Anaplastic Lymphoma Kinase (ALK)-Negative Anaplastic Large Cell Non-Hodgkin Lymphoma as a Rare Differential Diagnosis of Lung Cancer: A Case Report

Abstract

Anaplastic large cell lymphomas (ALCL) are a group of sporadic malignancies that generally have an aggressive clinical course, especially the subtype of anaplastic lymphoma kinase (ALK)-negative ALCL. The appropriate diagnostic study modalities must be chosen to make an accurate diagnosis and promptly initiate specific treatment. We present the clinical case of a 72-year-old male patient with dyspnea on small efforts accompanied by diaphoresis and a weight loss of 10 kg in two months. Physical examination revealed adenopathy in the cervical region and bilateral pleural effusion. The pleural and lung biopsies revealed poorly differentiated metastatic adenocarcinomas. A multidisciplinary analysis was carried out; the typical clinical-radiographic presentation of adenocarcinoma was ruled out with immunohistochemistry, thus determining a diagnosis of ALK-negative anaplastic large cell non-Hodgkin's lymphoma. This case represented a diagnostic and therapeutic challenge since it is a rare entity with a poor prognosis, and there are only a few studies about the choice of appropriate chemotherapy in these patients.

Keywords: anaplastic large cell lymphoma (alcl); anaplastic lymphoma kinase (alk); cd30; mature t-cell lymphoma; peripheral t-cell lymphoma; poorly differentiated lung adenocarcinoma.

Figure 1. Chest X-ray at admission

Upon admission, the chest x-ray revealed the presence of pleural effusion that was bilateral with a right-sided predominance (black arrow).

Figure 2. Simple chest CT conducted after thoracentesis with the mediastinal window setting

A: The presence of lymphadenopathy is seen in regions 2R (a) and 2L (b), as well as bilateral pleural effusion; B: Lymph nodes in regions 5 (c) and 6 (d); C: Adenopathy in region 7 (e) and bilateral pleural effusion; D: Ground glass (*) seen in the left axial interstitium of the subpleural region

Figure 3. Lung parenchyma biopsy stained with H&E (40x)

a: Neoplastic cells of epithelial origin of intermediate size, with moderate cytoplasm and large, hyperchromatic nuclei; b: Atypical mitotic figures These cells are arranged diffusely in nests and form poorly differentiated glandular structures. These neoplastic cells are also diffusely observed in nests and form glandular structures in the pleura and lymph nodes. H&E: Hematoxylin and eosin

Figure 4. Lung parenchyma biopsy stained with H&E (400x)

The histopathological examination showed a lymphoid proliferation consisting of large cells that exhibit cytoplasmic abundance featuring a centrally located nucleus of open chromatin that assumes a kidney-shaped configuration (a). These cells were observed to rest on a reactive background comprised of mature lymphocytes, abundant eosinophils, and macrophages. These features were also observed in the pleura and mediastinal nodes. H&E: Hematoxylin and eosin

Figure 5. Positive immunostaining lung parenchyma biopsy indicating ALCL (40x)

A: Positive staining for CD30; B: Positive staining for EMA, C: Positive staining for CD43. The presence of CD30 indicates the activation of the lymphoma cells, while EMA and CD43 are characteristic markers of ALCL. ALCL: Anaplastic large cell lymphomas, EMA: Epithelial membrane antigen

Figure 6. Characteristics of ALK-negative ALCL

ALK: Anaplastic lymphoma kinase; ALCL: Anaplastic large cell lymphomas; IPI: International prognostic index; EMA: Epithelial membrane antigen; LDH: Lactate dehydrogenase. Image created with BioRender.com (Science Suite Inc., Toronto, ON, CAN).