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The development of next-generation sequencing (NGS) has enabled the discovery of cancer-specific driver gene alternations, making precision medicine possible. However, accurate genetic testing requires a sufficient amount of tumor cells in the specimen. The evaluation of tumor content ratio (TCR) from hematoxylin and eosin (H&E)-stained images has been found to vary between pathologists, making it an important challenge to obtain an accurate TCR. In this study, three pathologists exhaustively labeled all cells in 41 regions from 41 lung cancer cases as either tumor, non-tumor or indistinguishable, thus establishing a "gold standard" TCR. We then compared the accuracy of the TCR estimated by 13 pathologists based on visual assessment and the TCR calculated by an AI model that we have developed. It is a compact and fast model that follows a fully convolutional neural network architecture and produces cell detection maps which can be efficiently post-processed to obtain tumor and non-tumor cell counts from which TCR is calculated. Its raw cell detection accuracy is 92% while its classification accuracy is 84%. The results show that the error between the gold standard TCR and the AI calculation was significantly smaller than that between the gold standard TCR and the pathologist's visual assessment (p<0.05). Additionally, the robustness of AI models across institutions is a key issue and we demonstrate that the variation in AI was smaller than that in the average of pathologists when evaluated by institution. These findings suggest that the accuracy of tumor cellularity assessments in clinical workflows is significantly improved by the introduction of robust AI models, leading to more efficient genetic testing and ultimately to better patient outcomes.
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BACKGROUND: Unlike the already established effect of Helicobacter pylori (H. pylori) eradication on gastric mucosa-associated lymphoid tissue (MALT) lymphoma, its therapeutic effect on primary gastric diffuse large B-cell lymphoma (DLBCL) is still unclear. AIM: To clarify the efficacy of H. pylori eradication treatment for primary gastric DLBCL. METHODS: We reported on 3 new cases, and added them to 3 previously reported cases. We analyzed the usefulness of H. pylori eradication treatment for gastric DLBCL for a total of 6 cases at our center. RESULTS: Of the 6 patients (27-90 years old, 3 males and 3 females), all 3 patients with single lesions (one transformed from MALT lymphoma) achieved complete remission (CR) after H. pylori eradication. Regarding the 2 newly reported cases, CR was maintained for more than 6 years with eradication treatment alone. In contrast, none of the 3 patients with 2 lesions achieved CR. In 1 newly reported case, endoscopic CR was achieved in one lesion, while stable disease was obtained in the other lesion. Two patients with progressive disease responded to standard chemotherapy ± radiation and remained in CR for more than 6 years. CONCLUSION: We believe it is worthwhile to attempt H. pylori eradication for elderly patients with primary gastric DLBCL in a single lesion with a small tumor burden.
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Patients with Sjögren syndrome (SS) have a higher risk of developing malignant lymphoma.1A 68-year-old woman presented with a 2-month history of swollen parotid glands. The patient had psoriatic arthritis and had been treated with secukinumab for 3 months.
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Hodgkin lymphoma type of Richter syndrome (HL-type RS) is a rare disease that arises in patients with chronic lymphocytic leukemia (CLL). HL-type RS lesions can manifest in various sites and are often accompanied by related symptoms. This is the first case report to describe diagnosis of HL-type RS after emergency surgery for gastrointestinal perforation caused by the development of a HL-type RS lesion. A 47-year-old man diagnosed with CLL three years prior began treatment with ibrutinib due to worsening anemia and splenomegaly two months prior to the emergency department presentation. Although splenomegaly improved, lymphocytopenia, anemia, and a newly arising mesenteric lymphadenopathy continued to worsen. He presented to the emergency department with abdominal pain, and subsequent surgery revealed small intestinal perforation and mesenteric lymphadenopathy with HL-type RS confirmed by histopathological examination of the resected small intestine. He subsequently received brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A + AVD), which effectively managed the HL-type RS. If CLL clinical presentation deviates from the typical course, an early tissue biopsy should be considered to evaluate for HL-type RS. Given the adoption of the A + AVD regimen as the standard treatment for Hodgkin lymphoma, further research is needed to evaluate its efficacy in HL-type RS.
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Anemia , Doença de Hodgkin , Perfuração Intestinal , Leucemia Linfocítica Crônica de Células B , Linfadenopatia , Linfoma Difuso de Grandes Células B , Humanos , Masculino , Pessoa de Meia-Idade , Anemia/complicações , Protocolos de Quimioterapia Combinada Antineoplásica , Doença de Hodgkin/complicações , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/tratamento farmacológico , Perfuração Intestinal/etiologia , Perfuração Intestinal/complicações , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfadenopatia/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Esplenomegalia/complicaçõesRESUMO
BACKGROUND: Medulloblastomas, with four molecular subgroups, are generally rapid-growing tumors with significant contrast enhancement and well-defined margins. However, each subgroup's clinical features, including disease time course and imaging characteristics, are not well defined. OBSERVATIONS: The authors describe the case of a 15-year-old female who presented with a 7-month history of impaired left-hand movement and was found to have a lesion on the dorsal side of the fourth ventricle. T2-weighted magnetic resonance imaging (MRI) at the patient's first presentation showed diffuse hyperintense signal without apparent mass, and gadolinium-enhanced T1-weighted imaging showed very slight contrast enhancement. In 1 month, her symptoms progressed, and follow-up MRI revealed an increase in the size of the lesion, showing greater diffusion restriction and contrast enhancement. She underwent gross-total resection, and pathology was consistent with classic medulloblastoma. Genetic analysis of the tumor confirmed the wingless (WNT) molecular subgroup. Adjuvant chemotherapy and proton beam therapy were performed. At the 18-month follow-up, MRI showed no recurrence of disease. LESSONS: Slow-growing medulloblastoma is very rare and not known to be associated with a specific molecular subgroup. Here, the authors report a case of slow-growing WNT medulloblastoma, indicating that slow growth may be a feature of this subgroup.
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We present a case of breast angiosarcoma. Although B-mode ultrasonography did not indicate a tumor, contrast-enhanced ultrasonography (CEUS) was successfully delineated it. CEUS helped identify the tumor and its extent.
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Neoplasias da Mama , Hemangiossarcoma , Humanos , Feminino , Meios de Contraste , Ultrassonografia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Hemangiossarcoma/diagnóstico por imagemRESUMO
BACKGROUND: The efficacy of pre-operative systemic treatment (PST) combined with immune checkpoint inhibition (ICI) for triple-negative breast cancer (TNBC) has been recognized recently as being independent of the degree of programmed death ligand-1 (PD-L1) positivity of infiltrating immune cells, especially for patients with axillary lymph node metastasis (ALNM). METHODS: TNBC patients with ALNM were treated surgically between 2002 and 2016 in our facility (n = 109), of whom 38 received PST before resection. The presence of tumor-infiltrating lymphocytes (TILs) expressing CD3, CD8, CD68, PD-L1 (detected by antibody SP142) and FOXP3 at primary and metastatic LN sites was quantified. RESULTS: The size of invasive tumor and the number of metastatic axillary LN were confirmed as prognostic markers. The numbers of both CD8+ and FOXP3+ TILs at primary sites were also recognized as prognostic markers, especially for overall survival (OS) (CD8, p = 0.026; FOXP3, p < 0.001). The presence of CD8+, FOXP3+ and PD-L1+ cells was better maintained in LN after PST and may contribute to improved antitumor immunity. Provided they were present as clusters of ≥ 70 positive cells, even < 1% of immune cells expressing PD-L1 at primary sites predicted a more favorable prognosis for both disease-free survival (DFS) (p = 0.004) and OS (p = 0.020). This was the case not only for 30 matched surgical patients, but also in all 71 surgical only patients (DFS: p < 0.001 and OS: p = 0.002). CONCLUSIONS: PD-L1+ , CD8+ or FOXP3+ immune cells in the tumor microenvironment (TME) at both primary and metastatic sites are significant on prognosis, which could be a clue to expect the potential for better responses to the combination of chemotherapy and ICI, especially for patients with ALNM.
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Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/cirurgia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Prognóstico , Metástase Linfática/patologia , Linfonodos/patologia , Fatores de Transcrição Forkhead , Linfócitos do Interstício Tumoral , Microambiente Tumoral , Biomarcadores TumoraisRESUMO
Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.
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Astrocitoma , Neoplasias Encefálicas , Encondromatose , Glioma , Oligodendroglioma , Feminino , Humanos , Adulto Jovem , Adulto , Oligodendroglioma/genética , Oligodendroglioma/patologia , Encondromatose/complicações , Encondromatose/genética , Encondromatose/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Hibridização in Situ Fluorescente , Isocitrato Desidrogenase/genética , Glioma/genética , Astrocitoma/genética , Astrocitoma/patologia , MutaçãoRESUMO
INTRODUCTION: We report a rare case of primary renal leiomyosarcoma with a tumor thrombus in the inferior vena cava. CASE PRESENTATION: A 54-year-old woman presented with right flank pain and abdominal distension. Physical examination findings were unremarkable. Abdominal computed tomography revealed a heterogeneously enhancing right solid renal mass with a thrombus in the renal vein extending into the inferior vena cava. Magnetic resonance imaging demonstrated a renal tumor with a thrombus about 4 cm below the hepatic vein. Chest computed tomography and bone scintigraphy were negative. The patient underwent right radical nephrectomy and vena cava thrombectomy. Histophathologic evaluation of the resected tumor confirmed the diagnosis of leiomyosarcoma. She underwent no adjuvant therapy. Seven months after surgery, the patient died following a 2-month history of multiple pulmonary and hepatic metastases. CONCLUSION: This report highlights the importance of considering the possibility of renal leiomyosarcoma invasion to the inferior vena cava, similar to renal cell carcinoma.
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INTRODUCTION: Bone metastases confined to the posterior elements of the spine are rarely treated, as there exist no established radical surgical treatment options for this area. Herein, we present a case report of and technical note on a patient who underwent radical resection for a metastatic tumor in the thoracic spinous process. CASE PRESENTATION: A 34-year-old male presented with a nasopharyngeal carcinoma with a solitary metastatic focus in the spinous process of the 10th thoracic vertebra. Imaging revealed that the tumor was confined to the spinous process and the surrounding soft tissues. No tumor was noted in the pedicles, vertebral body, and cortical bone on the ventral side of the lamina, as well as within the spinal canal. As treatment for this solitary metastatic lesion, we decided to perform radical resection with sufficient margins that would include the involved spinous process and all surrounding soft tissues exhibiting evidence of tumor infiltration. The posterior elements of the 9th-11th vertebrae, multifidus muscles, and skin were widely resected en bloc using a T-saw. The posterior elements of the spinal column were resected at the level of pedicles without full visualization of the involved dural sac. The tumor-infiltrated soft tissues surrounding the T10 vertebral spinous process were excised without full visualization of the tumor. Adjuvant therapy was not administered postoperatively. During the second year of follow-up, no signs of recurrence or metastasis were noted. DISCUSSION: Our proposed technique allows wide resection of a solitary focus of metastasis in the posterior elements of the spine.
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Neoplasias da Coluna Vertebral , Adulto , Humanos , Masculino , Canal Medular , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgiaRESUMO
PURPOSE: To explore the clinical significance of anti-rabphillin-3A antibody for the differential diagnosis of lymphocytic panhypophysitis. METHODS AND RESULTS: A 58-year-old Japanese man developed uveitis of unknown cause in 2017. In 2019, he became aware of polyuria. In August 2020, he noticed transient diplopia and was diagnosed with right abducens nerve palsy. At the same time, he complained of fatigue and loss of appetite. Head magnetic resonance imaging demonstrated enlargement of the pituitary stalk and pituitary gland, corresponding to hypophysitis. Hormone stimulation tests showed blunted responses with respect to all anterior pituitary hormones. Central diabetes insipidus was diagnosed on the basis of a hypertonic saline loading test. Taking these findings together, a diagnosis of panhypopituitarism was made. Computed tomography showed enlargement of hilar lymph nodes. Biopsies of the hilar lymph nodes revealed non-caseating epithelioid cell granulomas that were consistent with sarcoidosis. Biopsy of the anterior pituitary revealed mild lymphocyte infiltration in the absence of IgG4-positive cells, non-caseating granulomas, or neoplasia. Western blotting revealed the presence of anti-rabphilin-3A antibody, supporting a diagnosis of lymphocytic panhypophysitis. Because the patient had no visual impairment or severe uveitis, we continued physiological hormone replacement therapy and topical steroid therapy for the uveitis. CONCLUSION: To the best of our knowledge, this is the first case of anti-rabphilin 3A antibody positive lymphocytic panhypophysitis comorbid with sarcoidosis, diagnosed by both pituitary and hilar lymph node biopsy. The utility of anti-rabphilin-3A antibody for the differential diagnosis of hypophysitis like this case should be clarified with further case studies.
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Hipofisite Autoimune , Diabetes Insípido Neurogênico , Hipopituitarismo , Sarcoidose Pulmonar , Sarcoidose , Hipofisite Autoimune/diagnóstico , Hipofisite Autoimune/tratamento farmacológico , Diabetes Insípido Neurogênico/diagnóstico , Humanos , Hipopituitarismo/diagnóstico , Masculino , Pessoa de Meia-Idade , Hipófise/patologia , Sarcoidose/complicações , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/patologiaRESUMO
Foreign body granulomas from sutures are more common among non-absorbable sutures compared to absorbable sutures and have been reported as a postoperative complication in a variety of medical fields. However, only a few cases of delayed foreign body reaction have been reported and addressed with orthopedics. We present a patient with systemic lupus erythematosus who developed an infectious suture granuloma that extended to the entire Achilles tendon and was induced by nonabsorbable sutures that were used for open Achilles tendon repair 20 years before. This granuloma was resistant to antibiotic treatment and drainage and required surgical intervention. The tumor was marginally resected, and the continuity of the Achilles tendon was preserved. Histopathological examination detected many suture materials surrounded by xanthochromic necrotic lesions and the lesion was diagnosed as a foreign body granuloma. At 1 year after the operation, the patient did not exhibit exacerbation of infection or recurrence of the tumor, and she became able to walk by herself. To the best of our knowledge, this represents the first report of an infectious delayed foreign body granuloma in autoimmune disorder patient after open Achilles tendon repair. Surgical intervention should be considered, as treatment with conservative therapy such as antibiotics may be difficult.
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Tendão do Calcâneo , Granuloma de Corpo Estranho , Procedimentos de Cirurgia Plástica , Tendão do Calcâneo/cirurgia , Feminino , Granuloma de Corpo Estranho/diagnóstico , Granuloma de Corpo Estranho/etiologia , Granuloma de Corpo Estranho/cirurgia , Humanos , Ruptura/cirurgia , Técnicas de Sutura , Suturas/efeitos adversosRESUMO
A 73-year-old woman with atrial fibrillation treated with rivaroxaban was hospitalized for nephrotic syndrome. After discontinuation of rivaroxaban to lower the risk of hemorrhagic events, a renal biopsy was performed. Rivaroxaban was scheduled to resume a week after the biopsy to prevent renal hemorrhaging. However, she developed acute brachial arterial embolic occlusion and mural thrombosis in the abdominal aorta before resuming rivaroxaban. If immune-mediated renal diseases are suspected in anticoagulated patients at a risk of thrombotic events, physicians should consider initiating glucocorticoid therapy without a renal biopsy in order to avoid hemorrhagic and thrombotic events.
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Fibrilação Atrial , Síndrome Nefrótica , Idoso , Anticoagulantes/efeitos adversos , Biópsia , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Síndrome Nefrótica/tratamento farmacológico , Rivaroxabana/efeitos adversosRESUMO
Lymphoepithelioma-like carcinoma is a poorly differentiated carcinoma with prominent lymphoid infiltration occurring in various organs but is exceedingly rare in the colorectal region. This malignancy is frequently associated with Epstein-Barr virus (EBV). Here we report a case of EBV-associated lymphoepithelioma-like carcinoma of the cecum in an 84-year-old male who presented with occult blood. In situ hybridization for EBV-encoded small RNAs (EBER) in an endoscopic submucosal dissection specimen showed that the tumor consisted of EBER-negative well-differentiated tubular adenocarcinoma and EBER-positive lymphoepithelioma-like carcinoma. Real-time PCR detected 7.16 copies of the EBV genome per cell in a sample microdissected from the latter component. Genotyping analysis demonstrated EBV genotype 1, and viral protein/transcript expression in the tumor showed EBV latency I. Expression of Ephrin receptor A2, a recently reported receptor for EBV, was demonstrated in the tumor cells by immunohistochemistry. To our knowledge, this is the first report of lymphoepithelioma-like carcinoma in the colorectal region showing a definite association with EBV infection.
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Neoplasias do Colo , Infecções por Vírus Epstein-Barr/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Idoso de 80 Anos ou mais , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Colo/patologia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia , Herpesvirus Humano 4/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , RNA Viral/análise , Receptor EphA2/análiseRESUMO
A 5-year-old girl presented with headache and vomiting. Head computed tomography and magnetic resonance imaging showed a right frontal lobe tumor with marked calcification. The patient underwent resection surgery with suspicion of anaplastic ependymoma, and the tumor was gross totally removed. Pathological examination revealed areas of dense tumor cells with a high nucleocytoplasmic ratio and myxoid areas consisting of tumor cells with a round-shaped nucleus and eosinophilic cytoplasm. Perivascular pseudorosette, necrosis, circumscribed growth, and microcalcification were also observed. Immunohistochemistry demonstrated negative staining for glial fibrillary protein and epithelial membrane antigen. Diagnosis of a high-grade neuroepithelial tumor (HGNET) with BCL6 corepressor (BCOR) alteration was made based on pathological findings and internal tandem duplication in the exon 15 of BCOR. Although calcification on radiological and pathological examination is not typical, it would be essential to recognize that calcification could appear in HGNET-BCOR.
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Neoplasias Encefálicas , Calcinose , Neoplasias Neuroepiteliomatosas , Proteínas Proto-Oncogênicas , Proteínas Repressoras , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Pré-Escolar , Proteínas Correpressoras/análise , Proteínas Correpressoras/genética , Feminino , Duplicação Gênica , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/patologia , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Radiologia , Proteínas Repressoras/análise , Proteínas Repressoras/genéticaRESUMO
While immune checkpoint inhibitors (ICIs) have antitumor effects, they also have characteristic side effects, including colitis. However, gastritis has rarely been reported. We report a case of a patient with lung adenocarcinoma who presented with epigastric pain and diarrhea following pembrolizumab administration. Sonography of the abdomen demonstrated diffuse, although mild, gastric wall thickening (mainly in the submucosa), as well as a slight decrease in echogenicity throughout the gastric wall. While the mucosal surface was relatively smooth, color Doppler examination showed increased vascularity. Esophagogastroduodenoscopy and pathological examination confirmed the diagnosis of ICI-related gastroenteritis.