Jun-ichiro Kida

Marked Hematopoiesis Masquerading Multiple Bone Metastasis in a Lung Cancer Patient With Myelodysplastic Syndrome.

We diagnosed a 62-year-old man with lung cancer, well-differentiated squamous cell carcinoma, on the right upper lobe and left lower lobe. He had a history of myelodysplastic syndrome and refractory anemia with ringed sideroblasts diagnosed 5 years earlier. The patients ¹⁸F-FDG PET/CT for the clinical staging of lung cancer revealed accumulations of FDG in multiple bones including the rib bones, which strongly suggested multiple bone metastases. He underwent lobectomies and excision of the right fourth and fifth rib bones. The pathological findings of resected rib bones exhibited hypercellular bone marrow without excess of blasts.

Neurotropic infiltration and neuropathy of multifocal lymphoma

One of the characteristics of multifocal lymphoma is an involvement of extranodal sites including peripheral nerves and the central nervous system [1]. This neurotropic manifestation as a rare type of lymphoma has been established using the term Bneurolymphomatosis^ [2], which is a distinct clinical entity affecting neural structures and the peripheral and central nervous systems. Neurolymphomatosis occurs as an infiltration of a malignancy, almost always by nonHodgkin lymphoma as diffuse large B cell lymphoma (DLBCL). Because of the neurotropic pathogenicity of neurolymphomatosis, sensorimotor neuropathy lessens the patient’s quality of life and frequently hinders the patient’s treatment course. We treated a 28-year-old Japanese woman diagnosed with DLBCL involving multiple extranodal sites including breast, ovary, skin, bones, and muscles. She had huge bilateral breast masses (10 cm dia. in both breasts) at onset (Fig. 1a). Her main lymphoma burden was in the breasts, although her case did not meet the original criteria of primary breast lymphoma (PBL) [3]. She underwent on-front salvage chemotherapy and achieved complete remission (CR) after two courses of rituximab-hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone). Autologous stem cell transplantation was planned soon after the patient achieved CR, but she complained of bilateral femoral pain and lumbago on day 19 after completion of the last chemotherapy course. Multimodal detection to identify the cause of the pain (CT scanning, MRI imaging, and FDG-PET/CT) were performed. The subtle but substantial FDG uptake revealed that her disease had recurred at multiple neural nodules including dorsal root ganglia (Fig. 1b). Concomitant cerebrospinal fluid involvement was observed. We diagnosed a relapse based on the clinical pathology of neurolymphomatosis. The patient’s pain was scarcely relieved by the administration (oral, intravenous, and transcutaneous) of various types of opioids including oxycodone, morphine, and phentanyl analgesia. Only a new salvage chemotherapy, CODOX-M/IVAC (cyclophosphamide, doxorubicin, highdose methotrexate/ifosfamide, etoposide, and high-dose cytarabine) provided a tentative remission of the pain, but the analgesic effect did not last for more than 14 days. After the patient’s neurological relapse, disease control was not obtained, and she died from multiple infections and severe hemorrhagic cystitis. An autopsy was performed as a pathological investigation to examine the etiology of the patient’s neuropathic intractable pain. The histologic examination of the patient’s para-aortic nerve revealed neural hyperplasia with no infiltration of lymphoma cells (Fig. 1c). To the best of our knowledge, neural hyperplasia associated with cancer has not been reported. Regarding the * Osamu Imataki oima@med.kagawa-u.ac.jp

Delayed flare reaction of draining vein due to subcutaneous bortezomib more likely to occur at the inner thigh

This reaction is known as a ‘bortezomib-associated rash.’ The etiology of the rash is not clearly elucidated, but the rash is histologically categorized into two groups: inflammatory infiltration composed mainly of lymphocytes, and that of neutrophils. In any case, the inflammation is induced by an indirect reaction. Another common skin reaction is injection site erythema. An injection site reaction (ISR) to subcutaneous treatment with bortezomib was reported as occurring in 51 % of administrations [1]. Although a few severe local reactions, such as ulceration or necrosis, were observed [1], the high incidence of ISRs should be kept in mind by clinicians. In addition, the rare severe reaction should be avoidable under close observation. Recent reports describe ISR as a common but mild adverse event after bortezomib treatment, sometimes with a peculiar appearance and clinical manifestations to be elucidated. Although the subcutaneous administration of bortezomib has acceptable local tolerability and local reactions consist mainly of reversible redness, undesirable effects on skin and subcutaneous tissue do occur, and contributing factors may exacerbate the common occurrence of ISR. We treated a male patient with untreated multiple myeloma who developed a peculiar rash presenting vascular erythema of a draining vein, masquerading as a flare reaction. The case was diagnosed as Bence-Jones-type multiple myeloma and classified as stage IIIB according to International Staging System (ISS) criteria. After the diagnosis, we treated the patient with subcutaneous bortezomib (1.3 mg/ m, on days 1, 4, 8, 11, 22, 25, 29, and 32) from October 2013 to July 2014. From the first cycle, he showed an injection site erythema (Fig. 1a), and the same reaction occurred in each of following cycles. The ISR was observed when the bortezomib was injected at the inside of the patient’s

Persistent Left Superior Vena Cava in Hematological Malignancy Requiring Central Venous Catheter Insertion for Intensive Chemotherapy

Persistent left superior vena cava is a congenital vascular anomaly, which is possibly arrhythmogenic and thrombogenic, rarely complicated with coronary sinus atresia. We treated a 42-year-old male with Hodgkins lymphoma requiring central venous catheter placement for intensive chemotherapy. Persistent left superior vena cava was revealed after the insertion of the central venous catheter by the radiological finding of the catheter tip cannulated into the vena cava cavity. The relationship between coronary sinus atresia and persistent left superior vena cava induced by central venous catheterization remains unclear; however, the hematologist should pay attention to the malpositioning of the central venous catheter.

Anti-CD30 Antibody-Induced Radiation Recall Reaction: A Collateral Target for Activated Lymphocytes

A 75-year-old Japanese man diagnosed with anaplastic lymphoma kinase–negative anaplastic large-cell lymphoma underwent 8 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy and subsequently received 43.2 Gy/24 fractions of involved-field radiation therapy to a mediastinum mass. He had stage IV disease: the lymphoma cell was detected in both the primary-site mediastinum and the right pleural effusion. He maintained complete remission for 5 months. Routine monitoring by FDG-PET/CT (positive emission tomography/ computed tomography) detected a sign of recurrence in the lymph nodes of his thorax, which was the center of the primary mediastinum mass. Treatment was initiated with brentuximab vedotin (BV) at 1.8 mg/kg. Then, 10 days after the administration of the third course of BV treatment in an outpatient oncology unit, the patient experienced pyrexia and visited our hospital’s emergency room. Laboratory data indicated a minor infection with mild C-reactive protein elevation (0.40 mg/dL). His chest X-ray suggested an attenuation in the right lung’s upper field (Figure 1A). Chest CT revealed ground-glass opacity in both the upper (S1+2) and lower (S6) lung fields astride the pulmonary segments (Figure 1B). The patient was admitted for the treatment of pneumonia; a transbronchial lung biopsy was performed to investigate the cause of pneumonia. No pathogenic factors were detected, including bacteria, fungus, tuberculosis, and other acid-fast bacteria. Pathological findings revealed patchy interstitial fibrosis with alternating areas of normal lung and scattered fibroblastic foci in the background of dense acellular collagen (Figure 1C). In an immunohistochemical study of biopsied lung tissue, the expression of CD30 was negative (Figure 1C). However, lymphocyte infiltration with fibrotic changes was observed. Drug-induced pneumonitis caused by the BV was suspected, and high-dose methylprednisolone 500 mg/d for 3 days, followed by predonisolone1.0 mg/kg, was administered. The patient responded to the corticosteroid therapy, and the pulmonary attenuation shadow cleared within 2 weeks. Naranjo scale assessment indicated a probable adverse drug reaction. The onset of pneumonitis was 10 and 8 months after the administration of the last CHOP course and the completion of radiation therapy, respectively. There were no other pulmonary adverse reactions 589169 AOPXXX10.1177/1060028015589169Annals of Pharmacotherapy research-article2015

An Autopsy Case of Rapidly Progressing Spindle Cell Carcinoma of the Lung Accompanied with Intratumor Hemorrhage

Patient: Male, 74 Final Diagnosis: Spindle cell carcinoma of the lung Symptoms: — Medication: Pemetrexed • carboplatin Clinical Procedure: Biopsy and autopsy Specialty: Oncology Objective: Rare disease Background: Spindle cell carcinoma (SPCC) of the lung is a subset of sarcomatoid carcinoma. Its clinical features are unclear because of its rarity. Here, we report an autopsy case of SPCC and review CT findings and chemotherapeutic regimens based on previous reports of this disease. To our knowledge, this is the first reported case of pemetrexed used to treat SPCC. Case Report: A 74-year-old Japanese male presented with dyspnea and contrast-enhanced computed tomography (CT) showed abundant left pleural effusion and a mass in lower lobe of the left lung. By the tumor biopsy, he was diagnosed for SPCC of the lung, cT3N0M1a, stage IV. The tumor was resistant to chemotherapy with carboplatin and pemetrexed, and rapidly progressed. Autopsy revealed abundant hemorrhage within the tumor, which apparently reflects a low-density area in CT. Conclusions: Present case and the accumulation of cases indicate that low-density areas in CT and rapid tumor progression may be common SPCC findings.

Transepidermal growth in disseminated Fusarium infection

Dear Editor, Disseminated Fusarium infection was previously shown to be a life-threatening systemic mycotic infection in immunocompromised patients, with the mortality rate of patients with neutropenia being approximately 80%. Skin histology studies on disseminated Fusarium have focused on the thrombosis of dermal vessels by the hyphae of Fusarium. Here, we demonstrated the transepidermal growth of disseminated Fusarium from vascular vessels and epidermal degeneration in a case of severe neutropenia with acute malignant lymphoma (AML). A 28-year-old Japanese man had been hospitalized in an oncology unit. He was diagnosed with AML and received chemotherapy with cytarabine (100 mg/m) for 7 days and idarubicin (12 mg/m) for 3 days. A painful erythematous nodule was found on his right shoulder after 1 month. He received chemotherapy with fludarabine (30 mg/m) for 5 days, cytarabine (2000 mg/m) for 5 days and idarubicin (12 mg/m) for 2 days. Severe neutropenia (zero neutrophil count) was first observed on day 5, he had a high fever (>38°C) and myalgia, and the number of cutaneous lesions increased. Common antibiotic, antifungal or antiviral drugs were not effective. C-reactive protein was 31.58 mg/dL and b-D-glucan was 16.7 pg/mL on day 10. He was referred to our dermatology department on day 11 for an evaluation and the treatment of his erythematous skin lesions. A physical examination revealed multiple 1–2-cm macules and papules and painful reddish subcutaneous nodules on his trunk and limbs (Fig. 1a). Some of these had central eschars/pustules (Fig. 1b). Histopathology showed fungal thrombosis of the dermal vessels with the extravasation of erythrocytes and epidermal ulceration (Fig. 1c,d). The prominent transepidermal growth of fungus from vascular vessels and epidermal degeneration were observed (Fig. 1e). C-reactive protein was 41.89 mg/dL and b-D-glucan was 104.3 pg/mL on day 14. Fusarium species was confirmed by a blood culture test on day 15. Although voriconazole and amphotericin B were administrated, the patient died on day 16 due to multiple organ failure. Fusarium solani was identified by comparing the nucleotide sequences of the 16S ribosomal DNA D1/D2 region with those in the GenBank database after his death. Although transepidermal elimination has been often observed in the cases of chromomycosis, it may be parasitic proliferation of fungi and/or host defense reactions. In our case, fungal elements were not actively eliminated by the host. We have demonstrated for the first time, to the best of our knowledge, the transepidermal growth of Fusarium from vascular vessels and epidermal degeneration. Because Fusarium mycotoxins induce apoptosis in epidermal keratinocytes, these histological changes may suggest the explosive growth of Fusarium and its mycotoxin-induced cell apoptosis in the epidermis of severely immunocompromised patients. We should have performed direct examination of eschars/pustule materials. In cases where transepidermal growth is prominent, it may exhibit fungal elements, which could lead to early diagnosis and early treatment. However, this has not yet been elucidated in detail, and further studies on histological changes in the epidermis due to disseminated Fusarium infection are needed.