A Pancreatic Collision Tumor Comprising Mantle Cell Lymphoma and Adenocarcinoma: A Case Report and Literature Review

Abstract

A collision tumor is a rare clinical condition where two different tumors occur synchronically within a lesion. Pancreatic collision tumors with mantle cell lymphoma (MCL) are extremely rare and have only been reported in one case to date. We herein report an elderly patient with MCL and adenocarcinoma of the pancreas with Ann Arbor stage IV and Union for International Cancer Control stage IIB, respectively. The patient received palliative therapy and died 23 months after the diagnosis. Further research and case studies are required to investigate whether or not MCL-derived cyclin D1 overexpression affects the occurrence/growth of adenocarcinomas.

Introduction

Mantle cell lymphoma (MCL) is a type of B-cell lymphoma characterized by constitutive overexpression of cyclin D1. Chromosomal translocation (11;14)(q13;q32), which juxtaposes the BCL-1 gene with the immunoglobulin heavy chain (IGH) gene, is associated with the overexpression of cyclin D1. Cyclin D1 overexpression involves deregulating the G1/S cell cycle transition and promoting the malignant transformation of B cells (1). SOX11 also plays an essential role in oncogenesis and is known to be involved in blocking terminal B-cell differentiation and promoting tumor growth (1,2). High expression of SOX11 is observed in cyclin D1-positive and cyclin D1-negative MCL and in one-third of Burkitt's lymphoma cases (3).

Collision tumors are rare clinical conditions where two or more histologically distinct neoplasms occur synchronically within a neoplastic lesion. To our knowledge, only 16 cases of collision tumors comprising MCL and solid neoplasms have been reported. Furthermore, collision tumors of MCL and pancreatic cancer are extremely rare, with only a single such report published thus far (4).

We herein report an elderly patient with a collision tumor comprising MCL and adenocarcinoma in the pancreas who did not opt to undergo surgical resection. In addition, we conducted a literature review focusing on collision tumors comprising MCL and other neoplasms.

Case Report

An 82-year-old Japanese woman presented to the outpatient clinic with stomach discomfort and appetite loss for 1 week. The patient also noticed undigested stools but not watery diarrhea. She had no fever, nausea, weight loss, or night sweats. Her medical history included hypertension and appendectomy for appendicitis at 18 years old. A routine blood test performed two years before admission had shown no abnormalities in white blood cell counts, lactate dehydrogenase (LDH) levels, or hepatobiliary enzymes. The patient had no dementia, was independent in activities of daily living, and had no history of alcohol consumption or smoking. Family members living with the patient exhibited no symptoms.

A physical examination revealed mild tenderness in the upper right quadrant. Jaundice and leg edema were not observed. The lung sounds were clear, and the heart sounds were normal without murmurs. Laboratory test results were as follows: white blood cell count 38,300 /μL (lymphocyte 87%); hemoglobin 12.1 g/dL; platelet count 188,000 /μL; creatinine 0.61 mg/dL; total bilirubin 1.0 mg/dL; LDH 487 U/L (reference range, 125-245); aspartate aminotransferase 453 U/L (reference range, 10-40); alanine aminotransferase 512 U/L (reference range, 5-45); gamma-glutamyl transpeptidase 790 U/L (reference range, ＜48); and C-reactive protein 0.43 mg/dL (reference range, ＜0.3). No elevations in the tumor markers carcinoembryonic antigen or carbohydrate antigen 19-9 were found.

In a peripheral blood smear, medium-sized lymphoid cells with scant cytoplasm, irregular nuclei, and clumped chromatin were observed. Flow cytometry of the peripheral blood showed that the lymphoid cells were positive for CD5, CD19, and CD20 and negative for CD23, with kappa-type immunoglobulin light chain restriction. t(11;14)(q13;q32) was detected using fluorescence in situ hybridization (Fig. 1) and the expression frequency of the BCL-1/IGH fusion was 73.5% (reference range: ＜0.5%). The patient was diagnosed with MCL and classified as having a high risk of a poor prognosis according to the MCL International Prognostic Index (5).

Figure 1.

Peripheral blood fluorescence in situ hybridization testing. Peripheral blood fluorescence in situ hybridization testing shows BCL-1 (red dots) and immunoglobulin heavy chain (IGH) (green dots). The BCL-1/IGH fusion is indicated by yellow dots (arrows).

Contrast-enhanced computed tomography revealed slight swelling of the uncinate process of the pancreas (Fig. 2), enlarged lymph nodes in the pancreatic head and hepatic portal region, and splenomegaly. Diffusion-weighted enhanced magnetic resonance imaging showed an approximately 2-cm tumor in the pancreatic uncinate process and dilatation of the common and intrahepatic bile ducts. The patient underwent antibiotic therapy and endoscopic retrograde cholangiopancreatography with biliary stenting to treat cholangitis and was subsequently referred to a gastroenterologist for a definitive diagnosis of the pancreatic tumor.

Figure 2.

Contrast-enhanced computed tomography of the abdomen. The images show a lesion in the uncinate process of the pancreas (arrows) with poor arterial-phase enhancement (A) and strong venous-phase enhancement (B).

One month after the initial visit, the pancreatic tumor had increased to 3.1 cm in size and had invaded the bile ducts and duodenum without major blood vessel invasion. The patient underwent endoscopic ultrasound-guided fine-needle aspiration of the pancreatic tumor. Histopathology of the biopsy specimen showed that pancreatic adenocarcinoma coexisted with MCL cells. The MCL cells in the pancreas were positive for cyclin D1 and SOX11 expression (Fig. 3). Ki-67 expression was observed in 20% and 40% of MCL cells and adenocarcinoma of the pancreas specimen, respectively. The patient was diagnosed with pancreatic collision tumors comprising MCL and adenocarcinoma. The clinical stage of MCL was Ann Arbor stage IV, and that of pancreatic cancer was stage IIB according to the Union for International Cancer Control. After receiving information on treatment from both the gastroenterologist and hematologist, the patient opted for palliative care rather than surgical therapy because of her age and views on life.

Figure 3.

Histological findings of the pancreatic biopsy (20× magnification). (A) Small- to medium-sized lymphocyte aggregates in the pancreatic parenchyma. Lymphocytes are positive for CD20 and cyclin D1, which is a characteristic immunophenotype for mantle cell lymphoma. SOX11 expression was also observed. (B) Well-differentiated ductal adenocarcinoma (arrows) positive for cyclin D1 coexists with lymphoma cells.

Four months after the diagnosis, her peripheral blood lymphocyte counts exceeded 100,000 /μL. The patient began to have recurrent fevers, which quickly improved with 10 mg of oral prednisolone for a few days of each episode. After intermittent prednisolone administration, her lymphocyte counts decreased to less than 4,000 /μL, and splenomegaly also improved. In addition, 15 months after the diagnosis, the patient presented with abdominal distention and vomiting due to duodenal ileus, which improved by receiving 125 mg intravenous methylprednisolone (IVMP) once. One month later, the duodenal ileus recurred and improved with 125 mg IVMP therapy for 2 days. Esophagogastroduodenoscopy revealed no duodenal stenosis, but small gastric ulcers were noted. Histology of the gastric ulcer biopsy specimen revealed infiltration of MCL cells with positive immunostaining for cyclin D1 protein. The patient was discharged and continued to live at home with good oral intake and unassisted walking, although monthly IVMP was required because of duodenal ileus recurrence.

The patient's nutritional status gradually deteriorated due to repeated episodes of ileus, and parenteral nutrition through central venous access was initiated once a week. Twenty-one months after the diagnosis, the patient had IVMP-disabling ileus complicated with cholangitis. Endoscopic retrograde cholangiopancreatography showed that the duodenum and stent in the common bile duct were obstructed by pancreatic cancer. The patient died of advanced pancreatic cancer 23 months after the diagnosis (Fig. 4).

Figure 4.

The clinical course of the patient with a pancreatic collision tumor of mantle cell lymphoma and adenocarcinoma. The spleen index was calculated by multiplying the diameter (cm) of the major and minor axes of the spleen. A spleen index >40 cm² indicates splenomegaly. PSL: prednisolone, IVMP: intravenous methylprednisolone, MCL: mantle cell lymphoma, CBD: common bile duct, ENBD: endoscopic nasobiliary drainage, DS: duodenal stent, CVP: central venous port, WBC: white blood cell, LDH: lactate dehydrogenase, AST: aspartate aminotransferase, ALT: alanine aminotransferase, γ-GT: gamma-glutamyl transpeptidase

The patient provided her written informed consent for the publication of this report.

Discussion

To our knowledge, this is the second reported case of a pancreatic collision tumor where MCL and adenocarcinoma developed simultaneously. The patient's immediate cause of death was advanced pancreatic cancer. MCL did not progress rapidly, partly because frequent use of corticosteroids for symptom alleviation had modified the course of MCL.

Reports on MCL and solid collision neoplasms are presented in Table. In addition to pancreatic cancer (4), 15 cases of collision tumors of the MCL with cancers of the lung/pleura (6-10), gastrointestinal tract (11,12), liver (13), breast (14), penis (15), and prostate (16) as well as melanoma of the skin (17-20) have been reported. In most cases, MCL and solid neoplasms are detected synchronously, either within the neoplasm or in the metastatic lymph nodes. However, metachronous cases have occasionally been reported; MCLs preceded in two cases (4,17), and solid neoplasms preceded in two cases (13,15). Similar to our patient, 13% (2/15) of the reported cases were not accompanied by lymphadenopathy during the MCL diagnosis (11,16), 50% (3/6) were accompanied by splenomegaly (4,13,16), and 14% (1/7) were accompanied by lymphocytosis (18) during the MCL diagnosis. Regarding the treatment for collision MCL, nine cases received chemotherapy, four were observed without lymphoma chemotherapy, and three had no description. Of the nine patients for which a prognosis was described, two died of unidentified causes and septic shock associated with chemotherapy (Table).

Table.

Collision Tumors Comprising Mantle Cell Lymphoma and Solid Neoplasms

Case No. (reference No.)	Year reported	Age (years)	Sex	Collision lesions	Solid neoplasm with MCL			MCL presentation
					Primary site	Pathology	Synchronicity	Lymphadenopathy	Lymphocytosis*	Splenomegaly
1 (present case)	2023	82	Female	Primary site	Pancreas	Adenocarcinoma	Synchronous	-	+	+
2 (11)	1996	62	Male	Primary site	Esophagus	Squamous cell carcinoma	Synchronous	+	NR	NR
3 (17)	2002	64	Male	Lymph node	Scalp	Melanoma	Metachronous	+	NR	NR
4 (12)	2003	85	Male	Primary site	Colon	Adenocarcinoma	Synchronous	+	-	-
5 (6)	2004	58	Female	Lymph node	Lung	Small cell carcinoma	Synchronous	+	NR	NR
6 (7)	2008	73	Male	Primary site	Pleura/lung	Adenocarcinoma	Synchronous	-	NR	NR
7 (18)	2010	73	Male	Lymph node	Thigh	Melanoma	Synchronous	+	+	-
8 (4)	2013	65	Male	Metastatic site	Pancreas	Adenocarcinoma	Metachronous	+	-	+
9 (16)	2014	74	Male	Primary site	Prostate	Adenocarcinoma	Synchronous	-	-	+
10 (14)	2017	65	Male	Lymph node	Breast	Adenocarcinoma	Synchronous	+	-	-
11 (15)	2017	85	Male	Lymph node	Penis	Squamous cell carcinoma	Metachronous	+	NR	NR
12 (8)	2018	55	Female	Primary site	Lung	Adenocarcinoma	Synchronous	+	NR	NR
13 (9)	2018	61	Male	Lymph node	Lung	Adenocarcinoma	Synchronous	+	NR	NR
14 (10)	2018	71	Male	Pleural effusion	Lung	Adenocarcinoma	Synchronous	+	-	NR
15 (19)	2019	61	Male	Primary site	Neck	Melanoma	Synchronous	+	NR	NR
16 (20)	2020	60	Female	Primary site	Neck	Melanoma	Synchronous	NR	NR	NR
17 (13)	2022	46	Male	Primary site	Liver	Hepatocellular carcinoma	Metachronous	+	-	+
Case No. (reference No.)	Initial therapy for collision tumors				Observation period since MCL diagnosis (month)		The final status of the observation period
	MCL		The other tumor
1 (present case)	Corticosteroid**		No specific therapy		23		Died of pancreatic cancer
2 (11)	CEOP		Surgical resection		NR		NR
3 (17)	No specific therapy		Surgical resection		NR		NR
4 (12)	NR		Surgical resection		<1		Died of unidentified cause
5 (6)	Rituximab		Cisplatin and etoposide		30		Both tumors are in relapse
6 (7)	CEO		Surgical resection		14		Both tumors are in CR
7 (18)	No specific therapy		Surgical resection		NR		NR
8 (4)	Rituximab		FOLFOLINOX		12		Both tumors are in SD
9 (16)	BR		NR		NR		NR
10 (14)	CHOP		Surgical and endocrine therapy		54		Both tumors are in CR
11 (15)	NR		NR		NR		NR
12 (8)	No specific therapy		Surgical resection		12		MCL is in PD; and then lost follow-up
13 (9)	NR		NR		NR		NR
14 (10)	CHOP, followed by BR		No specific therapy		3		Died of septic shock
15 (19)	Rituximab-hyper CVAD		Surgical resection		NR		NR
16 (20)	No specific therapy		Immunotherapy		6		MCL is in SD
17 (13)	Rituximab-CHOP		TACE		5		MCL is in CR; HCC in PR

BR: bendamustine and rituximab, CEO(P): cyclophosphamide, epirubicin, vincristine, (and prednisolone), CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisolone, CR: complete remission, FOLFOLINOX: oxaliplatin: irinotecan: fluorouracil, and leucovorin, Hyper CVAD: cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine, MCL: mantle cell lymphoma, NR: not reported, PD: progressive disease, PR: partial remission, SD: stable disease, TACE: transcatheter arterial chemoembolization

^*Lymphocytosis was defined by an increase in lymphocyte counts ≥4.0×10³/µL

^**For alleviating symptoms

Cyclin D1 regulates gene transcription and the cell cycle (1) and may contribute to oncogenesis, not only in MCL but also in other neoplasms, including adenocarcinoma of the pancreas (21), esophagus (22), and lung (23) as well as cutaneous melanoma (24). For pancreatic cancer, cyclin D1 is reported to be involved in cancer cell proliferation and vascular invasion, and its overproduction is associated with a poor prognosis (21). Suppression of cyclin D1 has also been shown to reduce the development and growth of pancreatic cancer cells in vitro (25). In addition, tumor-infiltrating B cells may be associated with the development and progression of pancreatic adenocarcinoma through multiple mechanisms, including the suppression of immune cells to attack cancer in the tumor microenvironment (26). As whether or not MCL-derived cyclin D1 overexpression influences the occurrence or growth of other tumors remains unclear at present, further research and case studies are needed.

Even when MCL is demonstrated in the peripheral blood, bone marrow, or lymph nodes, other solid neoplasms may be present synchronously in extranodal lesions. Therefore, a careful evaluation of extranodal lesions is necessary in patients with MCL.

The authors obtained written informed consent for the publication of these findings from the patient.

The authors state that they have no Conflict of Interest (COI).