An indeterminate mucin-producing cystic neoplasm containing an undifferentiated carcinoma with osteoclast-like giant cells: a case report of a rare association of pancreatic tumors

International Consensus Guidelines have established how to diagnose and manage pancreatic
cystic tumors 7]. Although their clinical, radiological and pathological features have been defined,
in some cases the differential diagnosis between mucinous forms is difficult 8].

In our case the assessment of a correct preoperative diagnosis was difficult due to
the clinical and radiological findings. Patient’s age and main duct dilatation were
elements in favor of IPMN, while female gender and the involvement of the body of
the gland leaned towards MCN. However the diagnosis of IPMN was excluded as there
was no communication between the cystic mass and the main pancreatic duct.

Tumor size, peripheral calcifications, irregular septa, and the presence of an intramural
nodule pointed towards malignant transformation and led to surgical resection. Indeed
all these radiological findings are very frequently associated with malignant histology
9].

On the basis of microscopic criteria (nuclear atypia, number of mitoses, and invasion
into the stroma), the lesion should be categorized as a mucinous cystoadenocarcinoma.
Nevertheless the absence of ovarian-type stroma made us to classify it as an indeterminate
mucin-producing cystic neoplasm of the pancreas 7]. In the literature the lack of ovarian-type stroma is more frequent in postmenopausal
women and MCNs that do no express ovarian-type stroma have a worse prognosis compared
to those which have ovarian-type stroma 2], 10].

OGCC is rare pancreatic neoplasm: a US population study based on Surveillance, Epidemiology
and End Result (SERR) database evidenced that its incidence is 11 % of all undifferentiated
carcinomas of the pancreas 11].

In the past decades the histogenesis of OGCC was debated, but the more recent immunohistochemical
studies demonstrate that OGCs present no reactivity to epithelial markers and show
a positive reactivity to histiocytic marker CD68; by contrast, spindle-shaped mononuclear
cells express epithelial markers 12], 13]. The immunoreactivity for Ki-67 reveals a low proliferative activity of OGCs and
a high proliferative activity for mononuclear cells 13]. These data, as our findings, confirm the hypothesis that spindle-shaped mononuclear
cells are neoplastic elements, while OGCs are not neoplastic and may have a histiocytic
lineage 12], 13].

In our case numerous PGCs were detected in the solid area of the neoplasm. These cells
are frequently characterized by immunoreactivity for epithelial markers like cytokeratins
and CEA and by a high proliferative index; in some cases, PGCs express mesenchymal
markers like vimentin 14]. These data support the hypothesis that PGCs are undifferentiated neoplastic cells
derived from epithelial elements with a sarcomatoid profile. These histological changes
are typical of the epithelial-mesenchimal transition which is a marker of tumor de-differentiation
and invasiveness 15].

The simultaneous presence of PGCs and OGCs within the same tumor indicates a possible
overlap between the two histological types: some authors propose to classify the mixed
giant cell carcinoma as a different histopathological entity containing both osteoclastic
and pleomorphic giant cells in significant proportion 4], 14], 16].

Incongruous data is there in the literature about OGCC prognosis. Early reports based
on single case suggested that it might have a better outcome than ordinary ductal
carcinoma 17]. However in a series of nine cases all patients but one died within 1 year from diagnosis
12]. In a retrospective analysis of 15 patients with anaplastic carcinoma of the pancreas,
all long-term survivors presented a neoplasm containing OGCs and the median survival
was significantly better in this histological type 18]. In two small series, OGCCs with a high proportion of PGCs were associated with a
shorter survival 13], 19] and in an overall analysis of the few reported cases, the presence of a cell population
expressing epithelial markers seemed to predict a worse prognosis 20].

Ours is the second case described in the english literature of an indeterminate mucin-producting
cystic neoplasm containing an area of undifferentiated carcinoma with osteoclast-like
giant cells. In a review that analyzed all cases of MCN associated with OGCC, 10 of
12 patients were alive at follow-up 6]. By contrast our report was remarkable for the rapid progression of the tumor. It
is interesting to note that both cystic and solid components of the neoplasm presented
histological features of malignancy. Only further studies based on large series with
longer follow-up will clarify if the absence of ovarian-type stroma and the presence
of PGCs could be related with the outcome of these tumors.