[A case of primary central nervous system lymphoma of the sellar region presented with panhypopituitarism].

The patient is a 41-year-old woman. She presented with vomiting and lightheadedness, and blood tests showed a generalized decrease in pituitary hormones and hyperprolactinemia. A head MRI showed increased signal intensity lesions on FLAIR image in the pituitary stalk, corpus callosum, periventricular area of the fourth ventricle, and superior cerebellar peduncle. The lesions were homogeneously enhanced, and a brain biopsy confirmed the diagnosis of primary diffuse large B-cell lymphoma of the central nervous system, and chemotherapy was started. Although the suprasellar region is a rare site for primary central nervous system lymphoma (PCNSL), it should be diagnosed early by biopsy.

Carcinomatous Meningitis and Hydrocephalus in Plasmacytoid Urothelial Carcinoma of the Urinary Bladder With Extremely Elevated CA19-9 Levels.

This case report describes a rare and aggressive presentation of plasmacytoid urothelial carcinoma (PUC) with carcinomatous meningitis, hydrocephalus, extensive organ involvement, and extremely elevated serum CA19-9 levels. Autopsy findings revealed that PUC of the urinary bladder origin caused carcinomatous meningitis and hydrocephalus, with exacerbation of hydrocephalus as the direct cause of death. Immunohistochemical studies confirmed the bladder origin of PUC, and PUC cells were positive for CA19-9, a tumor marker commonly associated with gastrointestinal malignancies, suggesting that the markedly high serum CA19-9 level was related to the tumor-producing mechanism.

[A case of caseous calcification of mitral annulus resulting in multiple cerebral infarctions].

The patient is a 73-year-old woman. She presented with dysarthria, and a head MRI revealed multiple acute cerebral infarctions in the bilateral cerebral hemisphere and cerebellar hemisphere. Transesophageal echocardiography after admission revealed a 16 mm large mobile calcification of the mitral annulus (caseous calcification of the mitral annulus; CCMA) on the posterior apex of the mitral valve annulus. Since the CCMA had a high risk of relapse, and a new infarction was detected on the 8th day, resection of the mass and mitral valve replacement surgery were performed. CCMA is a subtype of mitral annular calcification (MAC). When calcification progresses from the MAC state to form a mass, it is called a calcified amorphous tumor; CAT. Reports of embolic cerebral infarction caused by CAT are rare, but this is a rare report of an embolic cerebral infarction from CCMA presenting as CAT.

Paraneoplastic Polymyositis Due to Renal Cell Carcinoma in a Patient with Autosomal Dominant Polycystic Kidney Disease.

We herein report a 70-year-old man with malaise and muscle weakness that had developed within a month. The patient also had abdominal fullness due to polycystic kidney disease. Severe proximal skeletal muscle weakness and mild elevation of creatinine kinase to 301 IU/L were noted. A muscle biopsy of the right bicep showed polymyositis. Computed tomography showed a right renal mass, and an analysis after right nephrectomy identified clear cell carcinoma. The muscle weakness subsided one month after nephrectomy and intravenous immunoglobulin therapy. Therefore, we suspect that the development of polymyositis in this patient was closely related to renal cell carcinoma.

Pembrolizumab on pre-existing inclusion body myositis: a case report.

BACKGROUND: Cases of exacerbation of pre-existing neuromuscular diseases induced by immune checkpoint inhibitors (ICIs) have rarely been reported because patients with autoimmune diseases have generally been excluded from ICI therapy due to the increased risk of exacerbation. We describe the first case of an elderly patient who experienced exacerbation of a previously undiagnosed sporadic inclusion body myositis (sIBM), the most common myopathy in the geriatric population, which was triggered by anti-programmed cell death-1 therapy. CASE PRESENTATION: A 75-year-old man who was receiving pembrolizumab presented with limb weakness. Three years prior, he had noticed slowly progressive limb weakness, but he received no diagnosis. After the first infusion of pembrolizumab, his creatine kinase (CK) levels had increased. The neurological examination and muscle biopsy findings confirmed the diagnosis of sIBM and suggested exacerbation of sIBM induced by pembrolizumab. After the patient's CK levels decreased, pembrolizumab was restarted. The tumor progressed after its treatment with pembrolizumab. The patient died after 15 months of follow-up. CONCLUSIONS: In patients with slowly progressive limb weakness, sIBM should be explored before ICI therapy. In addition, if patients show high CK levels after ICI introduction, it is necessary to confirm whether they have sIBM in order to avoid unnecessary immunosuppressive therapies and assess whether they can tolerate ICI reintroduction.

Ramsay-Hunt syndrome and subsequent sensory neuropathy as potential immune-related adverse events of nivolumab: a case report.

BACKGROUND: Nivolumab is an immune checkpoint inhibitor (ICI) and is used for the treatment of advanced non-small cell lung cancer (NSCLC). Several immune-mediated neurological adverse events associated with ICIs have been reported to date, such as Guillain-Barré syndrome. Nivolumab-associated neurological adverse events can vary, and their etiology remains unclear. CASE PRESENTATION: A 72-year-old man with NSCLC was treated with nivolumab as a second-line therapy. After 13 rounds of nivolumab therapy, he presented with Ramsay-Hunt syndrome (RHS) followed by acute ataxic sensory neuropathy. Antiviral therapy for Varicella-Zoster virus and prednisolone resulted in partial improvement of RHS, while almost no recovery was observed in the sensory neuropathy. However, the sensory ataxia significantly improved after intravenous immunoglobulin (IVIg) therapy, and interestingly, the facial palsy associated with RHS also improved. The neurological manifestations, nerve conduction study result, and imaging findings supported that dorsal root ganglia were the primary lesion site of acute ataxic sensory neuropathy. CONCLUSIONS: Our case presented with the comorbidity of RHS and subsequent ataxic sensory neuropathy after nivolumab therapy to whom IVIg was effective. Our case suggested the wide variability of possible neurological symptoms, and the potential usefulness of IVIg to sensory ataxic neuropathy, seen in cancer patients with ICI treatment.

Cancer association as a risk factor for anti-HMGCR antibody-positive myopathy.

OBJECTIVE: To show cancer association is a risk factor other than statin exposure for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase autoantibody-positive (anti-HMGCR Ab+) myopathy. METHODS: We analyzed the clinical features and courses of 33 patients (23 female and 10 male) with anti-HMGCR Ab+ myopathy among 621 consecutive patients with idiopathic inflammatory myopathies. RESULTS: Among the 33 patients, 7 (21%) were statin-exposed and 26 were statin-naive. In relation with cancer, there were 12 patients (statin-exposed, n = 4) with cancers detected within 3 years of myopathy diagnosis (cancer association), 3 patients (all statin-naive) with cancers detected more than 3 years before myopathy diagnosis (cancer history), 10 cancer-free patients followed up for more than 3 years (all statin-naive), and 8 patients without cancer detection but followed up for less than 3 years (statin-exposed, n = 3). Therefore, 12 patients with cancer association (36%) formed a larger group than that of 7 statin-exposed patients (21%). Among 12 patients with cancer association, 92% had cancer detection within 1 year of myopathy diagnosis (after 1.3 years in the remaining patient), 83% had advanced cancers, and 75% died of cancers within 2.7 years. Of interest, 1 patient with cancer history had sustained increase in creatine kinase level over 12 years from cancer removal to the development of weakness. CONCLUSIONS: Patients with cancer association formed a large group with poor prognosis in our series of patients with anti-HMGCR Ab+ myopathy. The close synchronous occurrence of cancers and myopathies suggested that cancer association is one of the risk factors for developing anti-HMGCR Ab+ myopathy.

Anti-TIF1-γ antibody and cancer-associated myositis: A clinicohistopathologic study.

OBJECTIVE: We aimed to analyze the clinical and histopathologic features of cancer-associated myositis (CAM) in relation to anti-transcriptional intermediary factor 1 γ antibody (anti-TIF1-γ-Ab), a marker of cancer association. METHODS: We retrospectively studied 349 patients with idiopathic inflammatory myopathies (IIMs), including 284 patients with pretreatment biopsy samples available. For the classification of IIMs, the European Neuromuscular Center criteria were applied. Patients with CAM with (anti-TIF1-γ-Ab[+] CAM) and without anti-TIF1-γ-Ab (anti-TIF1-γ-Ab[-] CAM) were compared with patients with IIM without cancers within and beyond 3 years of myositis diagnosis. RESULTS: Cancer was detected in 75 patients, of whom 36 (48%) were positive for anti-TIF1-γ-Ab. In anti-TIF1-γ-Ab(+) patients with CAM, cancers were detected within 1 year of myositis diagnosis in 35 (97%) and before 1 year of myositis diagnosis in 1. All the anti-TIF1-γ-Ab(+) patients with CAM satisfied the dermatomyositis (DM) criteria, including 2 possible DM sine dermatitis cases, and were characterized histologically by the presence of perifascicular atrophy, vacuolated fibers (VFs), and dense C5b-9 deposits on capillaries (dC5b-9). In contrast, 39 anti-TIF1-γ-Ab(-) patients with CAM were classified into various subgroups, and characterized by a higher frequency of necrotizing autoimmune myopathy (NAM). Notably, all 7 patients with CAM classified into the NAM subgroup were anti-TIF1-γ-Ab(-) and exhibited no dC5b-9 or VFs. CONCLUSIONS: CAM includes clinicohistopathologically heterogeneous disease entities. Among CAM entities, anti-TIF1-γ-Ab(+) CAM has characteristically shown a close temporal association with cancer detection and the histopathologic findings of dC5b-9 and VFs, and CAM with NAM is a subset of anti-TIF1-γ-Ab(-) CAM.

Sporadic late-onset nemaline myopathy as a rare cause of slowly progressive muscle weakness with young adult onset.

INTRODUCTION: Sporadic late-onset nemaline myopathy (SLONM) is a rare intractable acquired myopathy characterized by progressive muscle weakness and atrophy, usually with middle to late adult onset. Autologous peripheral blood stem cell transplantation (auto-PBSCT) has been reported to be a promising treatment for SLONM. METHODS: In this study we performed clinical characterization, muscle histopathological analysis, and muscle power monitoring after auto-PBSCT in a 27-year-old HIV-negative man with monoclonal gammopathy. RESULTS: He showed improved muscle strength after treatment with high-dose melphalan and auto-PBSCT. CONCLUSIONS: Considering the recent reports of successful treatment of SLONM, early and correct diagnosis of this condition in association with monoclonal gammopathy is important. SLONM should be added to the list of diseases to consider in the differential diagnosis of progressive muscle weakness with young adult onset.

[A 34-year-old woman with cat scratch disease who developed encephalopathy].

We experienced a patient with cat-scratch disease (CSD) who developed encephalopathy. The subject was a 34-year-old female who had been aware of a low-grade fever and swollen inguinal lymph nodes for 1 month. The subject's consciousness became impaired after a headache developed, accompanied by fever, nausea, and vomiting, and she subsequently sought medical consultation. No major abnormalities were observed in the cerebrospinal fluid and cranial magnetic resonance imaging (MRI) was normal. However, necrotizing lymphadenitis was observed on contrast enhanced computed tomography (CT) of the pelvis and granulomatous changes were observed in a surgical lymph node biopsy. As the subject lived with a pet cat, PCR testing for Bartonella henselae (the CSD pathogen) was performed using a tissue biopsy. This was positive and the subject was diagnosed with CSD encephalopathy. There are very few domestic reports of CSD encephalopathy and care must be taken not to overlook this disease.

[Case of primary intraocular central nervous system lymphoma with high interleukin 10 level and positive cytology in cerebrospinal fluid].

A 73-year-old woman was admitted to the surgical department of our hospital for endoscopic resection of a colonic polyp. The day after endoscopic resection, she became drowsy and dysphasic. Two days later, left hemiparesis and gait difficulty developed. The next day, hemiparesis progressed bilaterally and dyspnea developed due to upper airway stenosis. The most prominent signs were those of bulbar palsy. Blood analysis revealed mild inflammatory responses and hyponatremia. T2-weighted magnetic resonance imaging showed high-intensity lesions in the swollen medulla and cervical spinal cord. Those areas and the meninges of the posterior fossa were enhanced by gadolinium. Steroid pulse therapy was administered, resulting in rapid recovery of bulbar and paretic symptoms with decreased enhanced area. At this point, concentration of cerebrospinal fluid interleukin (IL)-10 was markedly elevated at 146 pg/ml (normal,< 5 pg/ml), suggesting malignant lymphoma. Cytology of the cerebrospinal fluid was repeatedly examined, eventually revealing atypical lymphocytes with hyperlobulated nuclei and clear nucleoli. Lymphocytes stained with anti-CD20 antibody. These findings strongly suggested a diagnosis of primary intraocular and central nervous system lymphoma. In the present case, repeated cytology of cerebrospinal fluid was highly important for diagnosis in this case of high IL-10 level in cerebrospinal fluid.

[The painful multiple mononeuropathy of acute onset in the left arm which was diagnosed as leprous neuropathy].

A 31-year-old man from Myanmar with leprous neuropathy was reported. The progress of the disease was subacute but the painful symptom at the time of the onset was acute. Multiple mononeuropathy was diagnosed by the biopsy findings of the left superficial radial nerve. He was admitted to our hospital with the complaint of the weakness of his left hand and fingers which were very painful and got worse in several weeks. Motor palsy was observed in his left ulnar, median, and radial nerves, and there was the hypesthesia or anesthesia in his left hand, forearm and the medial side of his left upper arm. On nerve conduction studies, the amplitudes of CMAP and SNAP severely diminished or not detected. The pattern was compatible with multiple mononeuropathy. The biopsy of the left superficial radial nerve was performed. The pathological findings were the destruction of nerve fascicles, replacement of nerve fibers with inflammatory cells, and Mycobacterium leprae was found with the specific stain. These findings confirmed the diagnosis of the leprous neuropathy. Leprous neuropathy is one of the commonest causes of infectious neuropathy in the world, especially in Southeast Asia. These days many foreign workers from that area are staying in Japan, and the chances to see the disease are increasing. We have to recognize leprous neuropathy as a candidate for the multiple mononeuropathy of acute onset with painful dysesthesia similar to vascular neuropathy.