AITL is an aggressive subtype of peripheral T-cell lymphoma derived from T-follicular helper cells, accounting for roughly 2 percent of all non-Hodgkin lymphomas and 15 to 20 percent of peripheral T-cell lymphomas. It is characterized by prominent inflammatory and immune dysregulation, with typical clinical features including lymphadenopathy, B symptoms such as fever, night sweats and weight loss, and hypergammaglobulinemia. Additional features may include anemia, hemolysis and hepatosplenomegaly. Skin involvement occurs in approximately half of all AITL patients, but it usually takes the form of rash or pruritus, which is frequently misdiagnosed as a drug eruption or viral exanthem. AITL presenting primarily with multiple subcutaneous nodules, without any of these more typical cutaneous signs, is exceedingly rare.

The patient in this case first noticed nodules on his back one month before seeking medical attention in September 2025, after which the lesions spread to his trunk and upper limbs. He denied any pruritus or pain and reported no fever, night sweats or weight loss. He also had no history of tuberculosis, hepatitis, leprosy or other infectious diseases. On physical examination, clinicians observed multiple subcutaneous nodules measuring approximately 0.5 to 2 centimeters in diameter on the back, chest, abdomen and upper limbs. The nodules were moderately firm, non-tender and covered by dark red infiltrative plaques, without ulceration or purulent discharge.

Laboratory investigations revealed mild anemia, with a hemoglobin level of 112 g/L, along with mildly elevated inflammatory markers, including C-reactive protein at 18 mg/L and an erythrocyte sedimentation rate of 35 mm/h. Serum immunoglobulin analysis showed decreased IgA at 0.86 g/L and elevated total serum IgE at 198.25 IU/mL, while IgM and IgG levels remained within normal ranges. Autoimmune and infectious screening, including antinuclear antibody, extractable nuclear antigen antibody, antineutrophil cytoplasmic antibody, Epstein-Barr virus, HIV and treponema pallidum tests, were all negative. Computed tomography imaging then revealed multiple mildly enlarged mediastinal lymph nodes, with the largest measuring approximately 20 mm in short-axis diameter, as well as widespread lymphadenopathy in the cervical, supraclavicular, axillary, mediastinal, retroperitoneal, pelvic and inguinal regions.

The diagnostic breakthrough came from histopathological examination of an excisional biopsy specimen taken from the left inguinal lymph node and from the subcutaneous nodules themselves. Pathologists found that the normal architecture of the lymph node was completely interrupted, with destruction of the germinal centers and an absent mantle zone. CD21 immunohistochemistry demonstrated disruption of the follicular dendritic cell meshwork within the lymph node, showing a branching and wind-swept pattern. There was marked proliferation of high endothelial venules with a branching pattern and endothelial cell swelling, along with basement membrane-like material deposition in the vessel walls and stroma. In the paracortical region and around blood vessels, a relatively diffuse infiltration of neoplastic T cells with clear cytoplasm was observed.

Immunohistochemical analysis proved positive for CD3, CD4, CD5, CD10, CXCL13 and Ki67 at 40 percent, while staining for CD20, CK-pan and CD8 was negative. In situ hybridization for EBV-encoded RNA was positive in scattered cells. Critically, the subcutaneous nodules yielded immunophenotypic findings similar to those seen in the lymph node, including consistent expression of PD-1 and CXCL13 in both sites. Based on these histopathological and immunohistochemical examinations, a diagnosis of AITL was finally established, and the patient was transferred to the hematology department of another hospital for further treatment. Pathological review at the referring institution confirmed the diagnosis, classified as Ann Arbor stage III.

To place this case in context, the authors conducted a literature review of rare cutaneous presentations of AITL. Previous reports have described dermatomyositis-like skin lesions in an elderly man who developed widespread erythematous papules over the extensor surfaces of the finger joints, shoulders and back, as well as a distinctive psoriasiform dermatitis with intermittent trailing scale. A case from Japan documented AITL manifesting as erythema multiforme with targetoid lesions and central bullae, while another described agminated miliary facial papules initially misdiagnosed as reactive B-cell hyperplasia. Other reported cutaneous manifestations include angioedema, prurigo-like lesions and linear IgA bullous dermatosis. The present case is noteworthy in that the initial presentation consisted of multiple subcutaneous nodules without pruritus or rash, posing a significant diagnostic challenge.

Several differential diagnoses were considered and systematically excluded. Leprosy was initially suspected because of the erythema nodosum-like skin lesions, but the typical clinical features such as nerve impairment or hair loss were absent. Connective tissue diseases, including systemic lupus erythematosus and dermatomyositis, were ruled out due to negative autoantibody results and the absence of systemic manifestations such as myalgia or arthritis. Subcutaneous nodules can also be associated with internal malignancies, including gastric or lung cancer, but the patient had no known history of primary malignancy and imaging did not reveal a primary tumor. Notably, cutaneous metastases typically present as firm, isolated nodules, whereas the diffuse infiltrative pattern observed in this case is rarely seen in metastatic disease.

The authors emphasize that cutaneous lesions in AITL may represent either reactive immune-mediated manifestations or true neoplastic infiltration secondary to systemic lymphoma involvement. Reactive lesions are thought to result from immune dysregulation and cytokine release, whereas neoplastic lesions usually demonstrate infiltration by TFH phenotype lymphoma cells and are often associated with systemic disease progression. In this case, the widespread lymphadenopathy, histopathological confirmation of AITL in the lymph node, and the similar immunophenotypic findings in both lymph node and subcutaneous lesions favored secondary cutaneous involvement by AITL rather than a purely reactive process. The authors acknowledge that the absence of molecular clonality analysis in the skin lesion remains a limitation of the study.

Treatment consisted of six cycles of chidamide plus CHOP chemotherapy, a regimen combining the oral histone deacetylase inhibitor chidamide with the conventional CHOP backbone. The patient achieved complete response, with complete resolution of the subcutaneous nodules and superficial lymphadenopathy, and remained free of recurrence at follow-up. Standard first-line treatment for AITL currently relies on CHOP or CHOEP-based regimens, achieving complete remission rates of approximately 40 to 60 percent, but relapse is frequent and the overall prognosis remains poor, with a five-year survival rate of approximately 30 to 40 percent. Several emerging therapeutic strategies, including anti-CD30 antibody conjugates, hypomethylating agents such as decitabine and PD-1 inhibitors, are being explored, though the authors caution that these agents should be used carefully in clinical practice as they may be associated with immune-related adverse events. The case broadens the recognized cutaneous spectrum of AITL and underscores the importance of considering lymphoma in the differential diagnosis of unexplained subcutaneous nodules.

Subject of Research: A rare presentation of angioimmunoblastic T-cell lymphoma with multiple subcutaneous nodules as the primary cutaneous manifestation

Article Title: Multiple subcutaneous nodules as the primary presentation of angioimmunoblastic T-cell lymphoma: a case report and literature review

Article References: Li, Y., Cai, Y., & Xu, X. (2026). Multiple subcutaneous nodules as the primary presentation of angioimmunoblastic T-cell lymphoma: a case report and literature review. Pathology & Oncology Research, 32, Article 1612446. https://doi.org/10.3389/pore.2026.1612446

Image Credits: AI Generated

DOI: 10.3389/pore.2026.1612446

Keywords: angioimmunoblastic T-cell lymphoma, subcutaneous nodules, cutaneous manifestations, peripheral T-cell lymphoma, case report, immunohistochemistry, CHOP chemotherapy, chidamide, lymphadenopathy, differential diagnosis, T-follicular helper cells, Epstein-Barr virus

The research, published in the renowned journal BMC Cancer, meticulously reviewed medical records from two key oncology centers in Saudi Arabia, encompassing data from 99 patients diagnosed with PTCL. The average age of the cohort was 50.7 years, a statistic that is noteworthy because it highlights a relatively younger age at diagnosis compared to PTCL epidemiology in Western and other Asian populations. This demographic nuance raises provocative questions about genetic, environmental, or socioeconomic factors that may be uniquely influencing lymphoma presentation in Saudi Arabia.

Histopathological examination revealed that peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) constituted approximately 38.4% of cases, making it the most prevalent subtype within this cohort. Close behind was the ALK-negative anaplastic large cell lymphoma (ALK-ALCL), accounting for 26.3%. The prominence of these subtypes underscores the necessity to tailor therapeutic strategies that specifically address the biological traits of these lymphoma categories, which often differ dramatically in behavior and response to treatment.

A disturbing discovery from the study was that a significant majority of patients (60.6%) presented with advanced disease classified as Ann Arbor Stage IV. Coupled with this, over half the patients exhibited an International Prognostic Index (IPI) score of 3 or higher, indicating high-risk disease. These factors collectively paint a grim picture of PTCL detection timing and suggest systemic barriers to early diagnosis and intervention in the region.

The frontline treatment landscape appeared fragmented, with only about 32.3% of patients receiving combination chemotherapy as initial therapy. Furthermore, autologous stem cell transplantation (ASCT), often considered a cornerstone for consolidation in PTCL, was employed in a scant 14.1% of cases. Radiation therapy usage was similarly low, with just 13.1% of patients undergoing this modality as part of first-line treatment. Such undertreatment or deviation from global guidelines likely contributes to poor clinical outcomes reported in the study.

Survival analysis revealed disheartening results: the five-year progression-free survival (PFS) rate stood at merely 23.6%, while overall survival (OS) was 44%. These survival outcomes starkly contrast with data from Western cohorts, reinforcing the aggressive nature of PTCL in the Saudi Arabian population coupled with treatment limitations. Notably, statistical significance was detected when comparing survival across different treatment regimens, emphasizing that therapeutic strategy profoundly influences patient prognosis.

Multivariate analysis identified older age as an independent predictor of worse progression-free survival, with a hazard ratio of 1.03 per advancing year. This age-related risk accentuates the biological complexity and decreased treatment tolerance in elderly patients, which complicates management decisions. Additionally, the presence of B-symptoms—fever, night sweats, and weight loss—and extranodal disease involvement emerged as significant independent predictors of poorer overall survival, highlighting the importance of systemic symptomatology and tumor dissemination in disease progression.

The authors of the study draw attention to the pressing need for standardized diagnostic protocols and treatment pathways within Saudi Arabia. The current heterogeneity in management approaches leads to suboptimal outcomes and likely contributes to the disproportionately advanced disease stages at presentation. Early diagnosis, multidisciplinary care coordination, and adherence to evidence-based guidelines could dramatically improve survival metrics.

This retrospective analysis also implicates healthcare infrastructure and awareness as pivotal factors. Delayed referrals to oncology specialists and limited access to cutting-edge therapeutic options may be underlying contributors to the observed survival disparities. The research advocates for policy-level interventions, encompassing increased educational efforts targeting primary care providers and investment in oncologic resources.

Impressively, this study represents a landmark attempt to map the epidemiological and clinical contours of PTCL within the Middle East, a region underrepresented in global lymphoma research. The insights gained provide a foundation for future prospective studies designed to explore novel therapies, including targeted agents and immunotherapies, which hold promise in altering the dismal prognosis associated with PTCL.

Moreover, given the younger age at diagnosis and high-risk features elucidated, there is an implication that genetic or environmental factors unique to the Saudi population might modulate disease biology. Future translational research, incorporating genomic and proteomic profiling, could unravel these mechanisms, paving the way for precision medicine tailored to regional patient populations.

The study’s limitations, including its retrospective nature and the relatively small sample size, are duly acknowledged; nevertheless, its findings are compelling and underscore a critical gap in the current oncologic landscape. There is an urgent call for national cancer registries and prospective clinical trials to validate and build upon the present findings.

In summation, this landmark 12-year analysis exposes the stark realities faced by PTCL patients in Saudi Arabia — younger presentation, advanced staging at diagnosis, treatment heterogeneity, and poor survival outcomes. These findings implore the global oncology community to collaborate in developing and disseminating standardized, effective treatment regimens tailored to this unique population. Only through such concerted efforts can the dismal survival statistics be improved and hope be restored for patients grappling with this formidable hematologic malignancy.

Subject of Research: Peripheral T-cell lymphoma (PTCL) characteristics, treatment patterns, and survival outcomes in Saudi Arabia

Article Title: Treatment patterns and survival outcomes of peripheral T-Cell lymphoma in Saudi Arabia: a 12-Year retrospective analysis

Article References:
Al-Mansour, M., Alghanmi, H.A., Shareef, D.E. et al. Treatment patterns and survival outcomes of peripheral T-Cell lymphoma in Saudi Arabia: a 12-Year retrospective analysis. BMC Cancer 25, 1361 (2025). https://doi.org/10.1186/s12885-025-14793-7

Image Credits: Scienmag.com

DOI: https://doi.org/10.1186/s12885-025-14793-7