Brain Pathology Case of the Month - May 2018

FINAL DIAGNOSIS

Myopathy secondary to intravascular large B-cell lymphoma (IVLBCL), non-germinal center subtype.

DISCUSSION

Intravascular diffuse large B-cell lymphoma is a rare and aggressive form of non-Hodgkin's lymphoma, defined by the World Health Organization as a distinctive extranodal lymphoma characterized by intravascular growth, with a predilection for small blood vessels (capillaries and post-capillary venules). Organs involved differs by geography: in Western countries, clinical presentation is usually with neurological and cutaneous manifestations; while Asian forms usually show pancytopenia, hepatosplenomegaly, multiorgan failure and hemophagocytic syndrome(5). To the best of our knowledge, this is the seventh patient reported with IVLBCL and associated symptomatic muscle involvement (4).

Although the underlying mechanism for this growth pattern in lymphomas is not well understood, the lack of surface integrins and adhesion molecules may restrict extravasation of lymphoma cells (6). Patients are frequently older (more than 60 years) and diagnose is often not reached until autopsy because of many unspecific radiological signs and many unrelated clinical symptoms. In addition, most of the diverse symptomatology caused by this entity is due to occlusion of the vessel and consequently tissue infarction. B symptoms (e.g. fever, weight loss, night sweats) are also a common presentation as well(7). Additionally, the association between lymphoma and myopathy is well-known as paraneoplastic manifestations but, unlike the present case, lymphomas usually induce an inflammatory myopathy or less commonly a necrotising myopathy or neuromuscular junction defects, becoming this entity a remarkable diagnostic challenge (1, 2). However, although muscle weakness, in this case, could be explained by previous steroid therapy, it has been described that IVLBCL could also induce muscle weakness due to a nuclear antigen expressed by myocytes and neoplastic cells by an unknown underlying mechanism(4). We also observed additional indirect damage of peripheral nerves due to some angular atrophic esterase-positive muscle fibers that could have contributed to muscle weakness. In conclusion, we suggest that all clinical symptoms observed from the very beginning could be explained by the underlying presence of IVLBC. However, we point out that forms of vasculitis like PAN could be related to the appearance of other conditions such as lymphoma (3). Finally, the patient underwent chemotherapy and she recovered from their weakness and symptoms for two months. However, she unfortunately passed away due to sepsis nine months after clinical onset.

REFERENCES

  1. Argov Z, Shapira Y, Averbuch-Heller L, Wirguin I (1995) Lambert-Eaton myasthenic syndrome (LEMS) in association with lymphoproliferative disorders. Muscle & nerve.18(7):715-9.
  2. Buchbinder R, Forbes A, Hall S, Dennett X, Giles G (2001) Incidence of malignant disease in biopsy-proven inflammatory myopathy. A population-based cohort study. Annals of internal medicine.134(12):1087-95.
  3. Fain O, Hamidou M, Cacoub P, Godeau B, Wechsler B, Paries J, Stirnemann J, Morin AS, Gatfosse M, Hanslik T, Belmatoug N, Bletry O, Cevallos R, Delevaux I, Fisher E, Hayem G, Kaplan G, Le Hello C, Mouthon L, Larroche C, Lemaire V, Piette AM, Piette JC, Ponge T, Puechal X, Rossert J, Sarrot-Reynauld F, Sicard D, Ziza JM, Kahn MF, Guillevin L (2007) Vasculitides associated with malignancies: analysis of sixty patients. Arthritis and rheumatism.57(8):1473-80.
  4. Marini-Bettolo C, Lane R, Charles P, Naresh K, Nicholas R, Singh P, Cohen A, Mackie P, Roncaroli F (2009) Myopathy secondary to intravascular large B-cell lymphoma. Neuromuscular disorders : NMD.19(12):856-9.
  5. Menon MP, Pittaluga S, Jaffe ES (2012) The histological and biological spectrum of diffuse large B-cell lymphoma in the World Health Organization classification. Cancer journal.18(5):411-20.
  6. Ponzoni M, Arrigoni G, Gould VE, Del Curto B, Maggioni M, Scapinello A, Paolino S, Cassisa A, Patriarca C (2000) Lack of CD 29 (beta1 integrin) and CD 54 (ICAM-1) adhesion molecules in intravascular lymphomatosis. Human pathology.31(2):220-6.
  7. Rajyaguru DJ, Bhaskar C, Borgert AJ, Smith A, Parsons B (2017) Intravascular large B-cell lymphoma in the United States (US): a population-based study using Surveillance, Epidemiology, and End Results program and National Cancer Database. Leukemia & lymphoma.1-9.

Contributed by Bernardo-Cofiño J, MD, Gómez-Illán R, MD, Nicolás C, MD, Astudillo A, MD, PhD and Fernandez-Vega I, MD PhD

International Society of Neuropathology