2015, Volume 31, Number 3, Page(s) 219-222
Primary Gastric Invasive Micropapillary Carcinoma: A Case Report
Enver VARDAR1, Bengü GÜNAY YARDIM2, Rukiye VARDAR3, Mustafa ÖLMEZ4
1Department of Pathology, Bozyaka İzmir Training and Research Hospital, İZMİR, TURKEY
2Manisa State Hospital, İZMİR, TURKEY
3Ege University Faculty of Medicine, Department of Gastroenterology, İZMİR, TURKEY
4İzmir Tepecik Training and Research Hospital, Department of General Surgery, İZMİR, TURKEY
Keywords: Stomach neoplasms, Gastrointestinal neoplasms, Papillary carcinoma
Invasive micropapillary carcinoma is a recently identified
neoplasm. A 77-year-old-female was admitted to the hospital due
to progressive loss of weight and nausea. Endoscopic biopsy of
the antral/prepyloric located mass was diagnosed as moderately
differentiated adenocarcinoma. Subtotal gastrectomy and regional
lymph node resection were performed. The tumor was composed of
moderately differentiated cells arranged in micropapillary structures
with only a few poorly formed glandular foci in lamina propria.
Immunohistochemically, neoplastic cells of micropapillary and
focal conventional adenocarcinoma areas were diffusely positive
for pancytokeratin, cytokeratin 7 and epithelial membrane antigen.
In micropapillary areas, membranous and peripheral cytoplasmic
positivity with epithelial membrane antigen in outside of the cell
clusters called “inside-out polarity” pattern that is characteristic for
invasive micropapillary carcinoma were seen. Invasive micropapillary
carcinoma is very rare in the stomach in the English literature.
Invasive micropapillary carcinoma (IMPC) has been
recently identified as a characteristic variant of carcinoma
composed of small clusters of tumor cells located
within clear spaces1-8
. Initially, it was described as
an architecturally different variant of invasive breast
. In addition to highly interesting histological
and immunohistochemical features, this type of tumor has
a poor clinical prognosis due to the unique high incidence
of lymphatic invasion and axillary lymph node metastases2
. This entity has been reported in various sites other
than breast, including urinary bladder, lung, colon and
major salivary glands3-6
. IMPC of the bladder more
often appears in combination with conventional carcinoma
rather than a pure histological component3
. Herein we report a case of gastric IMPC, rarely reported in the
A 77-years-old-female who had been followed up for
hypertension and coronary arterial disease in outpatient
clinic for ten years, was admitted to hospital with the
complaints of nausea and loss of weight. In the gastric
endoscopy, an antral/prepyloric, ulcerated mass, 5 cm
in largest diameter has been observed and biopsied.
Endoscopic biopsy was diagnosed as moderately
differentiated adenocarcinoma. Among the tumor
markers, only carcinoembrionic antigen (CEA) was
increased (CEA:39.26 mg/dl., normal value: <2.5 mg/dl.).
Upper abdominal and pelvic ultrasonography (US) and thorax computerized tomography revealed no metastatic
lesion, preoperatively. Distal subtotal gastrectomy and
regional lymph node resection were performed. Adjuvant
chemotherapy were planned due to the presence of residual
tumor in peritoneum, but could not be applied due to
advanced age and cardiac problems. The patient is being
followed up by US and CEA levels for eight months.
Macroscopically, the 5 cm ulcerated tumor was located in
the antral and pyloric transition region with an irregular
border. Microscopically, it was composed of moderate to
severe cytological atypical carcinoma cells, arranged in
micropapillary structures. In superficial areas of ulcerated mass, transition from classical adenocarcinoma to IMPC
areas were seen abruptly (Figure 1). However over 90%
of the tumor was composed of micropapillary structures
(Figure 2) except for several foci of poorly differentiated
adenocarcinoma. Neoplastic cells invaded the muscularis
propria and subserosal adipose tissue and also foci of
lymphatic invasion were observed. Two of two lymph
nodes along the greater curvature, and six of nine lymph
nodes along the lesser curvature revealed metastases
composed of a mixture of micropapillary and conventional
adenocarcinoma morphologically contrary to primary
tumor (Figure 3).
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|Figure 1: Ulcerated surface, submucosal and muscularis propria
invasion were seen in adjacent to normal gastric glandular
epithelium (H&E; x20).
Click Here to Zoom
|Figure 2: High-power view showing micropapillary small clusters
of neoplastic cells lying within clear spaces. (H&E; x200).
Click Here to Zoom
|Figure 3: Mixture of classical adenocarcinoma and micropapillary
carcinoma areas in metastatic lymph node (H&E; x100).
Neoplastic cells of micropapillary and conventional
adenocarcinoma components were diffusely positive for
pancytokeratin, cytokeratin 7 (CK7) and EMA. On the
contrary of the positivity of EMA that was predominantly
observed in luminal surface and cytoplasm of glandular
structures in ordinary adenocarcinoma areas; outside
membranous and peripheral cytoplasmic positivity were
seen in micropapillary areas (Figure 4). This kind of staining
pattern is called “inside-out polarity” and is considered
highly characteristic for micropapillary carcinoma. The
possibility of fixation artefact versus vessel invasion was
verified by CD34 and factor VIII related antigen negativity.
Results of other immunohistochemical antibodies were
given in Table I. Approximately 35% of the neoplastic cells
were positive for Ki-67 antigen.
Click Here to Zoom
|Figure 4: Characteristic inside-out polarity staining pattern were
seen in immunohistochemistry for epithelial membrane antigen
IMPC is a rare entity, the most characteristic feature of
which is tufts of tumor cells arranged in pseudopapillary
patterns without fibrovascular cores. The tufts are
characteristically surrounded by clear spaces1-6
“inside-out” growth structure has been explained with
the rotation of cell polarization whereas the stroma-facing
surface of the cells obtaining apical properties3
. In the
present case, inside-out growth pattern has been proved
immunohistochemically with the anti-EMA antibody. It is
hypothesized that this reverse polarization in IMPC activates
the secretion of some molecules by the tumor cells, such as
metalloproteinases, which are suspected to be responsible
for stromal and vascular invasion, and propensity to easier
dissemination of tumor cells and a higher risk for lymph
The main differential diagnosis of primary IMPC of the
stomach is conventional gastric carcinomas showing extensive lymphatic invasion or metastatic invasive
micropapillary carcinomas8. In our case, lymphovascular
invasions have been ruled out with CD34 negativity in
lining cells in inner surface of spaces. We used three
criteria to distinguish the primary IMPC from a metastatic
carcinoma. Firstly, the presence of foci of ordinary
adenocarcinoma originated from the gastric mucosa
and the transition between classical adenocarcinoma
and IMPC areas. Secondly, absence of any radiologically
detected solitary or multiple masses compatible with
possible primary focus. And finally, immunohistochemical
staining profile of neoplastic cells which demonstrated
CK7 positivity, CK20, estrogen, progesteron, GCDFP-15
and cerbB-2 negativity pointing out the stomach as the
most possible primary site. Clinicopathological stage of
stomach IMPC is usually reported to be higher, that most
of the patients have invasion in gastric subserosal tissue in
addition to muscularis propria invasion and lymph node
metastasis similar to our case7-10. But, on the contrary,
Roh et al. suggested that the prognosis of the patients with
IMPC of the stomach were not different than the patients
with ordinary adenocarcinoma of the stomach11. Our
patient was under follow-up without any therapy due to
major cardiovascular problems. Although a minimum
increase of the CEA level (CEA:39.26 mg/dl. to 43.19 mg/
dl.) was observed in blood during follow-up, the patient
remained alive without further metastasis for eight months,
after the operation. But it is very early to judge about the
survival of the case for the limited follow up period.
The E-cadherin gene has been described as an invasionsuppressor
gene12 and the loss of E-cadherin expression
is considered to be associated with tumor invasion in gastric
adenocarcinomas. E-cadherin loss has also been reported
in primary gastric IMPC and one of the reported case also had a 23.5 % Ki-67 expression rate as a predictive marker
of poor prognosis12,13. In our case, loss of E-cadherin
expression was observed in both IMPC and poorly
differentiated component of the tumor similar to reported
by Shimoda et al8. Ki-67 index was 35% in neoplastic
cells and was similar again to results published in literature.
Agressive nature and high morbidity and mortality ratio
of the entity in stomach were also described in a recently
published paper by Ushiku et. al14. However larger series
with IMPC component is necessary to determine the actual
importance of the ratio of IMPC component and its impact
on the prognosis of gastric cancer.
In conclusion, the diagnosis of IMPC should be kept in
mind and needs to be carefully analyzed to understand its
etiopathogenesis and effect on clinical behaviour.
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