in the salivary gland is extremely rare, it should be included in the differential diagnosis of poorly differentiated salivary gland neoplasms, especially with a fibromyxoid background. Pathologists should bear in mind that DSRCT may occur in major salivary glands and should perform immunohistochemistry with appropriate antibodies, not only those against keratin and desmin, but also one detecting the C-terminal region of WT-1. Furthermore, molecular detection of EWSR1-WT1 fusion gene conclusively confirmed the diagnosis of DSRCT in this uncommon location.
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Tumor Desmoplásico de Pequenas Células Redondas/diagnóstico por imagem , Neoplasias Parotídeas/diagnóstico por imagem , Proteína EWS de Ligação a RNA/genética , Proteínas WT1/genética , Tumor Desmoplásico de Pequenas Células Redondas/genética , Tumor Desmoplásico de Pequenas Células Redondas/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/patologia , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologiaRESUMO
Pulmonary artery intimal sarcoma (PAIS) is a rare mesenchymal malignancy arising in the pulmonary trunk or proximal pulmonary artery and shows intraluminal growth. Clinical manifestations in PAIS are predominantly related to the pulmonary artery embolism, so cases with initial symptoms related to an extrapulmonary metastasis are unusual. The present report describes an 82-year-old man without any cardiopulmonary symptoms who was detected with an abnormal shadow on chest radiography during a routine health checkup. Contrast medium-enhanced chest computed tomography revealed an enhancing mass in the right pulmonary artery, pulmonary nodules, and a chest wall tumor corresponding to the abnormal shadow observed using chest radiography. A core needle biopsy for the chest wall tumor determined a pathological diagnosis of unclassified sarcoma. The patient was diagnosed with PAIS on the basis of clinical, radiological, and pathological correlations. He was scheduled to receive supportive care, but died of respiratory failure 1 year from the first visit. An autopsy revealed the pleomorphic sarcoma occupying the entire lumen of the right pulmonary artery with the only site of extrapulmonary metastasis in the chest wall. We should be aware of rare cases of asymptomatic PAIS found through routine health checkups.
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BACKGROUND AND AIMS: The current goal of treatment for ulcerative colitis [UC] is endoscopic and ultimately histological mucosal healing. However, there is no consensus on the definition of histological mucosal healing. We evaluated histological risk factors for clinical relapse in UC patients with endoscopically normal mucosa to focus on the importance of histological evaluation. METHODS: Patients with UC who underwent colonoscopy confirming Mayo endoscopic subscore [MES] ≤ 1 with biopsies were enrolled into this retrospective cohort. Three expert pathologists evaluated the presence or absence of chronic inflammatory cell infiltrate, breaches in the surface epithelium, crypt abscesses, mucin depletion, crypt architectural irregularities and basal plasmacytosis. Clinical relapse was defined as partial Mayo score ≥ 3 or modification of induction treatment. Prediction models of clinical relapse were generated, especially in patients with MES 0. RESULTS: A total of 194 UC patients were enrolled. Histological abnormalities existed more frequently in patients with MES 1 than those with MES 0, while the vast majority of patients still possessed at least one abnormality. There was no significant difference in time to relapse between MES 0 and 1. Crypt architectural irregularities and mucin depletion were associated with time to relapse in patients with MES ≤ 1. In patients with MES 0, the presence of mucin depletion was the only factor significantly and independently associated with the risk of relapse (hazard ratio, 2.18 [1.16-5.82]; p = 0.03). CONCLUSIONS: Mucin depletion was shown to be a histological risk factor for clinical relapse in UC patients with MES 0.
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Colite Ulcerativa/diagnóstico por imagem , Colite Ulcerativa/patologia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Adulto , Biópsia , Colite Ulcerativa/metabolismo , Colonoscopia , Feminino , Humanos , Mucosa Intestinal/metabolismo , Masculino , Pessoa de Meia-Idade , Mucinas/metabolismo , Variações Dependentes do Observador , Valor Preditivo dos Testes , Recidiva , Fatores de RiscoRESUMO
Giant cell carcinoma, a rare variant of nonsmall cell lung carcinoma (NSCLC), is characterized by aggressive progression and poor response to conventional chemotherapy. This report is the first to describe a patient with NSCLC and giant cell features who was successfully treated with pembrolizumab, an antibody targeting programmed death-1 (PD-1). A 69-year-old woman was diagnosed with NSCLC with multiple brain metastases. Histological evaluation of lung biopsy specimens revealed proliferation of pleomorphic giant tumor cells with poor cohesiveness, findings consistent with giant cell carcinoma. Immunostaining showed that a high proportion of the tumor cells were positive for expression of programmed death-ligand 1 (PD-L1). The patient received stereotactic radiotherapy for the brain metastases, followed by administration of pembrolizumab. Treatment with pembrolizumab resulted in the rapid regression of the primary lung nodule, with the progression-free period maintained for at least four treatment cycles. Immunotherapy targeting PD-1/PD-L1 may be an option for patients with PD-L1-positive NSCLC with giant cell features.
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A 59-year-old woman was referred to our hospital with the finding of an incidentaloma in her right kidney. Computed tomographyand magnetic resonance imaging showed a solid tumor, approximately8 cm in diameter, at the lower pole of the right kidney. Partial nephrectomy was performed without a renal vessel clamp. Histopathologically, fibroblast-like spindle cells were proliferating with rich collagenous fibers, and tumor cells were infiltrated into the renal parenchyma. The tumor cells were stained positive with CD34, CD99, and bcl-2. The tumor was diagnosed as solitaryfibrous tumor originating from the kidney based on these histopathological findings. The patient was followed 3 years after surgery with neither recurrence nor metastasis.
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Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Tumores Fibrosos Solitários/diagnóstico por imagem , Feminino , Humanos , Neoplasias Renais/cirurgia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Imagem Multimodal , Nefrectomia , Tumores Fibrosos Solitários/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Low-grade cribriform cystadenocarcinoma (LGCCC) is a recently described rare tumor of the salivary gland; this tumor most frequently arises from the parotid gland. Here, we describe a case of LGCCC arising from a minor salivary gland in the buccal mucosa. A 72-year-old man had a small mass on the left buccal mucosa. The mass was completely resected, and the postoperative course was uneventful. Histopathologically, the tumor comprised a single cyst with intraductal proliferation. Based on these histopathological findings along with immunohistochemistry a diagnosis of LGCCC arising from a minor salivary gland was made. (J Oral Sci 58, 145-149, 2016).
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Cistadenocarcinoma/diagnóstico , Neoplasias das Glândulas Salivares/diagnóstico , Idoso , Cistadenocarcinoma/patologia , Humanos , Masculino , Neoplasias das Glândulas Salivares/patologiaRESUMO
Transformation of human embryonic stem cells (hESC) is of interest to scientists who use them as a raw material for cell-processed therapeutic products. However, the WHO and ICH guidelines provide only study design advice and general principles for tumorigenicity tests. In this study, we performed in vivo tumorigenicity tests (teratoma formation) and genome-wide sequencing analysis of undifferentiated hESCs i.e. SEES-1, -2 and -3 cells. We followed up with teratoma formation histopathologically after subcutaneous injection of SEES cells into immunodeficient mice in a qualitative manner and investigated the transforming potential of the teratomas. Maturity of SEES-teratomas perceptibly increased after long-term implantation, while areas of each tissue component remained unchanged. We found neither atypical cells/structures nor cancer in the teratomas even after long-term implantation. The teratomas generated by SEES cells matured histologically over time and did not increase in size. We also analyzed genomic structures and sequences of SEES cells during cultivation by SNP bead arrays and next-generation sequencing, respectively. The nucleotide substitution rate was 3.1 × 10-9, 4.0 × 10-9, and 4.6 × 10-9 per each division in SEES-1, SEES-2, and SEES-3 cells, respectively. Heterozygous single-nucleotide variations were detected, but no significant homologous mutations were found. Taken together, these results imply that SEES-1, -2, and -3 cells do not exhibit in vivo transformation and in vitro genomic instability.
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Solitary fibrous tumor is a rare mesenchymal neoplasm, characterized by peculiar histological features composed by the proliferation of spindle cells in "patternless pattern". Although it has been known to sometimes be accompanied by epithelioid cells, the presence of a well-formed epithelial structure is far more rare. We describe herein the case of a 60-year-old female with the radiological finding of a single nodular lesion in the anterior mediastinum. Histopathological examination of the surgically resected specimen led to the diagnosis of solitary fibrous tumor of the thymus with a spectrum of well-formed epithelial components: i) glandular structure, reminiscent of breast or eccrine gland, ii) neural tube-like structure, and iii) clusters of endocrine-like cells. Immunohistochemical analysis revealed that the spindle cells expressed CD34, vimentin, bcl-2 and Stat-6, but not keratin (cytokeratin-AE1/AE3) or epithelial membrane antigen. In contrast, the epithelial components lost expression of most of these marker proteins, including Stat-6, but continued to express vimentin and strongly expressed keratin. Since no relevant past literature was found, the current case could be interpreted as a unique and previously undescribed variant of solitary fibrous tumor comprising conventional spindle cells with a spectrum of well-formed epithelial components. Pathogenesis that may have given rise to these variegated mixtures of spindle cells and epithelial components in a single tumor is also discussed.
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Biomarcadores Tumorais/metabolismo , Tumores Fibrosos Solitários/patologia , Neoplasias do Timo/patologia , Vimentina/metabolismo , Antígenos CD34/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Humanos , Imuno-Histoquímica , Queratinas/metabolismo , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição STAT6/metabolismo , Tumores Fibrosos Solitários/metabolismo , Tumores Fibrosos Solitários/cirurgia , Fuso Acromático/metabolismo , Neoplasias do Timo/metabolismo , Neoplasias do Timo/cirurgiaRESUMO
â¢We present a case of female adnexal tumor of probable Wolffian origin progressed rapidly while it is classified in LPM.â¢This case suggests that recurrence can occur within 1 year in patients with tumor implants at initial surgery.
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We report an atypical case of non-sebaceous lymphadenoma (NSL) of the parotid gland showing serous acinic cell differentiation. NSL is a rare benign salivary gland tumor with intermingled lymphoid and epithelial tissues without sebaceous differentiation. Since the first description of a case designated by Auclair et al. as 'non-sebaceous lymphadenoma' in 1991, to our best knowledge, only 37 cases have been reported, and no differentiation of tumor cells into serous acinic cell lineage has been described so far. In this paper, we present a case of NSL with serous acinic cell differentiation. The patient was a 78-year-old female with the complaint of a painless mass in the left parotid gland. The surgically resected tumor was encapsulated and measured 13 × 9 × 9 mm. Histologically, the tumor had the features of NSL, and an unusual finding of this case was the presence of epithelial cells with serous acinic cell differentiation. Dense cytoplasm packed with basophilic granules in those cells was positive in periodic acid Schiff reaction after diastase digestion (D-PAS), which was compatible with the feature of serous acinic cell differentiation. Possible differentiation of the epithelial component into serous acinic cell in this rare entity is warranted to avoid confusion in the diagnosis.
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Células Acinares/patologia , Biomarcadores Tumorais/metabolismo , Linfoma/patologia , Glândula Parótida/patologia , Neoplasias Parotídeas/patologia , Células Acinares/fisiologia , Idoso , Feminino , Humanos , Linfoma/diagnóstico por imagem , Linfoma/cirurgia , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/cirurgia , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/cirurgia , Radiografia , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: The effect of polaprezinc, a zinc-carnosine chelate compound, on the development of non-alcoholic steatohepatitis (NASH) was investigated in dietary methionine and choline deficient (MCD) mice. METHODS: Mice were fed the MCD diet with or without polaprezinc (2.2 g/kg diet) for 10 weeks. Liver histopathology, triglyceride and lipid peroxide levels, and the expression of genes linked to fibrosis were then assessed. RESULTS: MCD mice developed steatohepatitis accompanied by mild fibrosis with an increase in lipid peroxidation, hepatic stellate cell (HSC) activation, and the augmented mRNA expression of tumor necrosis factor-alpha, transforming growth factor-beta1 and procollagen alpha1(I). The mRNA expression levels of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were also enhanced. Histopathologically, polaprezinc supplementation did not influence the development of steatosis but it apparently attenuated fibrosis. Polaprezinc slightly reduced lipid peroxidation and suppressed HSC activation as well as the mRNA expression of pro-inflammatory cytokines. Polaprezinc affected the MCD diet-enhanced expression of TIMP-1 even when administered relatively late. CONCLUSION: These results suggest that polaprezinc attenuates fibrosis in NASH by reducing inflammation and lipid peroxidation and, during a later phase, promoting fibrolysis via the inhibition of TIMP expression in the liver. Further investigation is required to clarify the clinical efficacy of polaprezinc in patients with NASH.
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Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Carnosina/análogos & derivados , Fígado Gorduroso/tratamento farmacológico , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Alanina Transaminase/sangue , Animais , Peso Corporal/efeitos dos fármacos , Carnosina/farmacologia , Deficiência de Colina/complicações , Deficiência de Colina/tratamento farmacológico , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Modelos Animais de Doenças , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metionina/deficiência , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Fatores de Tempo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Compostos de Zinco/farmacologiaRESUMO
We present an extraordinarily rare finding of a testicular seminoma apparently in the process of spontaneous regression without accompanying metastatic lesion. A 35-year-old man visited our institute for persistent scrotal induration after the administration of antibiotics for several weeks. Ultrasonography and magnetic resonance imaging showed a capsulized tumor in his left atrophic testicle, without other visceral tumor or lymphadenopathy. We performed left radical orchiectomy. Histological examination revealed a fibrotic tumor with a small area of pure seminoma apparently undergoing spontaneous regression, and an intratubular germ cell neoplasia, unclassified, occurring diffusely. The patient is free of disease at 1 year after surgery.