Pyothorax-associated Lymphoma: a Case Report and Review


 Background: Pyothorax-associated lymphoma is a rare disease with variations in endemic prevalence. PAL arising from a posttraumatic empyema are a rare occurrence.Case presentation: a male patient, 83 years old. Twenty years earlier, the patient fell from a height, sustaining a fracture to the right rib, which improved after conservative treatment. In September 2018, the patient had right chest pain (ribs 9–10). In February 2019, the chest pain became worse during sleep. CT examination showed inflammation of the right lower lobe, chronic empyema on the right with subdiaphragmatic infection, fibrosis of the right lung, atherosclerosis, thickening of the left pleura with rib destruction, and membranous calcification around the lesion. After 5 days of treatment with cefoperazone, sulbactam sodium, and ornidazole, the patient’s chest pain did not improve. The results of 18F-FDG PET/CT showed the following: a solid mass in the lower right thoracic cavity. Immunohistochemistry showed that the tumor cells were negative for CD20 and CD3, positive for background mature T lymphocytes, positive for Pax-5, positive for MUM-1, Ki-67 (70%, +); AE1/AE3, CD138, Bcl-6, CD10, CD5, CD56, MPO (-); CD79α (part +), EMA (part +), CD38 (+), bcl-2 (+). In situ hybridization (CISH): EBER+. Mini-CHOP chemotherapy was implemented on April 11, 2019. The patient stopped taking analgesics on the day of chemotherapy. The pain disappeared one week later, and the EBV-DNA fell to the normal range. In the later stage, the family members of the patient declined further patient treatment and reexamination. The patient’s condition worsened in July 2019 and he died on September 25, 2019.Conclusion: Pathological morphology is vital important to make a final diagnosis and avoid misdiagnosis or miss diagnosis. This case is described by a combination of imaging and pathological examinations that reports the clinical pathological diagnosis and treatment process of a single case of pyothorax-associated lymphoma, and it provides some diagnostic information regarding the rare disease of PAL.

Immunohistochemistry showed that the tumor cells were negative for CD20 and CD3, positive for background mature T lymphocytes, positive for Pax-5, positive for MUM-1, Ki-67 (70%, +); AE1/AE3, Conclusion: Pathological morphology is vital important to make a nal diagnosis and avoid misdiagnosis or miss diagnosis. This case is described by a combination of imaging and pathological examinations that reports the clinical pathological diagnosis and treatment process of a single case of pyothorax-associated lymphoma, and it provides some diagnostic information regarding the rare disease of PAL.

Background
Pyothorax-associated lymphoma (PAL) is a diffuse large B-cell lymphoma (DLBCL) of the non-Hodgkin's type originating from tuberculous pyothorax [1,2]. According to the current World Health Organization histological classi cation published in 2015 [3], PAL is classi ed as diffuse large B-cell lymphoma associated with chronic in ammation. Diffuse large B-cell lymphoma with chronic in ammation is a lymphoma involving long-term chronic in ammation and is closely associated with the Epstein-Barr virus (EBV). PAL is a prototype of diffuse large B-cell lymphoma with chronic in ammation. PAL was rst reported to have pathological and immunohistochemical features of a diffuse large B-cell lymphoma (DLBCL) in 1987 [4]. Because its clinical manifestations and imaging features are not typical, the diagnosis of PAL is very di cult. PAL is more common in patients with tuberculosis or tuberculous pleurisy controlled by arti cial pneumothorax. These patients usually have 22-to 30-year histories of pyothorax. Here, we describe a case of pyothorax-associated lymphoma in a male patient. He had a chest injury caused by trauma sustained 20 years earlier and a history of empyema one year earlier. Combining imaging and pathological examinations to describe the case, using mini-CHOP chemotherapy for one course, the effect was obvious. However, the patient's family decided to discontinue treatment, and the patient died ve months later. We analyzed the diagnosis and treatment process of PAL and summarized the evidentiary clues for the diagnosis of PAL, which provides valuable treatment experience.

Case Report
We present a male patient, 83 years old, with a history of diabetes going back more than 20 years, with controllable blood sugar. Twenty years earlier, the patient fell from a height, sustaining a fracture to the right rib, which improved after conservative treatment. In September 2018, the patient had right chest pain (ribs 9-10), no fever, no shortness of breath after physical activity, and no discomfort such as dyspnea.
In February 2019, the chest pain became worse during sleep. CT examination showed in ammation of the right lower lobe, chronic empyema on the right with subdiaphragmatic infection, brosis of the right lung, atherosclerosis, thickening of the left pleura ( Fig. 1a) with rib destruction, and membranous calci cation around the lesion (Fig. 1b). Physical examination showed that the super cial lymph nodes throughout the body did not touch the swollen area. Each segment of the left and right calves touched a circular subcutaneous nodule of 2 cm × 2 cm and 1 cm × 3 cm, respectively, with multiple skin lesions on the surface, itching, no purulence, and no tenderness. After 5 days of treatment with cefoperazone, sulbactam sodium, and ornidazole, the patient's chest pain did not improve. He was admitted to our hospital on April 4, 2019 for further diagnosis and treatment. At the time of admittance, he still had chest pain and discomfort on his right side. During his illness, he lost approximately 5 kg of weight.
The results of 18F-FDG PET/CT showed the following (Fig. 2): a solid mass in the lower right thoracic cavity; FDG metabolism increased periodically (SUVmax 18.0) in a manner consistent with lymphoma manifestations; the right lower lobe was swollen with in ammation, and the right pleura was thickened with calci cation; right pleural effusion, multiple in ammation of the right lung; mediastinum; and both hilar multiple lymphadenitis hyperplasia were enlarged.
According to the medical history, imaging examination, and pathological results, mini-CHOP chemotherapy was implemented on April 11, 2019. The patient stopped taking analgesics on the day of chemotherapy. The pain disappeared one week later, and the EBV-DNA fell to the normal range. In the later stage, the family members of the patient declined further patient treatment and reexamination. The patient's condition worsened in July 2019 and he died on September 25, 2019.

Discussion
PAL is a type of non-Hodgkin's lymphoma of mainly the B-cell phenotype. It develops in the pleural cavity in patients with longstanding histories of pyothorax. This disease was originally reported by Aozasa in 1987 and the term "pyothorax-associated lymphoma (PAL)" was proposed [4]. A nationwide study in Japan collected 37 cases of pleural lymphoma. The EBV genome was detected in lymphoma cells in all PAL by polymerase chain reaction, in situ hybridization, and immunohistochemistry. [5]. As early as 1993, Yamabe et al. [6] discovered that PAL is closely associated with EBV infection. Sorting out the reported literature indicates that the EBV genome is detectable in the lymphoma cells of most PAL cases [7,8].
The endemic prevalence of PAL is different in whole world. Due to the use of arti cial pneumothorax for the treatment of tuberculosis. PAL cases are most commonly reported in Japan. Nakatsuka et al. [1] reviewed clinical and pathological ndings in 106 patients with PAL in the age range of 46-82 years (median, 64 years) collected through a nationwide survey in Japan. A male/female ratio was 12.3:1. All patients had history of pyothorax caused by arti cial pneumothorax. In an situ hybridization study, 70% of patients were positive for Epstein-Barr virus (EBV).
Most cases of PAL develop from a pyothorax caused by an arti cial pneumothorax created during the treatment of pulmonary tuberculosis or tuberculous pleuritis, and it is attributed to chronic in ammation of the pleura. However, from the cases we have come into contact with, PAL has been shown not to be restricted to pulmonary tuberculosis or similar conditions; it can develop from any type of empyema. Taniguchi et al. [9] reported the rst case of PAL arising from a posttraumatic empyema. This case indicates that posttraumatic empyema could be a risk factor for the development of malignant lymphoma, and caution should be exercised to prevent chronic empyema when treating patients with chest injuries. Our case is also PAL arising from posttraumatic empyema. This patient was EBV-positive, as in most cases of PAL.
Another nding of interest was that the patient was CD20-negative. Consistent with our case, in the rst PAL patient with empyema after trauma, CD3 and CD20 of the primary tumor were negative. There have also been other case reports of CD20-negative PAL. Kenji Fukuno et al. [10] proposed that PAL probably originates from B cells, CD20 is then lost during B cell differentiation into plasma cells. Therefore some CD20-negative pyothorax-associated B cell lymphomas are expected.
PAL is mostly associated with underlying diseases. The imaging features of primary malignant lymphomas originating from the chest wall are the tumor spreading along the pleura, sometimes involving the ribs but mostly maintaining rib structure. However, lymphomas with similar features are also recognized in other chronic in ammatory conditions. PAL can be di cult to diagnose using imaging alone. This disease is occasionally misdiagnosed as lung cancer or a form of tuberculous abscess. Rare, empyema-associated malignant tumors and malignant tumors accompanied by empyema that should be Abbreviations PAL Pyothorax-associated lymphoma EBV Epstein-Barr virus Declarations Ethical Approval and Consent to participate Not applicable.

Consent for publication
Written informed consent was obtained from the patient for the publication of this case presentation.
Copies of the consent forms are available for review by the Editor of this journal.

Availability of data and materials
The dataset supporting the ndings and conclusions of this case report is included within the article.

Competing interests
No potential con ict of interest was reported by the authors. considered in the differential diagnosis of pyothorax-associated lymphoma [11]. Wan and Lan et al. [12] also pointed out the PAL needs to be differentiated from primary exudative lymphoma. Research has shown that speci c imaging features of pyothorax-associated lymphoma, such as symmetric growth pattern of a mass at the margin of chronic empyema appear to be distinct from other empyemaassociated malignant lesions [11]. In this case, CT examination revealed chronic empyema on the right side of the chest with subphrenic infection. The lesion protruded inward into the right lower lobe, adjacent to the diaphragm and liver compression, local thickening of the pleura not consistent with nodular calci cation. However, it is still not enough to con rm the diagnosis of PAL directly by imaging examination.
Therefore, pathological examination is particularly important to diagnosis. This case is described by a combination of imaging and pathological examinations that reports the clinical pathological diagnosis and treatment process of a single case of pyothorax-associated lymphoma, and it provides some diagnostic information regarding the rare disease of PAL. 12. Wang F, Lan H. A case report on the effect of rituximab on pyothorax-associated lymphoma.
Medicine. 2019;98:e18393-e. Figure 1 The results of CT examination showed (a) in ammation of the right lower lobe, chronic empyema on the right with subdiaphragmatic infection, brosis of the right lung, atherosclerosis, thickening of the left pleura, with (b) rib destruction, and membranous calci cation around the lesion.