A Case Report of Primary Pulmonary Lymphoepithelioma-Like Carcinoma with "Harmful" Pseudoprogression and a Pathological Complete Response (pCR) after Immunotherapy Plus Radiotherapy.

[BACKGROUND] Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of primary non-small cell lung cancer (NSCLC), with no established treatment guidelines. We present a case of a young female with PPLELC who achieved a pathological complete response (pCR) in both primary and metastatic lesions after receiving combined immunotherapy and radiotherapy.

[CASE DESCRIPTION] We present a 33-year-old female patient with stage IVa (cT2bN0M1b) PPLELC. As a first-line treatment, the patient received seven cycles of nab-paclitaxel combined with toripalimab (a PD-1 inhibitor) and achieved stable disease. This was followed by toripalimab maintenance therapy for nearly 30 months. During toripalimab maintenance therapy, the patient demonstrated slight enlargement of both lung lesions and brain lesions. Radiotherapy was subsequently administered to both locations. However, after radiotherapy, the patient exhibited radiographic progression in both lesions with associated worsening of clinical symptoms. Surgical resection of the localized lesions was clinically warranted. Unexpectedly, the final postoperative pathology revealed a pCR. The patient maintained progression-free survival (PFS) exceeding 70 months, confirming that the prior radiographic progression represented pseudoprogression. Pseudoprogression is commonly defined as radiologic tumor progression from baseline that is not confirmed as progression on subsequent radiologic evaluation. Most of the patients experiencing pseudoprogression had a good performance status (PS), were paucisymptomatic, and even experienced the improvement of tumoral symptoms. In contrast, our case presented with worsening clinical symptoms and general conditions, which we term "harmful" pseudoprogression. To our knowledge, such a case of PPLELC with a "harmful" pseudoprogression is rarely reported; moreover, the term "harmful" pseudoprogression is our original creation.

[CONCLUSION] Our case highlights the critical role of re-biopsy and re-evaluation of imaging criteria in assessing the response to immunotherapy.