The scale of the problem that motivated the study is considerable. According to the 2022 GLOBOCAN report, non-Hodgkin lymphoma ranks as the tenth most common cancer worldwide and the eleventh leading cause of cancer death, striking males more often than females. But the geographic distribution of the pediatric burden is strikingly skewed: roughly 84 percent of cases in children under 16 occur in Latin America, Africa, Asia, the Caribbean, and Polynesia, and an estimated 80 percent of children who develop these tumors live in developing countries. In Ghana specifically, non-Hodgkin lymphoma is the third leading cause of childhood cancer death and accounts for about 7 percent of childhood neoplasms. A three-year review at Korle Bu Teaching Hospital found that lymphomas made up over 60 percent of childhood malignancies, with Burkitt lymphoma the most common type.

Diagnosing and classifying these tumors accurately is far harder than it might seem. The World Health Organization recognizes more than 50 subtypes of non-Hodgkin lymphoma, distinguished by clinical presentation, tumor cell morphology, antigenic marker expression, and genetic features. Morphology alone—the appearance of cells under a microscope after standard hematoxylin and eosin staining—is often insufficient, because many subtypes closely resemble one another. The WHO explicitly warns that morphological assessment by itself risks discordant reports even among experienced pathologists, complicating the identification of rare and heterogeneous cases and hindering the planning of targeted therapy. In well-resourced health systems, immunophenotypic testing, cytogenetics, and molecular assays are routinely folded into the diagnostic workup, and there is solid evidence that this integration improves clinical outcomes and overall survival. In Ghana and much of Africa, however, treatment typically proceeds on the basis of clinical and histological information alone, because laboratories lack equipment, reagents are costly, and trained personnel are scarce.

The consequence, the researchers note, is that many children may be treated without a definitive pathological diagnosis—either undertreated, or given unnecessarily high doses of chemotherapy that are toxic and harmful. Against this backdrop, the team set out to evaluate the immunophenotypic characteristics of three non-Hodgkin lymphoma subtypes and the survival outcomes of the children bearing them, using three markers with distinct biological roles: CD3, which broadly marks T lymphocytes and helps establish tumor cell lineage; CD25, the interleukin-2 receptor alpha chain, which reflects host immune response within the tumor microenvironment; and BCL-2, a protein that blocks programmed cell death and is associated with resistance to apoptosis and chemotherapy.

The methodology was meticulous given the constraints. The team retrieved formalin-fixed, paraffin-embedded tissue blocks from the hospital’s pathology archives, identifying 133 cases of children under 18 who were clinically diagnosed with non-Hodgkin lymphoma between 2018 and 2022. Children with incomplete data, inadequate tissue, or HIV co-infection were excluded. Thin sections cut from each block were stained with hematoxylin and eosin, and two independent pathologists at the Kwame Nkrumah University of Science and Technology reviewed every slide while blinded to previous reports; any disagreement was adjudicated by a third pathologist. Of the initial 133 cases, 38 were confirmed as showing the histomorphological features of non-Hodgkin lymphoma—diffuse effacement of normal nodal architecture, atypical lymphoid proliferation, increased mitotic activity, and loss of normal germinal center structures—and were suitable for immunohistochemistry.

For the immunohistochemical analysis, serial sections underwent heat-induced epitope retrieval in citrate buffer, blocking of endogenous peroxidase and non-specific protein binding, and staining with mouse monoclonal antibodies against CD3, CD25, and BCL-2. Signal was detected with an enzyme-conjugated secondary antibody and a chromogenic substrate, producing brown staining visible under a light microscope. Known positive control tissues—tonsil for CD3 and reactive lymph node for BCL-2 and CD25—accompanied each staining batch, while negative controls omitted the primary antibody. Two pathologists independently scored both staining intensity, on a scale from zero to strong, and the proportion of tumor cells stained, from under 20 percent to over 80 percent, with a third pathologist resolving discrepancies. Combined scores ranked each case as showing no, low, moderate, or high expression.

The results revealed a distinctly heterogeneous immunophenotypic landscape. BCL-2 was the most frequently expressed marker, present in 55.3 percent of cases, followed by CD3 in 36.8 percent, while CD25 was expressed in only 5.3 percent of patients. Co-expression occurred at varying levels, with 28.9 percent of cases expressing both BCL-2 and CD3, and 5.3 percent expressing all three markers simultaneously. Stratifying expression by clinical aggressiveness added nuance: BCL-2 showed high expression in 76.9 percent of low-grade cases, moderate expression in half of high-grade cases, and low expression in 36.4 percent of Burkitt lymphomas. Notably, although Burkitt lymphoma is classically characterized by absent or low BCL-2 expression, a substantial subset of the Burkitt cases in this cohort were positive—consistent with emerging evidence from other studies, including reports of BCL-2 positivity in roughly 23 percent of Burkitt lymphoma cases in European and adult series, which challenges the diagnostic utility of this marker and underscores the biological heterogeneity of these tumors.

The survival data were sobering. Of the 38 participants, 21 had complete follow-up data for survival analysis. Median overall survival from diagnosis was 22 months, with survival rates of 76 percent at 10 months, 61 percent at 20 months, 40 percent at 30 months, and 20 percent at 40 months—a steep and steady decline. The clinical outcomes were equally stark: 30.6 percent of patients died while on admission for chemotherapy, 27.8 percent abandoned treatment, 2.8 percent died shortly after discharge, and only 38.8 percent survived and were discharged. When the researchers used log-rank tests to identify factors associated with survival, age, gender, duration of symptoms, CD3 expression, CD25 expression, and clinical aggressiveness showed no significant association. But BCL-2 expression was significantly linked to inferior survival (p = 0.030)—patients expressing the marker had a median survival of 12 months versus 30 months for those who did not—and nodal or extranodal involvement was even more strongly associated (p < 0.001). This aligns with the biology: BCL-2 proteins downregulate apoptosis and promote chemoresistance, while spread to multiple nodal and extranodal sites signals advanced, aggressive disease, a principle embedded in the staging systems used for pediatric lymphoma.

The study’s limitations temper its conclusions, and the authors are candid about them. Poor archiving systems meant many tissue blocks could not be retrieved, shrinking the sample and limiting statistical power—the cohort was underpowered for multivariable Cox proportional hazards modeling, so survival findings warrant caution. The retrospective design prevented standardization of chemotherapy and clinical care, and survivors were not followed long-term. Because no B-cell lineage markers such as CD20, MYC, CD10, BCL6, or Ki-67 were included, the lineage of CD3-negative tumors could not be definitively determined, and CD3 positivity alone cannot distinguish neoplastic T cells from background reactive infiltrates—meaning the apparent proportion of T-cell lymphomas should be interpreted cautiously, even though it was higher than previously reported in Ghana. Cases were also grouped by clinical aggressiveness rather than formal WHO classification. Yet the core message stands: in a setting where most children present with advanced disease, treatment abandonment is common, and advanced immunophenotypic stratification is unavailable, simple and affordable biomarker panels like the one tested here could offer a practical first step toward effective patient stratification and, ultimately, better survival outcomes for children with non-Hodgkin lymphoma in Ghana and similar resource-limited settings.

Subject of Research: Immunophenotypic biomarker expression and survival outcomes in childhood non-Hodgkin lymphoma in Ghana

Article Title: Assessment of Selected Immunophenotypic Markers in Childhood Non‐Hodgkin's Lymphomas in Ghana: A Possible Tool for Effective Stratification of Patients and Assessment of Survival Outcomes

Article References: Sakyi, S. A., Gyan, B., Adankwah, E., Adjei, E. K., Paintsil, V., Adu, D. K., Owusu, M. A., Dagungong, C. B., Tanko, M. M., Zogli, K. E., Effah, A., Agomuo, S. K. S., Kwarteng, S., Nyantakyiwaa, B., Gyimah, E. O., Diawuo, H. Y., Owusu, G. O., Senu, E., Mensah, O. S. O., … Fondjo, L. A. (2026). Assessment of Selected Immunophenotypic Markers in Childhood Non‐Hodgkin's Lymphomas in Ghana: A Possible Tool for Effective Stratification of Patients and Assessment of Survival Outcomes. Cancer Reports, 9(10), Article e70711. https://doi.org/10.1002/cnr2.70711

Image Credits: AI Generated

DOI: 10.1002/cnr2.70711

Keywords: non-Hodgkin lymphoma, pediatric oncology, Ghana, BCL-2, CD3, CD25, immunohistochemistry, survival analysis, Burkitt lymphoma, resource-limited settings, biomarkers, treatment abandonment

The case, published in the journal Cancer Reports, documents how progressive proximal muscle weakness and markedly elevated creatine phosphokinase (CPK) preceded any recognizable sign of lymphoma. On examination, the patient demonstrated symmetric weakness of the shoulder and hip girdle muscles, scoring 3 out of 5 on the Medical Research Council strength scale—able to move against gravity but not against resistance. Deep tendon reflexes were reduced, but cranial nerves, sensation, and sphincter function were intact, pointing clinicians toward a primary disease of muscle rather than nerve.

Laboratory workup sharpened the puzzle. Serum CPK, an enzyme released when muscle fibers break down, measured 900 IU/L against a reference ceiling of roughly 195 IU/L. Lactate dehydrogenase and inflammatory markers were also elevated, while a mild anemia hinted at systemic illness. Crucially, the team systematically excluded the usual suspects: antinuclear antibody, myositis-specific antibodies including anti-Jo-1, anti-Mi-2, anti-SRP, and anti-HMGCR were all negative, thyroid function and thyroid autoantibodies were normal, and testing for HIV, hepatitis B, and hepatitis C was negative. Epstein-Barr virus serology showed only evidence of past infection. No autoimmune, endocrine, toxic, or infectious explanation for the muscle injury survived scrutiny.

Electrophysiology added decisive detail. Electromyography recorded short-duration, low-amplitude motor unit potentials with early recruitment in the deltoid, first dorsal interosseous, and tensor fascia lata muscles, accompanied by prominent fibrillation potentials and positive sharp waves—a pattern characteristic of inflammatory or necrotizing myopathy. Nerve conduction studies were essentially normal, with only mild secondary axonal features, confirming that the problem lay in muscle itself rather than in the peripheral nerves supplying it. By this point, the differential diagnosis had narrowed to inflammatory myopathy, paraneoplastic myopathy, and metabolic muscle disease.

The turning point came from imaging. A contrast-enhanced computed tomography scan, obtained during the systemic evaluation, revealed enlarged left axillary lymph nodes measuring 3.5 by 2.4 centimeters along with an enlarged spleen, without focal lesions in the liver or spleen and without mass lesions elsewhere. These findings suggested a systemic lymphoproliferative process and prompted an excisional biopsy of the axillary node in April 2023. Histopathology showed complete effacement of the node’s architecture by a monomorphic population of medium-sized atypical lymphoid cells, studded with mitotic figures and interspersed tingible-body macrophages that produced the classic ‘starry-sky’ pattern—the histological signature of Burkitt lymphoma.

Immunohistochemistry sealed the diagnosis. The malignant cells expressed CD20, CD10, and BCL6, markers of a germinal-center B-cell origin, and the Ki-67 proliferation index approached 100 percent, reflecting the tumor’s hallmark near-maximal division rate. Cytogenetic analysis demonstrated rearrangement of the MYC oncogene, the molecular engine of Burkitt lymphoma. Staging studies—including bone marrow aspiration and biopsy, magnetic resonance imaging of the brain and entire spine, and cerebrospinal fluid cytology—found no marrow or central nervous system involvement, and the patient was classified as having Ann Arbor Stage III disease based on nodal involvement and splenomegaly.

One diagnostic step was deliberately sacrificed to time. Although muscle biopsy is generally considered the gold standard for classifying inflammatory myopathies, the team deferred the procedure because Burkitt lymphoma is among the most rapidly proliferative of all human malignancies, with tumor doubling times measured in days, and any delay in chemotherapy could prove catastrophic. Corticosteroids, notably, had not been given before the onset of weakness or the initial electrodiagnostic studies, ruling out the common confounder of steroid-induced myopathy; they entered the picture only afterward as part of treatment. The diagnosis of probable paraneoplastic myopathy therefore rested on the convergence of clinical findings, electrophysiology, exclusion of alternatives, and—most persuasively—what happened next.

What happened next was a striking, temporally coupled recovery. The patient began intensive therapy with the Hyper-CVAD regimen, alternating courses of cyclophosphamide, vincristine, doxorubicin, and dexamethasone with high-dose methotrexate and cytarabine, combined with rituximab targeting the CD20 antigen and standard central nervous system prophylaxis. After just the first cycle, by May 2023, his muscle strength had improved markedly and serum CPK had fallen from 900 to approximately 400 IU/L. By August 2023, upon completion of the full treatment course, CPK had normalized to 150 IU/L. Follow-up electromyography in September 2023 showed complete resolution of the previously documented myopathic abnormalities—normalized spontaneous activity, motor unit morphology, and recruitment patterns—confirmed by independent review by an experienced neurologist. At his most recent follow-up in March 2026, the patient remained asymptomatic with normal strength and no recurrence of muscle symptoms.

The clinical lesson embedded in this case concerns the phenomenon of paraneoplastic neuromuscular syndromes, in which the immune system’s response to an occult tumor spills over into attack on healthy tissue. Paraneoplastic myopathies are well described alongside solid tumors and certain hematologic malignancies, particularly Hodgkin lymphoma and intravascular large B-cell lymphoma, but their appearance ahead of sporadic Burkitt lymphoma in an immunocompetent adult appears to be exceptionally rare. Proposed mechanisms include cytokine-driven inflammation, molecular mimicry between tumor antigens and skeletal muscle proteins, and broader immune dysregulation orchestrated by the malignancy. These processes can injure muscle before any constitutional symptom, mass effect, or abnormal blood count announces the cancer, making early diagnosis genuinely difficult.

The case also distinguishes itself from prior reports of Burkitt lymphoma touching the nervous system. Earlier publications described paraplegia from spinal epidural disease, Guillain-Barré syndrome, bilateral numb chin syndrome, and oculomotor nerve palsy—all reflecting direct tumor infiltration or cranial and meningeal involvement. This patient, by contrast, had no cranial neuropathy, no sensory deficit, no cerebrospinal fluid malignant cells, and no marrow disease; electromyography pointed squarely at muscle. The neuromuscular symptoms were not a complication of advanced lymphoma but the principal reason he sought care at all. The authors acknowledge the limitations inherent in a single case report without histological confirmation of muscle involvement and with a restricted immunohistochemical panel, but argue that the full constellation of evidence strongly favors an indirect immune-mediated process tied to the lymphoma.

For clinicians, the message is pragmatic: unexplained proximal muscle weakness with elevated CPK should not be reflexively attributed to primary inflammatory myopathy when conventional investigations come back unrevealing. A careful systemic evaluation, including assessment for occult malignancy, may be warranted in atypical cases—and time matters, because Burkitt lymphoma, while ferociously aggressive, is also among the most chemosensitive cancers known. Early recognition of rare paraneoplastic presentations may mean the difference between timely, curative therapy and a fatal delay. In this instance, treating the cancer cured the muscle disease, a sequence that underscores both the diagnostic value of listening carefully to unusual symptoms and the intricate, sometimes treacherous dialogue between tumors and the immune system.

Subject of Research: Paraneoplastic myopathy as the initial presentation of sporadic Burkitt lymphoma in an immunocompetent adult

Article Title: Paraneoplastic Myopathy as a Possible Initial Presentation of Sporadic Burkitt Lymphoma in an Immunocompetent Adult: A Case Report

Article References: Khalafi‐Nezhad, A., Firouzabadi, D., mohammadkarimi, V., & Dehghanian, A. (2026). Paraneoplastic Myopathy as a Possible Initial Presentation of Sporadic Burkitt Lymphoma in an Immunocompetent Adult: A Case Report. Cancer Reports, 9(9), Article e70669. https://doi.org/10.1002/cnr2.70669

Image Credits: AI Generated

DOI: 10.1002/cnr2.70669

Keywords: Burkitt lymphoma, paraneoplastic myopathy, creatine phosphokinase, electromyography, Hyper-CVAD, MYC rearrangement, non-Hodgkin lymphoma, muscle weakness, case report, immune-mediated myopathy, oncology, neuromuscular disease