Primary ALK-Negative Anaplastic Large Cell Lymphoma Mimicking Septic Arthritis in a Diabetic Patient: Diagnostic and Therapeutic Challenges

Summary

Primary anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) originating in the knee was initially misdiagnosed as septic arthritis. Despite the patient's critical condition, a stepwise multidisciplinary treatment strategy resulted in recovery, emphasizing the need to consider lymphoma in atypical joint presentations.

Abstract

Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a rare, aggressive subtype of peripheral T-cell lymphoma that frequently presents with atypical features, creating substantial diagnostic challenges. Primary ALK-negative ALCL arising from the knee joint is exceptionally uncommon. This report describes a patient who was initially misdiagnosed with septic arthritis of the knee due to localized pain, swelling, and erythema. The delayed diagnosis illustrates the difficulty of distinguishing hematologic malignancies from common infectious conditions, particularly in immunocompromised individuals. At the time of diagnosis, the disease was at an advanced stage IVB and complicated by septicemia, septic shock, and pneumonia, limiting tolerance for intensive chemotherapy. A carefully staged treatment plan was employed, beginning with corticosteroids and etoposide, followed by liposomal mitoxantrone and the CD30-targeted antibody-drug conjugate brentuximab vedotin. This multidisciplinary approach led to clinical stabilization, recovery from critical illness, and eventual discharge, with ongoing hematologic follow-up. The clinical course highlights the necessity of maintaining a high index of suspicion for lymphoma in refractory joint infections and demonstrates that individualized, stepwise therapy can achieve remission even in critically ill patients with aggressive ALCL. These findings provide valuable insights for improving the diagnosis and management of lymphoma cases that mimic infectious diseases.

Introduction

Anaplastic large cell lymphoma (ALCL) is a mature T-cell malignancy characterized by large pleomorphic "hallmark" cells, typically exhibiting horseshoe or kidney-shaped nuclei and abundant cytoplasm, and by strong, uniform CD30 expression^1,2. ALCL is classified into anaplastic lymphoma kinase (ALK)-positive and ALK-negative subtypes, each representing approximately half of all cases^3,4. The 5th edition of the World Health Organization Classification of Tumors of Hematolymphoid Tissues (WHO-HAEM5) and the 2022 International Consensus Classificat....

Protocol

This study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital of Zhejiang University School of Medicine (Approval No. 2024-0844). All procedures were conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from the patient prior to participation.

1. Initial presentation, diagnosis, and treatment plan

1. Patient presentation: A 56-year-old male presented with a 3-month history of progressive swelling, pain, redness, and restricted motion in the left knee.
2. Physical examination: On arrival at the emergency department, the patient....

Results

With chemotherapy, intensive care, and antimicrobial therapy, the patient's condition improved significantly. He regained consciousness, the infection resolved, body temperature normalized (36.8 °C), and oxygenation stabilized (PaO₂/FiO₂ > 300) (Table 1). Inflammatory markers decreased substantially (CRP: 2.0 mg/L; PCT: 0.05ng/mL), serum LDH returned to within normal limits (187 U/L), and white blood cell count normalized (9.6 × 10⁹/L) (Tabl.......

Discussion

Diabetes mellitus (DM) is a life-limiting condition. Poorly controlled hyperglycemia impairs systemic immunity through multiple mechanisms, weakening skin defenses and substantially increasing the risk of skin and soft tissue infections, including cellulitis, osteomyelitis, and postoperative wound infections^20,21. These infections often necessitate surgical intervention, and in some cases, emergency surgery^13,1.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
5% Glucose Injection	commercially available	none	none
Brentuximab Vedotin for Injection	Takeda Pharmaceutical Company Limited	https://www.ema.europa.eu/en/ documents/product-information/ entyvio-epar-product-information_en.pdf
Dexamethasone Sodium Phosphate Injection	Hainan Beite Pharmaceutical Co., Ltd.	https://www.nmpa.gov.cn/data search/search-info.html?nmp a=aWQ9ZjI0M2FhZjU1NTFjZ DE0NDJlZDFiNWUyMGNmN TQzYzEmaXRlbUlkPWZmOD A4MDgxODNjYWQ3NTAwMT g0MDg4MWY4NDgxNzlm
Daptomycin for Injection	Cubist Pharmaceuticals, Inc.	https://www.merck.com/ product/usa/pi_circulars/c/ cubicin/cubicin_pi.pdf
Etoposide Injection	Qilu Pharmaceutical	https://www.qilu-pharma. com/products_details/137.html
Hydrogen Peroxide Solution	commercially available	none	3% v/v
Linezolid and Glucose Injection	Pfizer Investment CO.,Ltd	https://www.pfizer.com/products /product-detail/zyvox
Mitoxantrone Hydrochloride Liposome Injection	Zhongnuo Pharmaceutical (Shijiazhuang) Co. Ltd	https://doc.irasia.com/listco/hk /cspc/announcement/a220111.pdf
Meropenem for Injection	Luoxin Pharmaceuticals Group Stock Co., Ltd.	(96036-03-2)  https://www.luoxin .cn/page.aspx?node=111&utm ; https://www.nmpa.gov.cn/data search/search-info.html?nmpa= aWQ9YmU0YzJiOTgzZDRiZGI wZmY3MWUxMzE0NzdjMjY0Nj kmaXRlbUlkPWZmODA4MDgx ODNjYWQ3NTAwMTg0MDg4M WY4NDgxNzlm
Piperacillin Sodium and Tazobactam Sodium for Injection	Reyoung Pharmaceutical Co., Ltd.	https://www.reyoung.com/ attachment/cms/item/2020 _04/20_15/Product%20list% 20of%20Reyoung.pdf
Povidone-Iodine Solution	commercially available	none	1% v/v
Recombinant Human Granulocyte Colony-stimulating Factor Injection	Qilu Pharmaceutical Co., Ltd.	https://en.qilu-pharma.com /products_list/1.html
Sodium Chloride Injection	Hangzhou Minsheng Pharmaceutical Co., Ltd.	https://www.nmpa.gov.cn/ datasearch/search-info.html ?nmpa=aWQ9NzAxODhhYm QzODljZGNmMTlmNTM3Zjg 0NWIxZWRiM2MmaXRlbUlkP WZmODA4MDgxODNjYWQ3 NTAwMTg0MDg4MWY4NDgxNzlm
Vancomycin Hydrochloride for Injection	Zhejiang Medicine Co., Ltd. Xinchang Pharmaceutical Factory	https://www.zmc.top/en/product /detail/68.html; https://www. nmpa.gov.cn/datasearch/search- info.html?nmpa=aWQ9YmV iMzlhNzJmOGM1ODVmOGU3 YjQ1NmY4ZjI4YzJmMWQmaX RlbUlkPWZmODA4MDgxODNj YWQ3NTAwMTg0MDg4MWY4 NDgxNzlm