Pancreatic hamartoma: A rare and benign cause of pancreatic incidentaloma

Pancreatic hamartomas (PH) represent less than 1% of all hamartomas. They are composed of disorganized acinar, islet, and ductal cells^1,2. Given their low incidence, it is difficult to differentiate them from other low-grade benign or malignant tumors, requiring pathological and immunohistochemical studies of the surgical specimen for definitive diagnosis². We present the first case of PH described in Spain.

A 41-year-old male patient was evaluated at our hospital for an incidental finding of abdominal magnetic resonance imaging (MRI) of a 17 × 12 × 15 mm pancreatic mass. Blood levels of amylase, bilirubin, carcinoembryonic antigen, Ca 19-9, gastrin, and neuron-specific enolase were normal, as were 5-hydroxyindoleacetic acid levels.

After 10 months of follow-up, the abdominal MRI revealed a lesion in the pancreatic body measuring 20 × 18 × 17 mm that was hyperintense on T2, suggestive of a cystic component vs central necrosis, and slightly hypointense in the periphery with progressive enhancement in the portal and late phase (Fig. 1). Given the presence of a solid component, malignancy could not be ruled out. We suspected a neuroendocrine tumor and requested an octreotide scan, which was normal.

Fig. 1.

Magnetic resonance showing a 20-mm lesion, well defined and hyperintense in T2, in the body of the pancreas (white arrow) and its relationship with the pancreatic duct.

Endoscopic ultrasound revealed a 19 mm lesion in the body of the pancreas that was hypoechogenic, well defined and solid with a central cystic area. Fine-needle aspiration biopsy showed a columnar epithelium with mucinous cells and no atypia. The patient was initially diagnosed with a mucinous tumor (not intraductal mucinous papillary tumor), ruling out solid pseudopapillary tumor (SPT) or a neuroendocrine tumor.

Given the patient’s age, the limited growth of the lesion and the inability to clarify its nature, we performed open spleen-preserving distal pancreatectomy (DP). Macroscopically, the mass was firm and whitish, measuring 1.8 × 1.8 cm. Microscopically, it consisted of randomly distributed ductal, acinar, and neuroendocrine structures embedded in a fibrocellular stroma, with no significant inflammatory infiltrates. Immunohistochemically, the stroma was positive for ß-catenin; negative for IgG, IgG4, synaptophysin, chromogranin, actin, CD34, S100, and Bcl2. In the end, the patient was diagnosed with PH.

The patient developed a type A pancreatic fistula, which was treated conservatively, and he was discharged on the 7th postoperative day with a pancreatic drainage tube, which was removed on the 10th postoperative day. After 5 months of follow-up, he has not presented recurrence of the disease.

PH are extremely rare. Described for the first time in 1977 by Anthony et al.³, 43 cases have been published since, including the present one (Table 1). They can appear at any age, although the average age is 40–60 years. There is no tendency for PH to affect either sex. Most are either diagnosed incidentally or present with nonspecific signs and symptoms, such as abdominal pain or weight loss. Only one case has been reported that began with obstructive jaundice⁴. PH can appear anywhere in the pancreas, although most frequently in the head, with a size of 1.0–14.0 cm⁵.

Table 1.

Clinical-pathological characteristics of pancreatic hamartomas described in the literature (n = 43).

Author	Age	Sex	Symptoms	Location	Size (cm)	Dilatation of the pancreatic duct	Preoperative diagnosis	Image	Surgery	Pathological type	Follow-up (months/results
Anthony et al.^3 (1977)	46	M	Asymptomatic	Head	1.6	NR	NR	NR	PD	S/C	NR/NR
Anthony et al.^3 (1977)	35	M	Epigastric pain	Tail	Multiple	–	NR	NR	LR	NR	NR/NR
Anthony et al.^3 (1977)	58	M	Asymptomatic	Head	1	NR	NR	NR	Autopsy	NR	NR/Exitus
Burt et al.^11 (1983)	0	F	Hypoglycemia and hypercalcemia	Diffuse	11.5	–	NR	S	Total pancreatectomy	S	3/Exitus
Flaherty and Benjamin^12 (1992)	20 meses	F	Abdominal distension	Head	9	NR	NR	S/C	LR	S/C	9/alive
Izbicki et al.^13 (1994)	25	M	Epigastric pain	Head	10.6	NR	NR	S/C	PD	S/C	48/alive
Wu et al^14 (1998)	39	M	Abdominal pain and weight loss	Head	8	NR	NR	NR	PD	NR	9/alive
McFaul et al.^15 (2004)	29	M	Abdominal pain and weight loss	Head	1	–	NET	NR	PD-PP	NR	24/alive
McFaul et al.^15 (2004)	62	M	Abdominal pain and weight loss	Head	3.5	–	NR	NR	PD	NR	3/alive
Pauser et al.^16 (2005)	36	F	Epigastric pain	Head	7	–	NR	S/C	PD	S/C	15/NR
Pauser et al.^16 (2005)	55	F	Abdominal pain	Neck	3	–	NR	S/C	DP + splenectomy	S/C	23/alive
Pauser et al.^17 (2005)	51	M	Asymptomatic	Tail	3	–	Tumor of unknown origin	NR	LR	S	24/alive
Pauser et al.^17 (2005)	54	F	Abdominal pain	Body	2	–	NR	NR	DP	S	48/alive
Nagata et al.^1 (2007)	58	F	Asymptomatic	Body	2	–	NET	NR	DP	S	6/alive
Thrall et al.^18 (2008)	3	M	Abdominal pain	Head	3	NR	NR	S/C	PD	S/C	NR/NR
Sampelean et al.^19 (2009)	46	M	Abdominal mass	Head	8	NR	NR	NR	PD	S	NR/NR
Durczynski et al.^8 (2010)	69	M	Asymptomatic	Body	3	–	NR	NR	CP	S	55/alive
Kim et al.^2 (2012)	52	F	Abdominal pain	Head	2.2	–	SPT or cystic serous neoplasm	S/C	PD-PP	S/C	10/alive
Kawakami et al.^20 (2012)	78	F	Asymptomatic	Head	Multiple	–	Pancreatic carcinoma	S	DP	S	30/alive
Sueyoshi et al.^21 (2013)	14 meses	M	Abdominal distension	Tail	14	–	Pseudo-cystic blastoma	S/C	LR	S/C	26/alive
Yamaguchi et al.^6 (2013)	78	F	Asymptomatic	Head	1.7	NR	Pancreatic carcinoma	NR	NR	S	32/alive
Yamaguchi et al.^6 (2013)	61	F	Abdominal pain	Head	4	NR	SPT	NR	NR	S	7/alive
Yamaguchi et al.^6 (2013)	71	F	Asymptomatic	Body	5	NR	Cystic tumor	NR	NR	S/C	68/alive
Yamaguchi et al.^6 (2013)	59	F	Abdominal pain	Tail	1	NR	NET	NR	NR	S	10/alive
Yamaguchi et al.^6 (2013)	53	M	Abdominal pain	Head	8	NR	SPT	NR	NR	S/C	9/alive
Yamaguchi et al.^6 (2013)	53	M	Asymptomatic	Head	2.5	NR	Mass-forming pancreatitis	NR	NR	S/C	12/alive
Inoue et al.^4 (2014)	65	M	Obstructive jaundice	Head	4	+	NR	S	PD	S	36/alive
Addeo et al.^22 (2014)	61	F	Asymptomatic	Body	2.6	+	NR	S	Robotic DP + splenectomy	S	NR/NR
Shahbaz et al.^23 (2015)	62	F	Epigastric pain	Head	1.4	–	Pancreatic carcinoma	NR	PD	NR	NR/NR
Zhang et al. (2016)^7	53	F	Abdominal pain and weight loss	Head	2.3	–	Tumor of unknown origin	NR	PD	S	55/alive
Nagano et al.^24 (2017)	72	F	Asymptomatic	Head	2	+	NR	NR	PD-PP subtotal	S	36/alive
Delgado et al.^25 (2017)	0	F	Asymptomatic	NR	1.2	–		NR	Autopsy	S/C	NR/Exitus
Han et al^9 (2018)	35	F	Hypoglycemia	Tail	1	–	NET	S	DP	S/C	NR/NR
Tanaka et al.^26 (2018)	54	M	Asymptomatic	Body	3.6	NR	IPMN, malignant lipomatous tumor	S	DP	S lipomatous	NR/NR
Tanaka et al.^26 (2018)	74	M	Asymptomatic	Head	5	NR	Lipoma	S	PD	S lipomatous	NR/NR
Tanaka et al.^26 (2018)	67	M	Asymptomatic	Tail	6.5	NR	Liposarcoma	NR	DP	S/C lipomatous	NR/NR
Shin et al.^27 (2019)	54	F	Asymptomatic	Head	2.2	–	SPT or NET	NR	Robotic PD-PP	S	6/alive
Nahm et al.^28 (2019)	42	F	Abdominal pain	Neck	2.8	–	SPT	S/C	CP	S/C	8/alive
Hosfield et al.^29 (2019)	4	M	Abdominal pain, steatorrhea	Head	9.5	NR	SPT, pancreatoblastoma, IPMN	S/C	PD	S/C	1/alive
Cui et al.^5 (2020) ()	57	F	Asymptomatic	Head	3	–	NET	S/C	PD	S/C	34/alive
Cui et al.^5 (2020)	69	M	Asymptomatic	Head	1.5	–	Tumor of unknown origin	S	PD	S	44/alive
Toyama et al.^10 (2020)	53	M	Asymptomatic	Head	3.7	–	NET, IPMN, SPT hemangioma	S/C	PD	S/C	NR/NR
Caso actual (2020)	41	M	Asymptomatic	Body	1.8	–	Mucinous tumor	S/C	DP	S/C	5/alive

PD: pancreaticoduodenectomy; PD-PP: PD with preservation of the pylorus; F: female; M: male; NR: no reported; CP: central pancreatectomy; DP: distal pancreatectomy; LR: local resection; S: solid; S/C: solid and cystic; NET: neuroendocrine tumor; IPMN: intraductal papillary mucinous neoplasms; SPT: solid pseudopapillary tumour.

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Two types of PH are distinguished according to the macroscopic findings: solid type and solid-cystic type⁶. On ultrasound, they appear to be hypoechoic masses with well-defined margins^4,5,7,8.

On computed tomography scans, PH are usually well defined, with a slightly unequal density in solid lesions, hypo- or isodense, with progressive heterogeneous enhancement in late phases. The margins are typically well defined after contrast enhancement^1,2,5,9. Contrarily, pancreatic adenocarcinomas are characterized by low enhancement and the invasion of adjacent structures, while NET show clear enhancement in the initial phases after contrast^5,9. SPT are similar but usually present encapsulation and peripheral calcifications¹⁰. Therefore, PH should be included in the differential diagnosis of pancreatic incidentalomas.

On MRI, the contour is regular, with well-defined edges in T2. The intensity of the interior of the lesion is slightly heterogeneous, hypointense on T1 and iso- or hyperintense on T2^5,7,9.

Microscopically, PH are composed of a variable proportion of acinar, ductal, and endocrine cells arranged in a disorganized manner, so fine-needle aspiration is not effective. The solid component consists of fibroadipose tissue, while the cystic component is made up of dilated pancreatic ducts. They present differentiated acinar cells, without forming well-organized lobules^1,6,7, and characteristically lack 3 structures: concentric elastic fibers around the pancreatic ducts, peripheral nerves, and well-formed Langerhans islets. This distinguishes PH from chronic pancreatitis and hamartoma of the pancreatic duct, where these 3 structures are well preserved⁶.

Although PH is a benign disease, most patients undergo surgical resection because it is impossible to rule out malignant disease. Given the higher frequency of malignancy or premalignancy in pancreatic incidentalomas, surgery is the indicated treatment, be it pancreaticoduodenectomy, DP, or conservative surgery (central pancreatectomy or enucleation), even though this may be too aggressive in the case of benign tumors⁸.

Some authors suggest that conservative surgery should be performed to preserve the integrity of the gastrointestinal tract and the endocrine and exocrine function of the pancreas and spleen due to the indolent nature of this tumor⁷. We opted for spleen-preserving DP due to the initial suspicion, and we decided against performing parenchyma-sparing surgery due to the risk of fistula, given the proximity of the tumor to the main pancreatic duct (Fig. 1).