Multiple Lymph Node Swelling Research Articles

Lymphoproliferative Disorder in an Esophageal Cancer Patient Treated with Pembrolizumab.

A 75-year-old man diagnosed with esophageal cancer and lung metastasis received a combination of fluorouracil, cisplatin, and pembrolizumab. During pembrolizumab maintenance therapy, lymphoproliferative lesions at the lips and mouth and multiple lymph node swellings appeared. Histologically, Epstein-Barr virus (EBV)-encoded RNA was positive, and EBV-DNA was detected in the blood. The patient was diagnosed with other iatrogenic immunodeficiency-associated lymph proliferative disorders (OIIA-LPDs) related to EBV activation induced by pembrolizumab. Rituximab was administered, resulting in the improvement of the OIIA-LPD. The emergence of an OIIA-LPD merits close attention in patients receiving immune checkpoint inhibitors.

Collision tumor of a papillary and follicular thyroid carcinoma: a case report

BackgroundPapillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are common differentiated thyroid cancers, but the detection of a collision tumor is an extremely rare event. Case presentationThe patient was a 69-year-old Japanese female with multiple cervical lymph node swellings and a thyroid tumor. Preoperative fine needle aspiration cytology of the enlarged lymph node revealed a cytological diagnosis of papillary thyroid carcinoma (PTC). A total thyroidectomy, right cervical dissection and paratracheal dissection were performed. Histopathological and immunohistochemical analyses of resected specimens revealed a collision tumor of PTC and FTC. Multiple metastases of papillary carcinoma were found in the dissected lymph nodes. In the PTC lesion, IHC for BRAF (V600E) was positive but negative for the FTC lesion. Genetic analyses further revealed a TERT promoter C228T mutation in PTC and a NRAS codon 61 mutation in FTC. The patient died of recurrent cancer 8 months after surgery.ConclusionsA case of a collision tumor of PTC and FTC is very rare, and even fewer cases have been subjected to genetic scrutiny. The present case was successfully diagnosed by pathological examination using immunohistochemical and genetic analyses. The TERT promoter mutation in the PTC lesion was consistent with the aggressive behavior of the cancer.

Biallelic <i>BCL6</i> rearrangements by dual t(3;14)(q27;q32) and t(3;22)(q27;q11) translocations in diffuse large B-cell lymphoma

3q27 chromosomal translocation involving the BCL6 gene is one of the most frequent forms of cytogenetic abnormality observed in B-cell lymphoma. We report a case with diffuse large B-cell lymphoma (DLBCL) presenting dual 3q27 translocations. The patient was a 71-year-old man who presented with swelling of multiple abdominal lymph nodes (LNs) and obstructive jaundice. LN biopsy exhibited dense proliferation of atypical large cells expressing CD20, MUM1/IRF4, BCL2, BCL6, and MYC, but not CD10. He was diagnosed with non-GCB/ABC type DLBCL and showed an initially good response to R-CHOP chemotherapy, but relapsed soon after the completion of therapy. Chromosomal analysis of the biopsied LN exhibited multiple abnormalities including t(3;14)(q27;q32) and t(3;22)(q27;q11). Fluorescence in situ hybridization (FISH) using BCL6 break-apart probes confirmed chromosomal breaks occurring on both BCL6 alleles. Molecular analysis revealed two independent rearrangements of BCL6, either with the IGH or the IGL gene. 3q27 breakpoints were located 1.2kb apart from each other within the first intron of BCL6, while the IGH and IGL breaks occurred at the 5' of IGHG2 and within IGLV3-1, respectively. The results suggest that biallelic BCL6 rearrangements might be a rare but recurrent genetic event in B-cell lymphoma.

Clinicopathological features of T-lymphoblastic lymphoma with Langerhans cell histiocytosis in the same lymph node

Objective: To investigate the clinicopathological features, immunophenotypes, genetics and prognosis of T-lymphocyte lymphoma/myeloid sarcoma combined with Langerhans cell histiocytyosis (coexistence of T-LBL/MS and LCH). Methods: Clinical and pathological data of the 6 patients with coexistence of T-LBL/MS and LCH were analyzed, who were diagnosed at the Foshan Hospital of Sun Yat-sen University and the Friendship Hospital of Capital Medical University, from December 2013 to April 2019. The hematoxylin and eosin stain, immunohitochemistry (EnVision) and in situ hybridization were used. Related literatures were reviewed. Results: Four patients were T-LBL combined with LCH, 1 was T-LBL/MS combined with LCH, and 1 was MS combined with LCH. There were 2 male and 4 female patients, with age ranged from 5 to 77 years old (median, 59 years old). Three patients represented with only multiple lymph node swelling. The other 3 displayed both multiple lymph node swelling, and skin/liver or spleen lesions. Lymph node structure was destroyed in 5 cases, while 3 cases had several residual atrophic follicles. Histologically, there were two types of tumor cells: one type of the abnormal lymphoid-cells exhibited small to medium-sized blast cells, typically showing a nested distribution, and these cells were mainly identified in residual follicles and paracortical areas; the other type of histiocytoid cells had a large cell size and abundant pale or dichromatic cytoplasm. Their nuclei were irregularly shaped, showing folded appearance and nuclear grooves. These cells were mainly present in marginal sinus, medullary sinus and interstitial area between follicles. Eosinophil infiltration in the background was not evident in any of the cases. The lymphoid-cells of medium size showed TdT+/CD99+/CD7+, with variable expression of CD34/MPO/CD2/CD3. Ki-67 index was mostly 30%-50%. However, the histiocytoid cells showed phenotype of CD1a+/S-100+/Langerin+/-, while CD163/CD68 were positive in some degree. These cells did not express any T or B cell markers. The Ki-67 index mostly ranged between 10%-20%. None of the cases had Epstin-Barr viral infection. Among the 6 patients, 4 patients were followed up (6-63 months, median time, 18.5 months), of whom 1 patient died of the disease and 3 patients were alive at the end of follow-up. Conclusions: T-LBL/MS combined with LCH is a rare mixed type of immature hematopoietic disease, and mainly occurs in lymph node and skin. The clinical course is overall aggressive. Therefore, it is helpful to recognize and identify the two pathologic components in the same tissue for accurate diagnosis and proper treatment.

Undifferentiated carcinoma of the oral tongue treated with cetuximab: A case report.

Undifferentiated carcinoma of the oral cavity is a rare and possibly fatal malignant neoplasm. We present here a case of undifferentiated carcinoma of the oral tongue, which responded well to chemotherapy with cisplatin, 5-fluorouracil, and cetuximab. A 59-year-old man was referred to our hospital for a large tumor of the tongue. Physical examination revealed an ulcerative tumor, approximately 50 mm in diameter, on the right edge of the tongue and swelling of multiple cervical lymph nodes; therefore, the clinical diagnosis was tongue cancer (T4aN2bM0). The histological diagnosis from a biopsy specimen was undifferentiated carcinoma; we tested the sample for human papilloma virus immunoreactivity, which was positive. The patient then underwent chemotherapy with cisplatin, 5-fluorouracil and cetuximab. The tumor's size decreased markedly after two courses of chemotherapy, but the treatment was stopped due to the patient' various mental problems and pneumonia; he died 6 months after the initial visit. Our encounter with this patient suggests that cetuximab treatment is a good option for HPV-positive undifferentiated carcinoma of the oral tongue.

Thoracoscopic esophagectomy with subcarinal lymph node dissection in the prone position for esophageal cancer with a right superior pulmonary vein anomaly: a case report

BackgroundSuperior posterior pulmonary vein anomaly in the right upper lobe (anomalous V2), which is one of the anomalies of the right superior pulmonary vein (RSPV), runs behind the right main or intermediate bronchus. Although this rarely occurs, attention should be given to this venous anomaly during thoracoscopic esophagectomy with subcarinal lymph node dissection. Here, we report a case of thoracoscopic esophagectomy with subcarinal lymph node dissection in the prone position for lower thoracic esophageal cancer with anomaly of the superior posterior pulmonary vein in the right lobe (anomalous V2).Case presentationA 61-year-old man was diagnosed as having lower esophageal cancer with swelling of multiple lymph nodes in the mediastinum and abdomen. His clinical diagnosis based on the eighth TNM classification system was cT3 N2 M0 stage IIIB. In addition, an anomalous V2 was recognized on preoperative computed tomography imaging before the operation. The vein ran behind the intermediate bronchus and drained into the RSPV located at the area of the subcarinal lymph node. We performed preoperative simulation by using virtual thoracoscopic imaging with the same view as that during operation to help us better dissect the lymph nodes. As a result, thoracoscopic esophagectomy and subcarinal lymph node dissection were performed in the prone position without injuring the anomalous V2. Severe complications did not occur in the postoperative course except for paralysis of the left recurrent laryngeal nerve. The patient was discharged on postoperative day 17.ConclusionsInjury to an anomalous V2 can cause severe hemorrhage during subcarinal lymph node dissection in esophagectomy. Preoperative simulation by using virtual thoracoscopic imaging is useful to avoid this complication in patients with an anatomical anomaly.

A case of pancreatic metastasis arising from occult lung cancer

A 57-year-old man was admitted with complaints of stiffness on the right clavicle. Imaging study revealed swelling of multiple lymph nodes and pancreatic mass, but there were no such findings in the lung. Endoscopic ultrasound-guided fine needle aspiration for mediastinum lymph node and pancreatic mass revealed a poorly differentiated adenocarcinoma. He was diagnosed of pancreatic cancer with multiple lymph node metastases. Chemoradiotherapy was conducted. Six months later, he suffered from cardiac tamponade and died. The autopsy revealed a small nodule of poorly differentiated adenocarcinoma in the lung that could not be pointed out by computed tomography. Immunohistochemistry showed that both tumors of the lung and pancreas were positive for thyroid transcription factor-1 and napsin A, which are specific markers of lung cancer. Final diagnosis was primary lung cancer with metastases to the pancreas and heart. Pancreatic metastasis from occult lung cancer is rare. Lung cancer must be suspected when carcinoma of unknown primary is detected, even in the absence of the image findings of the lung. Immunostaining is useful in determining the primary site; hence, obtaining the cancer tissue is important.

Concurrent eosinophilia and IgG4-related disease in a child: A case report and review of the literature.

The current study presents the case of a 9-year-old Chinese boy who presented with eosinophilia and elevated serum levels of immunoglobulin G4 (IgG4). A bone marrow puncture identified an elevated eosinophil rate of 23% (normal range, <5%), which indicated eosinophilia. However, gene analysis, fluorescent in situ hybridization and other examinations, including bone marrow aspiration, blood routine, auto-antibody tests and parasitic and allergens screening, contradicted a diagnosis of secondary or clonal eosinophilia. Furthermore, the patient exhibited multiple lymph node swelling and a lymph biopsy strongly indicted a pathological diagnosis of IgG4-related disease (IgG4-RD). His peripheral blood flow cytometry confirmed an elevated count of plasmablasts, which is specific to IgG4-RD. The patient responded well to therapy with prednisone and remained healthy in all follow-ups. By taking all these factors into consideration, the boy was diagnosed with IgG4-RD. It is difficult to distinguish IgG4-RD from hypereosinophilic syndrome and the potential association between the two remains unclear. However, the present case study serves as a reminder that IgG4-RD may occur in children and medical professionals should not neglect this possibility.

Secondary central nervous system lymphoma surrounding a region injured by subarachnoid hemorrhage and subsequent aneurysmal clipping.

The present case study describes a rare case of secondary central nervous system (CNS) lymphoma that infiltrated the dura and leptomeninges around the area injured by subarachnoid hemorrhage and subsequent aneurysmal clipping. Invasion of the CNS was observed by computed tomography as slurred fissures of the right parietal lobe adjacent to the surgery area. Subdural and subarachnoid enhancement overlapping the area injured by past surgical procedures was observed by contrast-enhanced magnetic resonance imaging. Surgical resection revealed B-cell lymphoma infiltrating the dura and leptomeninges surrounding the post-hemorrhagic area. The patient was subsequently diagnosed with systemic lymphoma and bone marrow invasion, and multiple lymph node swelling. To the best of our knowledge, this is the first report of malignant lymphoma involving the CNS overlapping a previously injured area.

Biopsy diagnosis of CD30-positive anaplastic large T-cell lymphoma of ileum in necrotic biopsies

CD30 (Ki-1)-positive anaplastic large cell lymphoma (ALCL) has been reported only once in ileum. A 72-year-old presented with melena for 3 weeks duration. Endoscopy identified a large ulcerated tumor (3 cm × 4 cm × 4 cm) in ileum proximal to Bauhin’s valve. Punch biopsies showed broad coagulative necrosis without apparently viable cells, but cell contours were recognizable. Diagnosis was impossible on HE-section, but it suggested malignancy. Since the patient denied second endoscopy, the author managed to make the diagnosis of necrotic punches. Immunohistocheimcally, the coagulative necrosis cells were positive for vimentin, CD45, CD3, CD4, CD5, CD10, CD15, CD30, CD43, CD45RO, p53, and Ki-67 (labeling = 78%). They were negative for cytokeratin (CK) AE 1/3, CK CAM5.2, CK5, CK6, CK7, CK8, CK18, CK19, CK20, EMA, p63, CD8, CD20, CD38, CD138, CD23, CD79α, κ-chain, λ-chain, bcl-2, bcl-6, cyclinD1, CD56, CD57, TdT, chromogranin, synaptophysin, NSE, S100 protein, smooth muscle actin, MUC1, MUC2, MUC5AC, MUC6, KIT and PDGFRA. Since CD30 and CD15 were strongly positive, Hodgkin’s disease and ALCL were considered. However, Hodgkin’s disease was unlikely because no apparent Hodgkin’s or Reed-Sternberg cells were seen. Therefore, CD30-positive ALCL was diagnosed. In addition, because the tumor cells expressed only T-cell markers, the diagnosis of CD30-positive T-cell ALCL was confirmed. The present study could not detect ALK, ALK/NPN, ALK-1, p80, and tissue destructive molecules such as perforins, TIA-1, and granzyme B because tumor cells were totally necrotic. Chromosomal translocation of t (2; 5) and TCR rearrangement could not be performed due to no viable cells. Post-diagnosis whole body examinations using CT, MRI, and PET showed bladder metastasis and multiple lymph node swellings in the para-aortic areas (Ann Arber Stage 4). The patient is now treated by chemotherapy and radiation for 5 months. The present study showed a very rare case of ileal CD30-positive T-cell ALCL and indicated that lymphoma diagnosis is possible even in coagulatively necrotic tissues.

Severe cytomegalovirus colitis with highly elevated sIL-2R mimicking aggressive transformation of adult T-cell lymphoma.

A smouldering adult T-cell leukaemia/lymphoma (ATLL) patient was admitted because of multiple erosions in the colon, which were infiltrated by a mixed population of lymphocytes. PET/CT demonstrated diffuse 18F-Fluorodeoxyglucose accumulation in the whole colon accompanied by multiple lymph node swelling. Histological examinations of lymph node suggested aggressive transformation to lymphoma type of ATLL. However, the general condition worsened with extremely elevated LDH, cytomegalovirus pp65 and sIL-2R after the administration of prednisolone. By contrast, subsequent administration of ganciclovir with tapered prednisolone ameliorated the laboratory findings. Differential diagnosis for aggressive ATLL and serious cytomegalovirus infection is needed.

長期胆管ドレナージにより総胆管結石を来した閉塞性黄疸の1例

A 32-year-old woman complaining of epigastralgia and nausea was referred to us for a pancreatic head tumor and multiple swelling of lymph nodes. We performed endoscopic biliary drainage and biopsies from multiple whitish granular lesions in the duodenum. The result showed follicular lymphoma. The patient was treated with R-CHOP chemotherapy. After chemotherapy, we observed the reduction of multiple lymph node swellings and the pancreatic head tumor. The plastic biliary stent did not obstruct during the 16 month period. The stricture of the bile duct also improved. At the time the plastic stent was removed, we found popsicle-like common bile duct stones, which formed due to the long period biliary stenting. We performed endoscopic choledocholithotomy and the patient made steady progress. This report describes the complication of long term plastic biliary stent placement.

A case of squamous cell carcinoma initially diagnosed as cN4 with diffuse lymph node swelling which disappeared after the eradication of Helicobacter pylori

A male patient in his early seventies complained of swallowing difficulty and back pain. Esophagogastroscopy was performed and the patient was diagnosed as squamous cell carcinoma in the middle and lower part of the esophagus with a longitudinal submucosal elevation of 15 cm and S2 stage of gastric ulcer infected by Helicobacter pylori. Multiple lymph node swelling was detected not only in the mediastinum but also in the neck and the para-aortic area by CT scanning. The clinical stage was T3 N4 M0 Stage IVa. Systemic chemotherapy was applied first and the curative effectiveness was SD based on the RECIST criteria. PET revealed accumulation of FDG in the esophageal and stomach wall. These lesions were suspected to be HP-infected esophageal cancer, and Helicobacter pylori elimination was performed. After HP eradication, the tumor of the esophagus, submucosal elevation of esophagus, and gastric ulcer was markedly shrunk. Multiple lymph node swelling was definitely shrunk based on CT. Overall the early esophageal cancer remained. Endoscopic submucosal dissection (ESD) was performed. The pathological diagnosis was Type 0-IIc, pT1b(SM2), ly1, v2, pHM0, pVM0. After ESD, he indicated febrile neutropenia, was diagnosed as myelodysplastic syndrome (MDS) during the follow-up period and chose best supportive care (BSC).

P1-32-1 - Non-Hodgkin'S Lymphoma of the Peripheral T Cell Type Complicating Scleroderma

Object: Cases of concomitant collagen disease and malignant tumor have been reported, but the complication of systemic sclerosis (SSc) by malignant tumor has still small number. We encountered a patient who developed non-Hodgkin's lymphoma peripheral T cell type after the diagnosis of localized scleroderma.Case description: The patient was a 38-year-old woman who had been diagnosed with localized scleroderma. During physical examination at admission, clubbed and sausage-like fingers and Reynaud's symptoms were noted. Abdominal CT revealed marked hepatomegaly and splenoma and swelling of multiple peritoneal lymph nodes. For which cervical lymph node biopsy was performed, and revealed peripheral T cell lymphoma. Eight cycles of CHOP therapy were planned and initiated. The cough disappeared rapidly after the completion of CHOP therapy, and the skin pruritus was alleviated. Currently, the patient finished treatment at the outpatient clinic.Discussion: The association between SSc and malignant tumors remains unclear. According to the studies reported by Abu-Shakra et al. and Rosenthal, the complication of SSc by visceral malignant tumor does not occur incidentally. Increased incidences of lung cancer, breast cancer, and lymphatic proliferative disease have been reported in SSc patients. While there is no specific tendency for the site of development of malignant tumors complicating dermatomyositis and multiple myositis, the rate of complication by ML are reportedly rare. Regarding the mechanism of complication of SSc by ML, the involvement of both B cell clonal development and T lymphocyte activation-based abnormal cellular immunity have been suggested. The development of SSc as a paraneoplastic syndrome has also been considered. This patient developed lymphoma 22 months after the diagnosis of SSc, which is considered relatively early.

Recurrence of Lung Adenocarcinoma After an Interval of 15 Years Revealed by Demonstration of the Same Type of EML4–ALK Fusion Gene

We carried out an experiment on a 58-year-old man with multiple left lung tumors and swelling of multiple lymph nodes. For clinical staging and therapeutic purposes, bronchoalveolar lavage (BAL) cytology and lung biopsy were performed. The biopsy specimen revealed the left lower lung mass to be immunohistochemically ALK (anaplastic lymphoma kinase)-positive adenocarcinoma. Using the BAL specimen from the left lower lung, EML4 (echinoderm microtubule-associated protein-like 4)-ALK variant 1 fusion gene was detected by reverse transcription-polymerase chain reaction (RT-PCR). His past history showed that he had undergone an operation for lung adenocarcinoma of the right lower lobe 15 years before, and the pathological specimen at that time revealed that the lung adenocarcinoma with pleural invasion and single metastasis of mediastinal lymph node showed a mucinous cribriform pattern and/or signet-ring cell pattern. The typical histology led us to examine the ALK rearrangement in the primary lung cancer and mediastinal metastatic tumor. Immunohistochemistry (IHC) for ALK was positive, and ALK break apart fluorescence in situ hybridization (FISH) showed a positive result. Moreover, RT-PCR using formalin-fixed, paraffin-embedded tissue from the right lung cancer also demonstrated EML4–ALK variant 1 fusion gene. Although there is a possibility that the left lung cancer is de novo one with multiple metastases, detection of the same fusion gene of the very rare EML4–ALK variant 1 in both tumors suggests that the left cancer is a recurrence of the right lung cancer after an interval of 15 years.

A case of compressive optic neuropathy putatively caused by IgG4-related idiopathic orbital inflammation.

We report the case of a 58-year-old male presenting with an impairment of the left-sided visual acuity caused by compressive optic neuropathy, and marked bilateral proptosis. Blood test showed markedly elevated IgG4 (1830 mg/dl) and positive TSH receptor-stimulating antibodies (200%), but the thyroid function test were normal. Orbital MRI revealed abnormal soft tissue proliferation around the optic nerve and fusiform enlargement of the extraocular muscles. Systemic CT analysis detected multiple lymph node swelling, pseudotumor in the lung, retroperitoneal fibrosis, and kidney lesions. We considered that the eye manifestation was most likely caused by IgG4-related idiopathic orbital inflammation. Systemic administration of a moderate dose of prednisolone dramatically improved the compression of the optic nerve, as shown by the improvement of the visual acuity and the MRI findings. The clinical course made thyroid-associated ophthalmopathy unlikely. In conclusion, an overall consideration of the clinical picture and extensive work-up of any possible differential diagnosis including measurement of the serum levels of IgG4 was highly useful in making the diagnosis of the patient. ACTA MEDICA NAGASAKIENSIA 57: 29－32, 2012

A Case of Secondary Oral Syphilis Presenting with Milk Patches in the Buccal Mucosa

We report a case of secondary oral syphilis presenting with milk patches in the buccal mucosa. A 43-year-old man presented in our hospital because of gingival pain from brushing his teeth. In the bilateral buccal mucosa he had milk patches surrounded by painless erythema with a clear borderline. Multiple submandibular lymph node swellings were palpable, but general eruptions were absent. On serological examination, the RPR test result was x64 and the TPHA result was > 40,960, so a diagnosis of secondary oral syphilis was made. Oral lesions disappeared after the administration of AMPC 750 mg/day for three weeks.

P3–050 - A Case of Gastric Neuroendocrine Carcinoma with Cavernous Sinus Metastasis

Gastric neuroendocrine carcinoma (NEC) is a rare disease; the clinicopathological features are unclear, and there is no consensus on the optimal treatment strategy. A case of gastric NEC with cavernous sinus metastasis is reported. A 64-year-old woman with rheumatoid arthritis was treated with immunomodulator drugs and a biologic drug in our hospital. Computed tomography (CT) showed thickening of the gastric wall and swelling of multiple lymph nodes. Esophagogastroduodenoscopy revealed a gastric polypoid tumor, and histopathological examination of a biopsy specimen suggested NEC. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT suggested gastric malignancy and multiple bone and lymph node metastases. Chemotherapy was planned, but both of her lower legs became paralyzed. Spinal magnetic resonance imaging (MRI) showed vertebral metastases to the thoracic spinal cord. Posterior vertebral decompression was performed. One month after the operation, carboplatin plus etoposide (CE) was started according to the regimen for extensive small cell lung cancer in poor-risk patients. During the 2 cycles of CE she complained of double vision and ptosis. Brain MRI showed a metastatic tumor of the cavernous sinus. Double vision and ptosis improved with local radiation therapy (45 Gy) and CE. However, she died of disease progression 5 months after diagnosis. This case suggests that gastric NEC is an aggressive and rapidly progressive tumor that is resistant to chemotherapy, and that it may be necessary to watch for multiple organ metastases.

術前に頸部リンパ節結核の合併が判明した甲状腺癌頸部リンパ節転移の1例

We report a case of papillary carcinoma of the thyroid gland and cervical lymph node metastases with concurrent tuberculous lymphadenitis that was diagnosed preoperatively. A 35-year-old woman presented with multiple lymph node swellings and an anterior neck mass. No findings suggesting the coexistence of pulmonary tuberculosis were present. The patient underwent a total thyroidectomy with bilateral neck dissection together with medication. Measures to prevent tuberculosis were undertaken during the perioperative period. The histopathological diagnosis was papillary carcinoma with both metastatic and tuberculous lymphadenitis of the lymph nodes in the neck. The possible coexistence of tuberculous lymphadenitis must be ruled out when lymph node swellings are observed in patients with head and neck cancer, including thyroid carcinoma.

Autoimmune hemolytic anemia with warm-reactive immunoglobulin M antibody in multicentric Castleman disease

Dear Editor, Multicentric Castleman disease (MCD) is accompanied by systemic manifestations [1]. Autoimmune hemolytic anemia (AIHA) resulting from warm-reactive immunoglobulin M (wIgM) autoantibodies is rare and associated with a poor prognosis [2–4]. We report here the first case of MCD in which the clinical course was complicated by AIHA with wIgM and IgG antibodies. A 50-year-old male was admitted to our hospital because of weakness, swelling of multiple lymph nodes, and splenomegaly. Lymph node biopsy demonstrated MCD. He was treated with prednisolone (PSL) (0.5 mg/kg/day) and continued to receive maintenance therapy with PSL (10 mg/day). Three years later, he developed fever and fatigue. Upon hospital admission, he had icterus and severe anemia, but MCD activity was absent. Laboratory findings were: Hb, 3.3 g/dL; WBCs, 9,420/μL; platelets, 298,000/μL; reticulocytes, 11.3 %; total bilirubin, 2.4 mg/dL; D-dimer, 3.46 ng/mL; and CRP, 0.95 mg/dL. Anti-autoantibodies (including antiphospholipid antibody) were all negative, as were blood cultures. RBC histograms indicating the mean corpuscular volume (MCV), by a Blood Cell Counter, revealed several large peaks, suggesting hemagglutination in vivo (Fig. 1a). RBCs showed spontaneous agglutination at 37 °C in vitro and, after washing with physiological saline at 43 °C, hemagglutination was finally resolved. We could not carry out a direct antiglobulin test (DAT) due to undissolved material. After treatment of RBCs with 2mercaptoethanol (2-ME), the DAT for IgG and C3d remained positive. Eluted autoantibodies revealed direct hemagglutination. Finally, we confirmed a large amount of IgM and a small amount of IgG on the surface of RBCs by flow cytometry (FCM) (Fig. 1b). Thus, the patient was diagnosed with AIHA due to a high titer of wIgM and a low titer of IgG. Although he received combination treatment of PSL (1 mg/kg/day) and intravenous Ig, he had ongoing hemolysis, hemagglutination, and severe anemia (Hb, 2.2–4.7 g/dL) and required multiple blood transfusions. Ten days after hospital admission, he developed fluctuant disturbances in consciousness, and multiple cerebral thromboembolism (TE) as diagnosed by magnetic resonance imaging (MRI) of the brain (Fig. 1c). We immediately administered chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab (CHOP-R)) with continuous intravenous infusion of low-molecular-weight heparin. Hb levels gradually increased to 9.9 g/dL, and the large peaks of MCV in the RBC histogram disappeared (Fig. 1a). On follow-up, symptoms including neurological deficits had resolved, and MRI showed recovery from TE. DAT remained weakly positive for IgG and C3d. Sometimes, wIgM antibodies cannot be detected by the DAT. This may be because DAT cannot be carried out due to strong resistant hemagglutination; also, the routine DAT does not contain anti-IgM antibody [5]. The indirect AT is frequently negative or weak because most of the wIgM antibodies are absorbed by RBCs [5]. In our patient, the DAT could not be carried out but the indirect AT revealed K. Tajima (*) Department of Radiation Emergency Medicine, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba-shi, Chiba 263-8555, Japan e-mail: tajima@nirs.go.jp