Keywords chylous ascites - pancreatic neoplasms - lymph node - plasmacytoid
Chylous ascites, also known as chyloperitoneum or lymphorrhagia, is a rare lesion
of adults, with a reported incidence of 1:20,500, which is defined by the presence
of a milky and lipid-rich fluid in the peritoneal cavity.[1 ]
[2 ]
[3 ]
[4 ]
[5 ]
[6 ]
Lymphatic fluid is characterized by thick consistency, cell count >500/mL, with lymphocytic
predominance, total protein level between 2.5 and 7.0 g/dL, with serum to ascites
albumin gradient (SAAG) less than 1.1 g/dL, lactate dehydrogenase (LDH) between 110
and 200 IU/L, glucose level >100 mg/dL, and triglyceride level in ascetic fluid >110 mg/dL.[1 ]
[2 ]
In this paper, we present an unusual case of a ductal carcinoma of the pancreatic
tail (PDAC) associated with chylous ascites, as result of tumor emboli-related blockage
of the lymphatic flow. A review of literature was also done.
Case Report
A 76-year-old male was admitted to the general surgery department with 1-month history
of abdominal pain, weight loss (5 kg in the last month), accusing nausea, and multiple
episodes of emesis. He was a social drinker and he quitted smoking 2 years ago. He
also related to be treated for arterial hypertension.
At the present admission, the tenderness painful abdomen was diagnosed as acute abdomen.
The ultrasound examination showed pancreatic enlargement and suspicion of a pancreatic
cancer was done. The computed tomography (CT scan) with contrasting substance revealed
that a pancreatic nodular mass, larger than 50 mm which infiltrate the pancreatic
body and tail, was extended in the splenic hilum and associated multiple supra- and
subdiaphragmatic adenopathy.
Bilateral deep vein thrombosis of the femoral and popliteal veins were associated
and interpreted as Trousseau's sign. Emergent laparotomy was decided.
The signed informed consent for surgical intervention and publication of data was
obtained before surgery.
The exploratory laparotomy revealed an infiltrative tumor mass of the mild portion
of the pancreas, penetrating the celiac trunk, inferior mesenteric vein, and spleno-portal
confluent, with peripancreatic adenopathy. A moderate quantity of whitish and milky-like
fluid was identified in the peritoneal cavity and was collected for biochemistry examination.
Subtotal spleno-pancreatectomy was performed, with the suture of celiac trunk, inferior
mesenteric, and portal vein. The surgical specimens were sent for histopathological
examination.
Laboratory examination of the peritoneal fluid revealed 295 mg/dL triglycerides, more
than 500 cells/mL, with the majority of them being lymphocytes, a protein count of
5.4 g/dL, with SAAG of 0.94 and LDH of 187 IU/dL. The glucose level of the abdominal
fluid was not quantified. With five out of six diagnostic criteria achieved, the diagnosis
of chylous fluid was established.
Macroscopic examination of the surgical specimens revealed a 50 × 40 × 40-mm white
and infiltrative mass involving the middle and distal portion of the pancreas, with
direct infiltration of the spleen hilum, free pancreatic lateral and posterior margin
and crossing of the pancreatic anterior margin. Multiple tumor deposits were also
identified in the peripancreatic tissue.
Microscopically, the well-defined tubular structures, some of them being hugely dilated,
alternated with poorly differentiated areas ([Fig. 1 ]). The tumor cells proved positive for carcinoembryonic antigen and maspin, and negative
for chromogranin, synaptophysin, and neuroendocrine cluster of differentiation (CD56)
and S100. Invasion of over 10 of the peripancreatic and spleen hilum lymph nodes conglomerates
associates perineural invasion and presence of tumor emboli in over 20 of the significantly
enlarged lymph vessels. In the metastatic tissue and emboli, the tumor cells were
dyscohesive and showed high pleomorphism ([Fig. 2 ]). The metastatic discohesive cells showed plasmacytoid morphology, with eccentrically
located nuclei, indistinct nucleoli, and eosinophilic cytoplasm.[7 ]
Fig. 1 The histologic examination of the pancreatic ductal adenocarcinoma reveals in hematoxylin
eosin, tubular structures located in a poorly defined stroma.
Fig. 2 Lymphangiosis carcinomatosa is defined by the presence of multiple tumor emboli within
the dilated lymph vessels (A, B ). Examination of the metastatic lymph nodes reveals poorly defined tubular structures
and highly pleomorphic dyscohesive tumor cells with plasmacytoid morphology (C ).
The microscopic features, correlated with the immunoprofile of the tumor cells and
clnicopathological characteristics, allowed the diagnosis of a pathologic tumor-node
stage III (pT4N2) poorly differentiated PDAC with lymhangiosis carcinomatosa (carcinomatosis
of lymph vessels) and chyloperitoneum.
The postoperative evolution was unfavorable, the chylous ascites was persistent, despite
persistent drainage, and patient died at 3 weeks after surgery.
Discussion
In children, congenital abnormalities and traumatic disruption of the lymph vessels
are the commonest causes of chylous ascites. In adults, this is an extremely rare
lesion, which can be related on tumor and nontumor lesions ([Table 1 ]).
Table 1
Etiology and mechanisms of occurrence of chylous ascites
Etiology
Mechanism
Acquired
Mechanic, traumatic agents
Obstruction or disruption of main lymph vessels
Surgical technique imperfections
Infectious agents with lymph vessels tropism (tuberculosis, filariasis)
Autoimmune diseases (systemic lupus erythematous)
Cirrhosis
Lymph overflow
Cardiac diseases
Tumors (lymphomas, pancreatic ductal adenocarcinoma, gastrointestinal neuroendocrine
tumors/adenocarcinomas, sarcomas)
Fibrosis of lymph vessels and/or lymph nodes
Radiotherapy
Congenital
Lymphangiectasia
Congenital malformations
Lymphangioma
Congenital syndromes (such as Klippel-Trenaunay syndrome)
In developed, western countries, abdominal tumors, cirrhosis, and iatrogenic lymph
vessels disruption during surgery accounts for more than half of chylous ascites,
while in developing countries, the most frequent etiologies responsible for this condition
are infectious diseases like tuberculosis and filariasis.[1 ]
[2 ]
The main mechanisms of acquired chylous ascites are the following ones: traumatic
disruption of thoracic duct, obstruction of lymphatic flow, caused by infectious agents
or tumor cells, fibrosis of the lymph vessels wall, in patients with autoimmune diseases
or after radiotherapy, or increased lymph fluid production, such in cirrhosis or cardiovascular
diseases.[3 ]
[6 ]
[8 ]
[9 ]
[10 ]
Although rare, malignancies such as lymphomas (30% of all reported cases), Kaposi
sarcoma, leukemias, neuroendocrine tumors or adenocarcinomas of the gastrointestinal
tract, and carcinomas of lung and endometrium were described to be the possible causes
of chylous ascites.[1 ]
As regarding the pancreas, chylous ascites was reported as a rare complication of
iatrogenic lesions of the lymphatic channels during cephalic duodenopancreatectomy
with extensive lymphadenectomy.[2 ] Postoperative lymphorrhagia is usually reversible within few days, spontaneously
or after administration of somatostatin analogues or octreotide.[11 ] Total parenteral nutrition associated with diuretics, medium chain triglycerides,
and removal of the drainage tube was also suggested.[2 ]
[12 ]
Even though it is not the most common cause of chylous ascites, PDAC can cause it
via lymphangiosis carcinomatosa, respectively obstruction and disruption of lymphatic
channels flow. Representing one of the most lethal tumors worldwide, PDAC is the 12th
most common encountered cancer worldwide, with an incidence of 4.2 per 100,000 and
over 330,400 deaths per year.[13 ]
[14 ] Fewer than 20% of PDACs prove to be surgically resectable at the time of diagnosis.[13 ]
As the lymph node metastasis is the most significant prognostic factor of PDAC, in
a recent study, the possible prognostic role of the degree of lymphatic vessel invasion
was emphasized.[14 ] It was proved that except lymph node metastasis, presence of tumor emboli in at
least five lymphatic vessels is a negative prognostic factor of locally advanced surgically
resectable PDAC of the pancreatic head. Moreover, presence of emboli in at least nine
lymphatic vessels, like our case, were comparable to or surpassed the significance
of lymph node metastasis.[14 ] In patients without lymph node metastases but tumor cells in at least 10 lymphatic
vessels, the survival rate was similar with those having positive lymph nodes.[14 ]
A grading system of lymphatic invasion (ly) was proposed by the Japan Pancreatic Society,
which suggested to be used in daily diagnosis and classify cases based on the following
four-tier code: ly0 (no evidence of invasion), ly1 (slight invasion), ly2 (moderate
invasion), and ly3 (marked invasion).[14 ]
[15 ]
Besides the lymphangiosis carcinomatosa, another aggressive indicator was the histological
aspect of the tumor cells. The primary tumor showed tubular structures, but plasmacytoid
morphology was seen in the tumor emboli and lymph node metastases. Although rare,
gastroenteropancreatic plasmacytoid carcinomas are considered high grade tumors, which
aggressivity seems to be induced by the epithelial mesenchymal transition (EMT) phenomenon
revealed by loss of E-cadherin and nuclear translocation of β-catenin due to alteration
of the Wnt/β-catenin pathway.[7 ]
[16 ]
[17 ] It was recommended to call these tumors as “mesenchymal-type poorly cohesive carcinomas”[7 ]. Only 10 cases of gastrointestinal carcinomas with plasmacytoid appearance were
reported till 2020: seven of the stomach, two of the ampulla of Vater, and one in
the rectum.[7 ]
[16 ]
In pancreas, plasmacytoid morphology was described in cytologic specimens, in “lipid-rich
variant of pancreatic endocrine tumors”[18 ], fine needle aspirations of serous cystadenomas,[19 ] and clear cell variant of solid pseudopapillary neoplasms (SPN).[20 ]
[21 ] To our knowledge, no cases of PDAC with plasmacytoid features and chylous ascites
were described yet. As the present case involved the distal part of the pancreas like
the SPN, and the later type is mainly developed in the pancreatic tail as result of
the Wnt/β-catenin pathway disruption,[17 ]
[21 ] it can be supposed that the PDAC with plasmacytoid component can be an aggressive
variant of pancreatic SPN.
Independently by localization, the plasmacytoid carcinomas are known to be predisposed
to intraperitoneal spread and carcinomatous ascites[7 ]
[22 ] like our case. In patients with PDAC, the amount of chylous fluid is usually small
preoperatively and CT scan might fail to identify it. In suspected cases, diagnosis
is mainly based on lymphoscintigraphy with 99m Technetium-labeled human albumin.[8 ] If it is detected preoperatively, the case is usually inoperable and peritoneo-venous
shunt is the therapy of choice.[23 ] To decrease the secretion of chylous fluid, the administration of furosemide and
somatostatin analogs or octreotide—with/without etilefrine—is indicated.[11 ]
[23 ] Low-fat diet, total parenteral nutrition, or other conservative methods are also
recommended.[11 ]
[23 ] In these patients, however, after shunting, the quality of life or survival period
are not significantly improved.
The present case highlights the need for a more attentive preoperative evaluation
of patients with PDAC and at the same time, the negative role of associated chylous
ascites, in these patients.
No data were published yet regarding the relation between the number of involved lymphatic
vessels and risk of chylous ascites even about the minimum number of lymphatic vessels
with tumor emboli that can be used as a negative prognostic factor, in patients with
PDAC of the pancreatic tail.
