Rare Skin Nodules Reveal Hidden Lymphoma in Unusual Case Report

A rare and diagnostically challenging presentation of angioimmunoblastic T-cell lymphoma (AITL) has been documented in a new case report published in Pathology and Oncology Research, describing a 53-year-old man whose only initial symptom was multiple painless subcutaneous nodules spread across his trunk and upper limbs. The report, led by pathologists at Sanya Central Hospital in Hainan Province, China, together with Inner Mongolia Medical University, highlights how this aggressive lymphoma can masquerade as far more common skin conditions, delaying diagnosis in patients whose disease may already be at an advanced stage.

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