Article, Oncology

Rhabdomyolysis caused by peripheral T-cell lymphoma in skeletal muscle

Unlabelled image American Journal of Emergency Medicine 31 (2013) 1537.e3-1537.e5

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Case Report

Rhabdomyolysis caused by peripheral T-cell lymphoma in skeletal muscle?

Abstract

We report a rare case of rhabdomyolysis caused by peripheral T- cell lymphoma (PTCL) in skeletal muscle. A 62-year-old man was admitted with complaints of sudden muscle weakness. Laboratory abnormalities were identified including markedly elevated creati- nine-phosphokinase, peaking at 62,640 IU/L and serum creatinine (Cr) at 5.0 mg/dL. computed tomography scans revealed tumorous swelling of the right psoas major muscle and the obturator internus muscles. Consequently, he was diagnosed with acute renal failure caused by rhabdomyolysis and was treated with hydration and continuous hemodiafiltration, which resulted in significant improve- ment in renal function (Cr 1.79 mg/dL). However, the cause of the rhabdomyolysis remained unclear, and he suddenly developed a remittent fever and suffered from Hemophagocytic Syndrome. Serum ferritin level dramatically increased to 104,707.0 ng/mL and creati- nine level to 4.09 mg/dL. We performed a biopsy of inguinal lymph nodes, leading to a diagnosis of PTCL. Finally, he was diagnosed with rhabdomyolysis caused by PTCL. Methylprednisolone pulse therapy markedly improved his general condition and renal function (Cr 1.48 mg/dL), and computed tomography scans revealed that tumorous swelling was greatly diminished. Except when the cause of rhabdo- myolysis is readily apparent, such as in cases of trauma, drug and thrombophlebitis, one should consider that rhabdomyolysis may be a sequel of lymphoma.

Lymphoma involving skeletal muscle is relatively rare, compris- ing only 1.5% of cases of non-Hodgkin’s lymphoma and 0.3% of Hodgkin’s lymphoma [1]. Lymphoma in skeletal muscle often invades multiple compartments and can lead to compartment syndrome resulting in rhabdomyolysis [2]. Here, we report a rare case of rhabdomyolysis caused by peripheral T-cell lymphoma in skeletal muscle.

A 62-year-old man with a history of diabetes, hypertension, and cerebral infarction was admitted to another hospital complaining of general fatigue and sudden muscle weakness. Examination revealed fever and acute renal failure (ARF) with anuria that continued despite hydration. He was emergently transferred to our medical center for further evaluation and treatment. On arrival, physical examination confirmed the presence of swelling and tenderness in the right hip and left femoral region. Laboratory abnormalities were identified, including markedly elevated creatinine-phosphokinase levels (peak- ing at 62,640 IU/L) and a serum creatinine (Cr) level of 5.0 mg/dL. Computed tomography (CT) revealed tumorous swelling of the right Gluteus maximus and medius (Fig. 1A), and magnetic resonance imaging confirmed hematomas in those muscles.

? Disclosures: The authors declare no conflicts of interest.

Given the above findings, ARF caused by rhabdomyolysis was diagnosed and treatment with hydration and continuous hemodia- filtration started, resulting in significant improvements in physical strength and renal function (Cr, 1.79 mg/dL). However, the cause of the rhabdomyolysis remained unclear. Further, although the rhabdomyolysis improved, the patient suddenly developed a persistent fever of 38?C. While the primary cause of the remittent fever was unknown, infection was initially suspected and the patient was started on a course of antibiotics, but the fever did not improve.

In addition, the serum ferritin level increased dramatically from

441.5 to 104,707.0 ng/mL, and the Cr level again increased to 4.09 mg/dL. Frequent blood transfusions were required to treat pancyto- penia, and the patient rapidly developed enlarged lymph nodes throughout his body. Hemophagocytic syndrome (HPS) was sus- pected because of the abnormally high serum ferritin levels; in fact, the patient fulfilled the standard criteria for the diagnosis of HPS, such as recurrent fever, cytopenia involving two or more cell lines, splenomegaly, hepatitis, and hypertriglyceridemia [3]. While, biop- sies of the bone marrow and inguinal lymph nodes performed to identify the cause of the HPS. Bone marrow biopsy did not show any lymphoma involvement. However, the pathology indicated that tumors had infiltrated the lymph nodes, with vaguely nodular proliferation of atypical lymphocytes ranging in size from small to large cells (Fig. 2).

Immunohistochemical staining revealed that the atypical lym- phocyte populations were positive for CD2, CD3, CD4, CD8, TCR?, TIA- 1, and granzyme B, and negative for CD5, CD10, CD30, CD20, CD45RO, CD56, CD79a, bcl-6, ALK, and EBER-ISH. Serology was negative for anti-HTLV antibodies. The histology was consistent with periph- eral T-cell lymphoma (PTCL), which was considered to be the cause of the HPS. Methylprednisolone pulse therapy for HPS and PTCL resulted in marked improvement of his general condition, pancyto- penia, and renal function (Cr, 1.48 mg/dL). The above findings suggest that HPS caused the renal function deterioration. Further, CT showed clear reductions in the tumorous swelling of the right gluteus maximus and medius (Fig. 1B). Taken together, these results suggested that PTCL caused the rhabdomyolysis. Because the HPS and PTCL improved, he was transferred to a facility with hematology specialists for additional chemotherapy.

Only three previous reports of malignant lymphoma in skeletal muscle with rhabdomyolysis have been documented [4-6] (Table). In concordance with the previous reports, T-cell lymphoma occurred in the lower limbs in the present case and involved the gastrocnemius, psoas, gluteal, and soleus muscles. Malignant lymphoma in skeletal muscles is known to occur in B-cell lymphoma; however, all reported cases were T-cell lymphomas. These findings suggest that the lymphoma developed into rhabdomyolysis because a cytotoxic factor caused the lymphoma to develop and invade aggressively.

1537.e4 K. Sasaki et al. / American Journal of Emergency Medicine 31 (2013) 1537.e3-1537.e5

Fig. 1. Pelvic CT. The gluteus maximus and medius are indicated by black asterisks. CT scans reveal that the tumorous swellings of the gluteus maximus and medius have greatly diminished. (A) On admission to the emergency unit. (B) After administration of methylprednisolone.

Fig. 2. Histology of the left inguinal node biopsy specimen. The medium- or large-sized lymphoidocytes show nuclear polymorphism and diffuse hyperplasia. Hematoxylin and eosin stainings: (A) 200 x magnification, (B) 1000x magnification.

B-cell lymphoma with mild invasion could not cause rhabdomy- olysis leading to ARF following muscle infiltration. The effusion on CT at the time of emergency unit hospitalization was blood that had leaked from disrupted blood vessels. These results show that the effusion diminished because of absorption of blood into the gluteal muscles. Damage to muscle tissue from lymphoma can be caused by three mechanisms: invasion of muscle from a neighboring lymph- adenopathy, invasion of metastases, or primary skeletal muscle lymphoma [7]. Because the right gluteus maximus and medius contributed to the pathogenesis of PTCL, muscle biopsy would be necessary for a definite diagnosis.

However, we were unable to perform a muscle biopsy for several reasons. First, given that biopsy results will typically be uninformative

at an early stage, it is important to wait several weeks or months after the clinical event of rhabdomyolysis to perform a biopsy [8], because the results of a biopsy will typically be uninformative at an early stage. Second, Diez et al reported that muscle biopsy was non- diagnostic [4]. Given that lymphoma is a systemic illness, there was no need to search for a primary focus when the lymphoma spread throughout the body.

The probability of making the diagnosis was low, even if a muscle biopsy were performed; therefore, a muscle biopsy was not performed. In addition, except in the present case, all previous patients died. In the previously documented cases, T-cell lymphoma resulted in the aggressive proliferation of cytotoxic factors as rhabdomyolysis developed. Even if discovery and treatment are

Table

Clinical information in 4 patients with malignant lymphoma in skeletal muscle with rhabdomyolysis

	Age	Sex	Type	Location	Pathologic findings	Outcome
Diez-Martin et al (1990)	24	Male	Nonprimary	Gastrocnemius	Peripheral T cell lymphoma	Death
Vural et al (2002)	48	Male	Nonprimary	psoas muscle	Nasal-type	Death
Masaoka et al (2002)	56	Male	Primary	Gluteal muscle Gatrocnemius	T/natural killer-cell lymphoma Non-Hodgkin’s lymphoma diffuse T cell origin	Death
Our case (2012)	62	Male	Nonprimary	Soleus muscle Psoas muscle	Peripheral T cell lymphoma
				Gluteal muscle		Alive

K. Sasaki et al. / American Journal of Emergency Medicine 31 (2013) 1537.e3-1537.e5

possible, a fatal outcome can be expected. Fortunately, the lymphoma was detected promptly in the present case, the T-cell lymphoma achieved remission with chemotherapy after transfer to

1537.e5

Keiko Yasuda MD Hiromi Rakugi MD Yoshitaka Isaka MD

another hospital, and the patient remained alive six months after the diagnosis.

The association of HPS with PTCL is a well recognized entity that can be mediated by cellular components [9]. Severe HPS has been reported to lead to ARF in 30% to 50% of cases [10,11], and ARF was associated with Nephrotic syndrome in many cases. Renal histology in previous cases of HPS showed acute tubular necrosis associated with collapsing glomerulopathy, minimal change glomerulopathy, and thrombotic-microangiopathy with abnormal podocytes [12]. Howev- er, a renal biopsy could not be performed in the present case because of the patient’s extremely poor general condition. Proteinuria increased dramatically from 260 to 1358 mg/day with exacerbation of HPS. Nonetheless, the proteinuria decreased to 228 mg/day with the improvement of HPS following the methylprednisolone pulse therapy. These results suggested that the ARF was caused by HPS in the present case. Further, the patient’s renal function improved to normal levels (Cr, 0.82 mg/dL) with additional chemotherapy after transfer to another hospital.

Except when the cause is readily apparent, such as in cases of trauma, exertion, Adverse drug reaction, infection, or elec- trolyte disorders, rhabdomyolysis should be considered a sign of lymphoma.

Koichi Sasaki MD

Department of Nephrology Osaka Kosei Nenkin Hospital, Osaka, Japan E-mail address: [email protected]

Masaya Yamato MD

Department of Nephrology Rinku General Medical Center, Osaka, Japan

Department of geriatric medicine and Nephrology Osaka University Graduate School of Medicine

Osaka 553-0003, Japan

http://dx.doi.org/10.1016/j.ajem.2013.05.034

References

AJEM

Rhabdomyolysis caused by peripheral T-cell lymphoma in skeletal muscle

Henter JI, Elinder G, Ost A. Diagnostic guidelines for hemophagocytic lymphohis- tiocytosis. The FHL Study Group of the Histiocyte Society. Semin Oncol 1991;18: 29-33.

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