Synchronous primary gastric diffuse large B-cell lymphoma and multiple lung primary adenocarcinoma with pulmonary cryptococosis: a case report and literature review

Abstract

Background

The coexistence of non-Hodgkin’s lymphoma of the stomach and multiple primary lung adenocarcinomas with pulmonary cryptococcosis has rarely been reported.

Case presentation

We herein present a 75-year-old man who was admitted to our hospital due to hematemesis. Gastroscopy and imaging revealed extensive stomach wall thickening and multiple lung lesions, including nodules and cavernous lesion. The patient was diagnosed with primary diffuse large B-cell lymphoma via gastroscopy and bilateral lung primary adenocarcinoma with cryptococcal infection via percutaneous CT-guided puncture biopsy. He subsequently underwent six cycles of R-CHOP regimen for gastric lymphoma, along with CT-guided radiofrequency ablation for the upper lobe of the right lung primary adenocarcinoma and radioactive particle implantation was performed on the lower lobe of the left lung primary adenocarcinoma, supplemented with antifungal therapy. After a definite diagnosis and systemic treatment, the patient was followed up for twenty-seven months with no tumor recurrence, progression or metastasis.

Conclusion

To the best of our knowledge, the complex combination of multiple primary malignancies and pulmonary cryptococcal infection is extremely rare. The diagnosis is been confusing and challenging. CT-guided needle biopsy can help achieve pathological diagnosis, elucidate the type and stage of the tumor, and even change the clinical treatment strategy, which is necessary and beneficial.

Background

The metachronous occurrence of other malignancies such as lung cancer in patients with non-Hodgkin’s lymphoma (NHL) during the clinical course is not necessary rare [1]. The coexistence of two separate primary malignancies, gastric NHL and lung adenocarcinoma, has rarely been reported. We herein present an extremely rare case of coincidental primary diffuse large B-cell gastric lymphoma, bilateral primary lung adenocarcinoma, and pulmonary cryptococcosis in an immunocompetent patient. To the best of our knowledge, this is the first case report of such coexistence.

Case presentation

A 75-year-old Chinese man was admitted to our hospital in June 2021 due to hematemesis. He did not have fever, nocturnal diaphoresis, or significant weight loss exceeding 10% within the preceding six months. The results of his physical examination were unremarkable. The patient had no history of smoking or malignancy. His abnormal laboratory findings on admission included hemoglobin level of 6.2 g/dL and positive occult blood in the feces. Leukocyte count and lymphocyte percentage were normal. He also tested negative for human immunodeficiency virus (HIV). Gastroscopy revealed a huge lesion, approximately 6 × 7 cm, with an irregular margin at the gastric body on the next day (Fig. 1A). Endoscopic biopsy revealed diffuse large B-cell lymphoma (DLBCL) (Fig. 1B). The diagnosis was further confirmed by immunohistochemistry; positive stains for CD20, CD45, CD79a, and bcl-6; and negative stains for CD3, CD10, and CK (pan). To further evaluate the extent of gastric lymphoma-surrounding invasion, contrast-enhanced CT scan of the whole abdomen was performed, and extensive gastric wall thickening with mild homogeneous enhancement was observed (Fig. 1C and D). Routine chest CT examination on admission revealed different types of nodules and a cavitary lesion in the lungs. These findings were initially concerning for metastatic disease, adding significantly to the diagnostic challenge in this case. Axial CT images showed a nodule measuring 1.5 × 1.5 cm in the upper lobe of the right lung (Fig. 2A), a ground-glass opacity (GGO) measuring 1 cm in the lower lobe of the left lung, and a cave-in lesion measuring 2.5 × 2.3 cm in the dorsal segment of the left lower lobe near the left oblique fissure (Fig. 2B and C). No significantly enlarged lymph nodes were observed in the mediastinum or bilateral hilum. As the three lesions with different imaging manifestations revealed, it was difficult to distinguish between metastatic tumors, primary lung tumors, tuberculosis, and other diseases in an elderly man who has just been diagnosed with gastric malignant tumor. CT-guided biopsies of the three lesions were separately performed. Lung nodule and GGO lesions were primary lung adenocarcinoma, the expression of EGFR positive (Fig. 2D) with positive mutation for EGFR (exon 21 L858R mutation). The cavitary lesion was proven to be Cryptococcus gattii infection (Fig. 2E). To correct staging, fluorine 18-labeled fluorodeoxyglucose-positron emission tomography-CT (PET-CT) and bone marrow biopsy were performed. PET-CT revealed an abnormal uptake in the gastric lesion and three lung lesions (Fig. 3A, B and C), whereas bone marrow biopsy was normal. Therefore, the patient was diagnosed with synchronous primary DLBCL, bilateral primary lung adenocarcinoma, and pulmonary cryptococcosis.

Fig. 1.

(A) Gastroscopy revealed a malignant lesion measuring approximately 6 × 7 cm at the gastric body. (B) Pathology of gastric lymphoma shows a large and enlarged allotypic lymphocyte infiltration. (hematoxylin and eosin staining, ×40). (C) Abdominal CT revealed diffuse gastric wall thickening. (D) The thickened wall exhibited minimal homogeneous enhancement

Fig. 2.

(A) Chest CT revealed an ill-defined nodule on the right upper lobe (↑). (B) Ground-glass opacity on the left lower lobe (↑). (C) Cavity close to the left interlobar fissure (↑). (D) Puncture tissue (CT-guided percutaneous needle biopsy specimens of the upper lobe of right lung nodule.) : invasive lung adenocarcinoma with acinar growth. (hematoxylin and eosin staining, ×40). (E) CT-guided percutaneous needle biopsy specimens of the cavity. At high magnification, more vacuolar transparent bodies can be seen in multinuclear giant cells, which is considered to be cryptococcal infection. (hematoxylin and eosin staining, ×40)

Fig. 3.

(A) ¹⁸F-FDG-PET/CT revealed extensive abnormal uptake in the gastric wall (SUV_max, 15). (B) ¹⁸F-FDG-PET/CT revealed an ill-defined nodule on the right upper lobe (SUV_max, 1). (C) ¹⁸F-FDG-PET/CT revealed GGO on the left lower lobe (SUV_max, 3) and a cavity close to the left interlobar fissure (SUV_max, 4.3)

According to the patient’s condition and own choice, an individualized treatment plan was made after comprehensive consideration. First, CT-guided radiofrequency ablation (RFA) of the right lung adenocarcinoma was performed. Three days later, ten radioactive particles were implanted into the left lung adenocarcinoma. Because the lesion was so close to the descending aorta, not suitable for using RFA therapy. The patient’s postintervention course was uneventful, and the patient underwent six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen. Furthermore, before and during chemotherapy, the patient was administered fluconazole for pulmonary cryptococcosis. As the lung adenocarcinoma was positive for EGFR mutation, gefitinib was recommended, but the patient declined due to financial reasons. If lung adenocarcinoma progresses and deteriorates in the future, molecular targeted drugs can be used as an alternative treatment. After a definite diagnosis and systemic treatment, the patient was followed up for twenty-seven months with no tumor recurrence, progression or metastasis.

Discussion and conclusions

The gastrointestinal tract is the most common extranodal site affected by NHL, accounting for about 50–60% of all extranodal cases [2], whereas the stomach is the most common gastrointestinal site (60–75%) [3]. Patients with NHL have a higher rate of secondary malignancy than the general population, and lung cancer is the most common type [4, 5], chemotherapy such as CHOP or CHOP-like regimen and radiotherapy should be accounted for it [1, 6, 7]. However, coexistence of primary lymphoma and primary lung cancer has rarely been reported. After an extensive literature search, only eleven other published cases were identified [8–18] (Table 1).

Table 1.

Synchronous malignant lymphoma and lung cancer in the literature

Year/ref.	Age /gender	Lung cancer	Malignant lymphoma	Treatment	Outcome	Survival time (months)
1999/[8]	71/F	SCC	TCL/lung	lobectomy + chemotherapy(CHOP)	died of progression of lymphoma	7
2000/[9]	67/M	SCC	MALToma/lung	lobectomy + chemotherapy (THP-COP)	died of pulmonary fibrosis due to chemotherapy	11
2001/[10]	74/M	Adenoca	MALToma/lung	lobectomy	alive	12
2002/[11]	67/M	SCC	MALToma/lung	lobectomy + chemotherapy (CHOP + carboplastin plus taxol)	alive	6
2008/[12]	73/M	Adenoca	MCL/pleura	chemotherapy Endoxan + Farmorubicin + Vincristine)	alive	14
2008/[13]	74/M	Adenoca	MALToma/lung	lobectomy, NHL was left untreated	N/A	N/A
2012/[14]	60/F	Adenoca	MALToma/lung	lobectomy, NHL was left untreated	N/A	N/A
2017/[15]	45/M	Adenoca	MCL/lung	6 cures of alternating RCHOP and RDHAP (dexamethasone, high-dose Ara-Cytarabine and cisplatin) + autologous stem cell transplantation.	died of treatment complications	36
2020/[16]	69/F	Adenoca	MALToma/lung	lobectomy + chemotherapy (CHOP)	alive	12
2020/[17]	64/M	SCC	MALToma/lung	N/A	N/A	N/A
2021/(The current case)	75/M	Adenoca	DLBCL/stomach	RFA + chemotherapy(R-CHOP) + Radioactive seed implantation	alive	27
2023/[18]	63/M	SCC	MALToma/lung	surgical resection	alive	N/A

SCC: squamous cell carcinoma; Adenoca: Adenocarcinoma; TCL: T-cell lymphoma; MALToma: Mucosa-associated lymphoid tissue lymphoma; MCL: Mantle cell lymphoma; DLBCL: diffuse large B-cell lymphoma; THP-COP: cyclophosphamide, pirarubicin, vincristine, and prednisolone

As presented in Table 1, all the twelve cases, including our case, were older than 45 years with a mean age of 66.8 years, and nine of them were men. All these cases suffered from non-small-cell lung cancer (NSCLC), and the most common type of lymphoma was mucosa-associated lymphoid tissue type (eight cases). The present case could be the first case of synchronous gastric lymphoma and lung cancer. Although the exact etiology of synchronous gastric lymphoma and lung cancer remains unknown, some scholars speculated that common predisposing factors, including smoking, Helicobacter pylori (H. pylori) infection, and genomic alternations, may play a role [9, 10, 13]. For the present case, however, the patient never smoked and was negative for H. pylori infection. In addition, the patient’s chromosome karyotype was normal, and no gene mutations other than EGFR were identified. Thus, whether the two primary malignancies observed in the present case were correlated or whether they were the result of independent events could not be confirmed.

Reviewing the eleven reported cases, the treatment protocols varied from observation to surgery, chemotherapy or in combination; however, the best treatment option remains controversial. Therefore, an individualized management is necessary. The present case is an old man who could not tolerate two entirely different types of chemotherapy, whereas R-CHOP regimen is the best choice for NHL; thus, the two lung cancer lesions were locally treated and managed first. CT-guided RFA was selected as it is an effective and minimally invasive treatment for medically inoperable NSCLC [19]. However, the left lung adenocarcinoma was not suitable for RFA; therefore, radioactive particle implantation was opted instead. Another key point to consider is prophylactic antifungal treatment before and during chemotherapy as the mortality of disseminated cryptococcosis after the R-CHOP regimen has been reported to be as high as 54% [20, 21]. After undergoing a series of treatment, the patient was finally discharged from our hospital with complete remission of gastric lymphoma and stable remission of lung adenocarcinoma; pulmonary cryptococcosis was also successfully treated.

In conclusion, synchronous primary diffuse large B-cell gastric lymphoma and bilateral primary lung adenocarcinoma is extremely rare, with the present case being the only one reported. This case highlights the need for proper staging and investigation of questionable findings before developing a patient’s treatment plan. The good clinical condition of the patient and CT scan results during the clinical follow-up indicated that the treatment was successful; however, the most suitable treatment protocol still needs to be identified on a case-by-case basis.

Abbreviations

CT

Computed tomography

HIV

Human immunodeficiency virus

NSCLC

Non-small-cell lung cancer

NHL

Non-Hodgkin’s lymphoma

DLBCL

Diffuse large B-cell lymphoma

GGO

Ground-glass opacity

RFA

Radiofrequency ablation

FDG

Fluorodeoxyglucose

PET-CT

Positron emission tomography-CT

SCC

Squamous cell carcinoma

TCL

T-cell lymphoma

MALToma

Mucosa-associated lymphoid tissue lymphoma

MCL

Mantle cell lymphoma

Author contributions

KLY and LW Conception or design of the study and drafting of the manuscript; KLY, KJ and JJW acquisition of the data; KLY, ZQY, KJ and LW critical revision of the manuscript for important intellectual content, LW final approval of the version to be submitted; All authors reviewed the manuscript.

Funding

This study was supported by Health Science and Technology Program of Shaoxing City (No. 2022KY070).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

The studies involving human participants were reviewed and approved by the ethics committee of the Affiliated Hospital of Shaoxing University. All methods were performed in accordance with the relevant guidelines and regulations. Informed consents were acquired from all study individuals for the acquisition of clinical and pathological information and the use of clinical specimens.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Competing interests

The authors declare no competing interests.