Anaplastic large cell lymphoma (ALCL) is a rare subtype of mature T-cell lymphomas that are CD30 positive and may present with or without the aberrant expression of the anaplastic lymphoma kinase (ALK) protein. While, like most lymphomas, most ALCL cases are detected in lymph nodes, cases have been reported in sites outside lymph nodes, which are rare. The malignancy may present with a variety of symptoms which may lead to it being missed while diagnosing. We present a unique case of ALK-positive ALCL of the knee joint.

A 51-year-old female presented with pain in her right knee joint in March 2022 to an outside institution. The pain was insidious hematolymphoid malignancy. She was diagnosed with Stage II ALK+ ALCL of the knee joint. She was taken up for treatment that was based on the NCCN treatment guidelines for ALK-positive ALCL. She received 6 cycles of a multiagent chemotherapy regimen consisting of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone. A PET-CT scan was done for interim restaging after the chemotherapy that showed a near-complete resolution (with a standardized uptake value of 3.4) of the lesion in the knee joint. This is followed by involved-site radiotherapy (ISRT) with a cumulative dose of 45 Gy in 25 fractions (36 Gy in 20 fractions to the initial volume before the chemotherapy followed by a boost of 9 Gy in 5 fractions to the residual lesion post-chemotherapy). Follow-up showed complete resolution of the symptoms. The latest PET scan 1 year since the treatment began showed resolution of the lesion.

ALCL, like other lymphomas, is most commonly seen in the lymph nodes. It is more often seen in children as compared to adults [1, 2] Extranodal sites for its occurrence include the skin, bones, soft tissues, and lungs ^[3]. In the postoperative setting, ALCL is commonly found in breast implants ^[4]. In the knee joint ALCL is a rare entity. Among lymphomas that occur in the knee, B-cell lymphomas are more common. In patients with knee prosthesis lymphomas are rare, and among ALCL cases only ALK-negative variants have been documented ^[5]. Among bony ALCL cases, common sites include the iliac bones ^[6], the sternum ^[7], the proximal femur ^[8], vertebrae, and ribs [9, 10,11]. Primary non-Hodgkin’s lymphoma of the knee joint has also been reported, and in rare cases, it has been found to involve the synovium ^[12]. Cases of an ALCL primarily of the knee joint have not been observed. ALCL has been documented to present with a wide variety of symptoms that makes cases with extranodal sites as the primary location hard to diagnose. There are cases reported with patients presenting with fever, malaise, weakness, loss of appetite, and weight loss ^[13]. Bony lesions present with pain on movement and may be picked up on the scan as a lytic lesion. Differential diagnoses, especially considering the age of the patient, generally constitute diseases of infectious etiology such as osteomyelitis, synovitis, septic arthritis, or tuberculosis. ALCL is also known to present as arthritis even when the site of the primary lesion is away from the symptomatic bones or joints ^[14]. ALK-positive ALCL is shown to have better prognostic outcomes as compared to ALK-negative ALCL. Aggressive treatment with brentuximab vedotin, which is a CD30-directed antibody, combined with cyclophosphamide, vincristine, and doxorubicin is chosen as the first line of treatment. Brentuximab vedotin-based chemotherapy regimens have shown to have 97% complete response rate after 6 cycles ^[15]. The latest NCCN guidelines suggest the use of BV-CHP as the first line of treatment in ALK-positive ALCL. In-field radiotherapy (IFRT) and ISRT are two techniques used to deliver radiation to consolidate the action of chemotherapy in lymphomas. IFRT, which delivers radiotherapy to all the lymph nodes in a given set of anatomical boundaries, has now been replaced with ISRT which delivers radiation to the involved lymph nodes and sites only. Extranodal lymphomas are seen respecting as well as violating anatomical boundaries on imaging which poses a challenge in determining the extent of the target volume. Strict guidelines do not exist to treat these malignancies ^[16]. Most lymphomas are treated with a dose ranging from 30 to 36 Gy at 1.8–2 Gy per fraction. About 30–36 Gy is also accepted for aggressive extranodal lymphomas with complete response to systemic therapy. An additional dose may be added to compound the total delivered dose to 40–45 Gy in the same fractionation schedule in cases of partial response, recurrence, or treatment failure ^[17]. We chose the higher total dose in our patient in view of the aggressive nature of the malignancy and the low residual uptake (SUV 3.4) seen in the restaging PET-CT scan.

Extranodal ALCL is an aggressive disease that is commonly misdiagnosed and may pose a challenge to treat if not detected early. Any lesions that fail to respond to initial lines of management for the probable should be promptly tested for malignancies to rule them out. As can be seen in this case, ALCL can occur in unexpected sites and timely initiation of treatment can limit the morbidity caused by it.

During the course of this patient’s workup, neoplastic disorders and infectious diseases, both common and rare, should be closely examined. A histological analysis is essential in these circumstances. As demonstrated in this instance, ALCL can develop in unanticipated locations, and swift intervention may mitigate the damage.