Primary colorectal diffuse large B-cell lymphoma initially presenting with pleural effusion: report of one case and review of literature

Abstract

Gastrointestinal (GI) diffuse large B-cell lymphoma (DLBCL) is one of the frequently reported histologic subtypes of non-Hodgkin lymphoma (NHL) that occur in the GI tract. However, the presentation of quite different clinical manifestations, morphologic characteristics, immunophenotypes, and molecular biologic features is challenging for its diagnosis. Herein, we describe a rare case of primary colorectal DLBCL that occurred in a 59-year-old immunocompetent Chinese female who attended our respiratory clinic for the third time with an asymptomatic pleural effusion and pleural thickening. In her clinical setting, there was no history of trauma or travel, and no evidence of infections, connective tissue diseases, or malignancies such as pleural mesothelioma. Lymphoma was highly suspected for the enlargement of systemic lymph nodes and the multiple polypoid appearance in the rectum found by endoscopy examination. In a repeated colonoscopy, immunohistochemical and molecular features of the multiple “polyps” allowed diagnosis of colorectal diffuse large B-cell NHL. To our knowledge, this is the first case of a verified diagnosis of pleural effusion associated with a primary colorectal DLBCL. The purpose of this report is to alert clinicians that when we evaluate the causes of unexplained pleural effusion, lymphoma should be considered, particularly when the available examination data cannot be corroborated by clinical manifestations.

Introduction

Diffuse large B-cell lymphoma (DLBCL), first reported by Harris, is one of the most prominent histologic subtypes of malignant lymphoma and represents up to 30% of non-Hodgkin lymphoma (NHL) cases [1]. Studies show that gastrointestinal (GI) lymphoma accounts for 40% of extranodal DLBCL, and the lymphoma involvement in the GI tract leads to a variety of lesions and nonspecific symptoms that render the diagnosis particularly challenging [2]. Herein, we describe a rare case of rectal DLBCL that occurred in a 59-year-old immunocompetent Chinese female who had a 2-year history of unexplained pleural effusion and pleural thickening. To our knowledge, this is an unusual report of uniateral pleural effusion associated with primary rectal DLBCL.

A case report

A 59-year-old immunocompetent woman had a medical history of 20 years of large artery stenosis, seven years of controlled hypertension, and no history of smoking or alcohol consumption. She attended our respiratory clinic on July 25, 2018, for the third time in two years, with the primary clinical manifestation of unilateral pleural effusion. She denied having had fever, cough, rash, joint pain, or chronic diarrhea, and there was no history of trauma, travel, or surgery, and no family history of malignancy or connective tissue disease (CTD). Blood, urine, stool tests, as well as biochemical, coagulation, and thyroid function tests were within normal limits. The tumor biomarkers were almost normal, except for a slight increase of CA125 to 245.2 U/mL (Normal range: 0.0-22.0 U/mL). Infections were also ruled out, including tuberculosis and human immunodeficiency virus (HIV), and CTD was also not considered. A computed tomography (CT) scan of the chest revealed multiple high-density shadows, enlarged lymph nodes in the mediastinum, and both a massive pleural effusion in the left thoracic cavity and small pleural nodular lesions thickening the pleura (Figure 1). Considering that the patient had never had thoracic surgery or experienced trauma, malignancy was suspected. However, subsequent bronchoscopy and thoracoscopy examinations demonstrated only mild chronic inflammation without any evidence of infection or malignancy (Figures 2 and 3). GI endoscopy was then carried out, and finally her second colonoscopy verified the diagnosis of left-sided pleural effusion associated with a rectal DLBCL (Figure 4). The symptoms and the pleural effusion disappeared after a traditional Chinese medicine treatment was administered.

Figure 1.

Chest CT revealed multiple high-density shadows, mediastinal lymph node metastatic nodules, and a left pleural effusion.

Figure 2.

Autofluorescence bronchoscopy and histopathologic findings. The autofluorescence bronchoscopy revealed smooth bronchial mucosa and an unobstructed bronchial lumen. Histopathologic characteristics included chronic inflammation of the mucosa.

Figure 3.

Thoracoscopic and histopathologic findings. The fibrous tissue of “parietal pleura” hyperplasia was accompanied by lymphoid tissue hyperplasia and mesodermal tissue hyperplasia.

Figure 4.

(A, B) Colonoscopic and histopathologic manifestations. Histopathologic and immunohistochemical studies of the rectal excision specimens demonstrated CD19 (+), CD20 (+), CD79a (+), CD30 (+), Bcl-2 (partial +), Bcl-6 (+), κ (partial +), CD10 (+), PAX-5 (+), CD38 (partial +), and Ki-67 (50%+). This was consistent with diffuse large B-cell lymphoma (DLBCL) cells. Original images are ×50 magnification. (C) Representative micrographs of immunohistochemical staining for Ki-67, (D) CD3, and (E) CD20. Original images of (C, D) are ×200 magnification, and (E) are ×100 magnification.

Discussion

The GI tract is a common site for the presentation of extranodal lymphomas, with increasing incidence worldwide [1-3]. However, the primary colorectal lymphoma is quite rare, constituting only 0.2% of all colorectal malignancies. GI lymphomas can be difficult to diagnose, particularly in small samples, when early in development, or when unusual types are involved [1,4,5].

According to the existing literature, the clinical characteristics of GI DLBCL are always variable. In addition to the most commonly encountered GI symptoms of nausea, vomiting, dyspepsia, abdominal pain, mass or anemia, hypoproteinemia, and weight loss, GI DLBCL involves posterior peritoneum lymph nodes, the uterus, and pancreas; and it may present as a skin lesion, upper GI bleeding, ulcerative colitis, acute pancreatitis, ascites, or intestinal obstruction due to invasion into different organs [6,7]. It occurs in a location-based manner. In a setting of colorectal DLBCL, abdominal pain, bowel obstruction, a palpable mass, and rectal bleeding occur most frequently [6-8]. However, isolated colorectal involvement and intestinal perforations are very rare, and only a few cases have been reported. Table 1 summarizes some of the unusual manifestations of colorectal DLBCL: an 82-year-old female with acute chest pain, and others having acute pancreatitis or night sweats, fever, and cough. Certainly, it should be noted that some of the clinical features or those revealed by endoscopic investigation may be caused by metastatic GI lymphoma infiltration. As stated earlier, one-sided pleural effusion or pleural thickening is not commonly seen in either GI DLBCL or in patients with primary or metastatic rectal DLBCL. Only a few cases of peritoneal and omental infiltration have been reported in patients with GI DLBCL associated with ascites and pleural effusion [9]. Lymphomas can occur at any site of the body, but the diffuse and extensive involvement of the peritoneal cavity is unusual and rare. In fact, pleural thickening and enlarged lymph nodes may be more detected in the clinical practice of malignant mesothelioma, chronic pleural inflammation, or sarcoidosis. In the present case, the patient initially had unilateral pleural effusion, and this symptom had recurred three times. In particular, the pleural effusion could be absorbed without any treatment. It was a quite inert manifestation that rarely happens in malignant mesothelioma, chronic pleural inflammation, or sarcoidosis, reducing the suspicion of malignancy or malignant metastasis for clinicians. This study surmised that the reason for the pleural effusion in the patient was a tumor metastasis causing lymphatic obstruction.

Table 1.

Review of cases of rare manifestations of GI diffuse large B-cell lymphoma (DLBCL)

Authors	Patient information	Clinical features or endoscopic investigation	Diagnosis
Papakonstantinou IP et al. [9]	A 66-year-old woman with low complement levels, resembling systemic lupus erythematosus	Persistent afebrile abdominal pain and bloody diarrhea	Primary colon DLBCL
Telci CO et al. [10]	A 77-year-old male with no risk factors	Hemorrhagic shock due to the massive hematemesis and hematochezia; GI endoscopy revealing a mosaic pattern and multiple ulcers	Primary gastric DLBCL
Tahir M et al. [11]	A 47-year-old male with no risk factors	Worsening RLQ abdominal pain, decreased appetite, and weight loss; imaging revealed cecal mass with distended bowel, and colonoscopy revealed a large mass obstructing the whole lumen of the cecum	Primary colon DLBCL
Jo HH et al. [12]	An 82-year-old female with no risk factors	Acute onset chest pain and vomiting; abdominal CT revealed a gastrogastric intussusception	Primary gastric DLBCL
Quera R et al. [13]	A 47-year-old male	Ulcerative colitis	Primary rectal DLBCL
Ohkura Y et al. [14]	A 53-year-old man	Spontaneous gastric perforation; a giant ulcer with the necrotic matter on the ulcer floor was seen on upper GI endoscopy	Primary gastric DLBCL
Genovese F et al. [15]	An 83-year-old Caucasian man	Intermittent anal bleeding and irregular bowel	Primary DLBCL developing within a rectal tubular adenoma with low-grade dysplasia
Santharam V et al. [16]		Sudden-onset abdominal pain with features of shock and peritonitis; jejunal perforation with abnormal lymph nodes	Primary jejunal DLBCL
Xu XQ et al. [17]	An 82-year-old man	Intermittent abdominal pain, nausea, and fatigue; CT scan of the abdomen revealed a mass in the terminal ileum with a sign of “bowel within bowel”, which was suspicious for ileo-ileum intussusception	Primary ileum DLBCL
Tanaka S et al. [18]	A 38-year-old homosexual man diagnosed with human immunodeficiency virus infection	Anemia; GI endoscopy revealed multiple dish-like lesions, ulcerations, bloody spots, nodular masses with active bleeding in the stomach, erythematous flat lesions in the duodenum, and multiple nodular masses in the colon and rectum	AIDS-related GI DLBCL
Barbaryan A et al. [19]	An 84-year-old Caucasian female	Altered mental status, acute kidney injury, and hypercalcemia; colonoscopy showed a large ulcerated mass	Primary colorectal lymphoma
Yamada R et al. [20]	A 49-year-old man	Acute pancreatitis; upper GI endoscopy showed an all-round ulcerative lesion from the superior duodenal angle to the descending portion	Primary GI duodenal malignant lymphoma
Barut F et al. [21]	A 25-year-old male patient	Multifocal and skip involvement imitating Crohn’s disease and attracting attention with a cobblestone-like appearance	Primary intestinal DLBCL forming multiple lymphomatous polyposis

Although a clear diagnosis was finally made, it took a long time. If an FDG-Positron Emission Tomography/Computed Tomography (PET/CT) scan had been performed, an early diagnosis could have been made. At diagnosis, the total-body FDG-PET/CT scan can identify areas of lymphoma missed by CT alone and avoid the undertreatment of patients with advanced disease stage who have been misclassified based on CT as suffering from limited-stage disease [22]. Particularly in Hodgkin lymphoma, the FDG-PET/CT scan offers a significant incremental benefit in the diagnosis and staging assessment, and a potential improvement in treatment strategies [23]. However, a whole-body scanning with PET/CT cannot be successfully carried out in resource-limited settings or rural areas of the country due to the cost and technical requirements. Notably, the patient in this study refused to undergo FDG-PET/CT scanning because of the huge cost.

Histopathology is the gold standard for the diagnosis. However, GI lymphomas usually pose difficulties in diagnosis, particularly in small samples, when early in development, or when of an unusual type. The reasons are essentially twofold: (1) the small size of biopsies, limiting the extensive evaluation usually performed on comparable lymph node samples, and (2) confusion of lymphoma with benign and reactive lymphoid proliferations in the GI tract [24,25]. In the present study, the patient accepted colonoscopy twice, plus thoracoscopy and bronchoscopy. It may not be an individual phenomenon. Fortunately, the multiple polypoid appearance in the rectum raised the suspicion of GI lymphoid infiltration. O’Malley et al. [26] have already pointed out the need for additional evaluation for prominent GI intraepithelial infiltrates of small lymphocytes or lymphoepithelial lesions, dense infiltrates of large lymphoid cells, and multiple “polyps” containing dense lymphoid infiltrates. These data supported the initial hypothesis that a lymphoproliferative disease was involved in this case. The current report will improve the accuracy of diagnoses that take into consideration clinically or pathologically defined background settings defined in the literature.

Conclusion

A rare case of primary colorectal lymphoma initially presented with pleural effusion. Lymphoma involvement in the GI tract presents with a variety of lesions, and the nonspecific symptoms make the diagnosis challenging. A repeated pleural effusion is not just for a sign of infection, CTD or pleural mesothelioma. In certain clinical settings, malignancies, particularly nonsolid malignancies, should be considered. Despite its low probability, GI DLBCL with mediastinal lymph node metastasis may result in unexplained, repeated pleural effusion. Accordingly, the noninvasive imaging technique of PET/CT or at least a comprehensive CT scan or endoscopic examination is recommended in such conditions.

Disclosure of conflict of interest

None.

Abbreviations

DLBCL

Diffuse large B-cell lymphoma

NHL

non-Hodgkin lymphoma

GI

gastrointestinal

CTD

connective tissue disease

HIV

human immunodeficiency virus

CT

computed tomography

PET/CT

Positron Emission Tomography/Computed Tomography