Non-Hodgkin's Lymphoma with Pelvic Skeletal Muscle Involvement Presenting as Low Back Ache: An Uncommon Presentation of a Rather Common Malignancy.

Lymphoma with skeletal muscle involvement is a rare clinical presentation. They may occur as primary skeletal muscle lymphoma, contiguous spread from bones or by metastatic spread. We present a rare case of non-Hodgkin's lymphoma with pelvic skeletal muscle involvement presenting as low back ache. Lymphoma as the first differential diagnosis in this case was clinched after an 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and confirmed as diffuse large B-cell lymphoma on histopathology. We seek to present an uncommon manifestation of lymphoma and highlight the role of 18F-FDG PET CT in the diagnosis, staging, and management of lymphoma.

Introduction

Non-Hodgkin's lymphoma (NHL) is a common hematological malignancy with the highest incidence of NHL being reported from countries with a very high human development index.[1] The burden of NHL in 2012 for India was estimated to have an incidence rate of 2.2/100,000 (23,801 new cases) and a mortality rate of 1.5/100,000 (16,597 deaths).[1] Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of NHL, accounting for more than one-third of all lymphomas.[2] Although DLBCL generally involves the lymph nodes, it can arise in other tissues such as intestine, bone, breast, liver, skin, lung, and the central nervous system. Because normal healthy skeletal muscle does not contain lymphoid tissue, extranodal lymphoma involving skeletal muscles are quite rare. We present a rare case of NHL-DLBCL with skeletal muscle involvement detected by an 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG PET-CT) and confirmed by histopathology.

Case Report

A 47-year-old male patient with no known comorbidities presented with a history of the low backache of 2 months. The pain was insidious in onset, involving the lower back predominantly on the right side, dull aching in character, gradually progressive, nonradiating, aggravated by movement, and relieved by rest and analgesics. The patient had no history of early morning stiffness, numbness or tingling sensation in the lower limbs or pain and swelling in any of the joints. There was no history of any trauma or any physical strain before onset of pain. There was no associated history of bowel or bladder incontinence, recent fever or unexplained weight loss. No history of any congenital abnormalities in the spine or family history of low back ache. Clinical examination revealed nontender, subcentimetric, bilateral supraclavicular lymph nodes. Local examination revealed tenderness over the lumbosacral spine and right sacroiliac joint. Schober's test revealed the extent of lumbar flexion to be more than 5 cm. Systemic examination was unremarkable. Laboratory investigations revealed a normal hemogram and liver function tests along with elevated erythrocyte sedimentation rate of 42 mm/h and serum creatinine of 1.4 mg/dl. Magnetic resonance imaging (MRI) scan of lumbosacral spine revealed altered signal intensity which was hyperintense of T2-weighted/short-tau inversion recovery (STIR) images and hypointense on T1-weighted images in bilateral iliac blades, bilateral acetabuli and soft tissue adjacent to outer cortex of right iliac blade. There was also evidence of multiple focal areas of altered signal intensity which was hyperintense on T2-weighted/STIR and hypointense on T1-weighted images in the lumbosacral vertebrae. Based on the above findings and mildly increased serum creatinine, there was a clinical suspicion of multiple myeloma. Patient was worked up for urine Bence–Jones proteins and serum electrophoresis which was normal. Bone marrow aspiration study revealed no evidence of any plasma cell dyscrasia. Tumor markers including alpha-fetoprotein, CA125, CA19-9, beta-human chorionic gonadotropin and prostate-specific antigen were within normal limits. However, the serum lactate dehydrogenase levels were elevated (570 IU/L). The patient was then subjected to a whole body 18F-FDG PET-CT [Figures 1 and 2]. The scan revealed an FDG avid soft tissue density lesion in the abdomen along the midline extending from the level of LV-1 to LV-3, likely a conglomerate lymph nodal mass. An ill-defined isodense round to oval hypermetabolic lesion predominantly involving the right gluteus medius and right iliacus muscles was noted adjacent to right ilium near sacroiliac joint with a small area of cortical erosion on the lateral aspect of right ilium. Mildly FDG avid lymphadenopathy involving right cervical, right supraclavicular, right axillary, and left inguinal lymph nodes were noted. FDG avid lesions involving multiple lumbosacral vertebrae, right ilium, left ilium near sacroiliac joint, the roof of the right acetabulum and head of left femur with no obvious CT abnormality were also noted. PET-CT findings lead to fresh clinical suspicion of a lymphoproliferative disorder along with a differential diagnosis of sarcoma. The patient was further subjected to an ultrasound guided tru-cut biopsy of the lesion in right gluteus medius and a bone marrow biopsy. The tru-cut biopsy of the gluteal lesion revealed intermediate to large-sized atypical lymphoid cells infiltrating the muscle fibers in the form of sheets and singly scattered patterns, having round to oval hyperchromatic nuclei and moderate nuclear pleomorphism [Figure 3]. Further immunohistochemistry (IHC) panel revealed CD20, CD79a, MUM1, Bcl6, and Bcl2 to be positive, along with scattered positivity of CD3 and a Ki67 index of 80%–90% [Figure 4]. Based on the microscopic findings and IHC panel, a diagnosis of high-grade NHL DLBCL was made. Bone marrow biopsy revealed the involvement of bone marrow by high-grade B-cell NHL. Based on imaging and histopathology findings a diagnosis of high-grade B-cell NHL stage IV was made with risk stratification on International Prognostic Index of 3 (low-intermediate risk). The patient was, therefore, started on chemotherapy on rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone protocol. The patient was subjected to an interim PET for response evaluation after three cycles of chemotherapy. Interim PET-CT scan revealed no abnormal FDG avid lesion in the scanned region of the body and the patient was classified as having a complete metabolic response (CMR) under interim PET evaluation criteria of Lugano classification [Figure 5]. Based on the PET-CT findings, the oncologist decided to complete the planned treatment protocol.

Figure 1

Maximum intensity projection image of fluorodeoxyglucose positron emission tomography computed tomography showing involvement of right gluteal muscles (red arrow), ill-defined mass in the abdomen - likely conglomerate lymph nodal mass (green arrow) and bone marrow deposits (orange arrow)

Figure 2

(a) Axial fused positron emission tomography computed tomography image showing fluorodeoxyglucose avid involvement of right gluteus medius and right iliacus muscles. (b) Axial fused positron emission tomography computed tomography image showing marrow involvement in right iliac bone. (c) Sagittal fused positron emission tomography computed tomography image showing fluorodeoxyglucose avid ill-defined mass in the abdomen - likely conglomerate lymph nodal mass and bone marrow deposits

Figure 3

(a) H and E stained sections of trucut biopsy from right gluteus medius muscle in low (40×) magnification showing intermediate to large sized lymphoid cells infiltrating the muscle fibers to form sheets and singly scattered patterns. (b and c) H and E stained sections of the same biopsy in higher magnification (100× and 200 ×). (d) H and E stained sections of the same biopsy in 400× magnification showing lymphoid cells having round to oval hyperchromatic nuclei with moderate nuclear pleomorphism

Figure 4

Immunohistochemisty panel revealing (a) BCl6 positivity (b) CD3 positivity (c) CD20 positivity (d) CD79a positivity (e) MUM1 positivity and (f) Ki-67 index of 80%−90%

Figure 5

Maximum intensity projection image of interim fluorodeoxyglucose positron emission tomography computed tomography showing complete metabolic response to therapy

Discussion

Lymphoma comprises a histologically heterogeneous group of neoplasms derived from the lymphoid cells of the immune system, the hallmark of which is the enlargement and proliferation of lymph nodes or secondary lymphoid tissues. The term extranodal is used in cases where there is neoplastic proliferation at sites other than the expected native lymph nodes or lymphoid tissues. A retrospective review of 3556 cases of NHL by Gurney and Cartwright revealed that nearly one-third of all NHL cases were extranodal in origin, giving an incidence of 1.9/105 new cases per year.[3] The most common extranodal sites of involvement were stomach, central nervous system, lungs, bones, and skin.[34] Lymphomatous involvement of muscles has been reported to occur in only 1.4% of cases, with 0.3% occurring in Hodgkin lymphoma and 1.1% in NHL.[5] The most common route of muscle involvement is metastatic spread from adjacent lymph nodes or other primary sources such as bone.[67] Lymphoma spreads by infiltration of malignant cells that lack extracellular stroma and intercellular junctions, resulting in diffuse enlargement of involved structures passing fascial boundaries. Thus, the involvement of more than one muscle compartment is typical. CT and MRI images may show diffuse enlargement of the involved organs. Attenuation on CT is similar or slightly decreased compared with uninvolved muscles; enhancement after IV contrast injection may be unapparent.[78] Our patient presented with low back ache with an initial clinical suspicion of multiple myeloma based on initial imaging and laboratory investigations. However, the subsequent directed investigations including bone marrow aspiration ruled out any plasma cell dyscrasia. The 18F-FDG PET-CT findings and metabolic-guided biopsy helped in clinching the diagnosis of NHL-DLBCL. Patient responded well to chemotherapy and was classified as having CMR under interim PET evaluation criteria of Lugano classification.[9] This case is a rare presentation of extranodal lymphoma with involvement of skeletal muscles.

Conclusion

This case report presents a rare case of NHL-DLBCL with skeletal muscle involvement. Lymphomatous involvement of muscle, although rare must be suspected in cases where there are conventional imaging findings of bone/marrow lesions with contiguous skeletal muscle involvement and in cases of nonresolving swelling of the extremities. This case further highlights the burgeoning role of 18F-FDG PET-CT in the diagnosis and staging of NHL. However, a biopsy is necessary for a final and conclusive diagnosis, which may be followed by IHC if the cell type of the tumor is uncertain.

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Conflicts of interest

There are no conflicts of interest.