2016, Volume 32, Number 2, Page(s) 126-129
Ovarian Yolk Sac Tumor with Granulomatous Reaction Resembling Tuberculosis A Unique Presentation
Shaista VASENWALA1, Noor Afshan SABZPOSH2, Hena ANSARI1, Nazima HAIDER1, Shazia PARVEEN2, Murad AHMED1
1Department of Pathology, Jawaharlal Nehru Medical College, AMU, ALIGARH, INDIA
2Department of Obstetrics and Gynaecology, Jawaharlal Nehru Medical College, AMU, ALIGARH, INDIA
Keywords: Ovary, Germ cell tumor, Granuloma, Giant cells
Yolk sac tumors (endodermal sinus tumors) are an important
subgroup of germ cell tumors of the ovary. They are seen in young
females and are highly aggressive, but respond well to treatment.
Although different morphological patterns can be seen on light
microscopy, granulomatous reaction and giant cells are a very rare
occurrence. We report the case of a young female with ovarian
yolk-sac tumor in which a widespread granulomatous reaction was
seen, causing a diagnostic dilemma.
Ovarian yolk sac tumors (YST) are malignant germ cell
tumors and are most common in children and young
females. They are rapidly growing aggressive tumors and
are characterized by elevated serum alpha-fetoprotein
(AFP) levels and a variety of histologic patterns. However,
the presence of giant cells and granulomatous reaction has
not been described in YST except for a rare association
with syncytiotrophoblastic giant cells1
. We report a case
of yolk sac tumor with extensive granulomatous reaction
showing numerous giant cells of Langhans type and tumor
giant cells. This pattern of YST has not been documented
before to the best of our knowledge.
A 21-year old woman, married for four months, nulligravida,
with irregular menstrual cycle and oligomenorrhoea,
presented with complaint of pain in abdomen for two
months. She was afebrile and mildly anaemic. There was
no jaundice and lymphadenopathy. Systemic examination was unremarkable. A lump was palpable in right lower
abdomen. It was soft to firm, tender and 16-20 weeks
uterine size. Vaginal examination revealed fullness in
posterior fornix with a tense mass.
Investigations revealed hemoglobin = 10 gm%, total leucocyte
count = 12x109/l, differential cell count = polymorphs70%,
lymphocytes 20%, monocytes 5%, eosinophils
5%, erythrocyte sedimentation rate = 40mm at 1 hour.
Urine examination was negative for sugar, albumin and
blood. Microscopic examination of urine showed 3-4 pus
cells (neutrophils)/high power field and 1-2 red cells/high
power field. X-ray chest was normal.
Ultrasound examination of the abdomen showed a mass,
arising from right adnexa, 15 cms in diameter, with
heterogenous echotexture and central necrosis. Serum AFP
level was raised to 800 ng/ml and serum human chorionic
gonadotrophin (HCG) was negative.
Right sided salpingo-oopherectomy with appendicectomy
and resection of a part of omentum was performed. The ovarian tumor was a partially capsulated round mass,
15x10x5 cm in size, with slightly nodular glistening outer
surface. Cut surface was solid creamish-white with areas
of hemorrhage and necrosis in the center. Appendix was
6x1 cm in size. Omental tissue, 12x4 cm showed a 0.5 cm
solid white nodule. Formalin fixed, H&E stained sections
revealed a capsulated tumor with central necrosis and
hemorrhage. The viable tissue at periphery showed a mixed
pattern of yolk sac tumor (Figόre 1a-c). Most prominent
was the reticular pattern made up of clear cells with
malignant hyperchromatic, round nuclei, with irregular
borders in some nuclei, finely clumped chromatin and
small nucleoli. The other patterns were glandular structures
and Schiller- Duval bodies. Numerous giant cells with
peripherally arranged and also centrally placed nuclei
representing granulomatous reaction were scattered evenly throughout the tumor parenchyma and were associated
with all the patterns of YST (Figure 1b-d). The nuclei of
giant cells resembled the tumor nuclei. A few epithelioid
cells and a thin rim of mature lymphocytes were seen
around some of the giant cells. Caseous necrosis was not
seen. Periodic acid-Schiff stain (PAS) positive globules
were seen lying free and also inside the cell (Figure 2a).
Immunostain for AFP (FLEX polyclonal rabbit anti-human
Alpha-1-fetoprotein, code IS500, ready to use, DAKO,
Denmark) was only focally positive (Figure 2b-D). The
giant cells showed diffuse and strong positivity positively
for CD68 (Clone KP-1, catalog no. PM 033AA, ready to
use, Biocare Medical, USA) (Figure 3A-C), supportive of a
monocytic macrophage origin. Nodule in omental tissue
showed focus of YST with giant cells. Appendix showed
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|Figure 1: a-c) Sections of YST showing sheets of malignant cells, Schiller-Duval bodies, glands and hyaline globules, and reticular
pattern with scattered giant cells (H&E; 10x). d) Langhans' type giant cell with peripherally arranged and also centrally placed nuclei
Click Here to Zoom
|Figure 2: a) Intra and extracytoplasmic PAS positive globules in YST (PAS; x10). b-D) Immunostaining for AFP showing focal positivity.
Click Here to Zoom
|Figure 3A-C: Immunostain for CD68 showing positivity in cytoplasm of giant cells in tumor areas.
As tuberculosis is prevalent in our country the patient
was investigated for co-existent tuberculosis. Mantoux
test and serum IgG- IgM antibodies for tuberculosis were
negative. All the sections of the tumor were negative for
acid fast bacilli (AFB). There was no lymphadenopathy
and X-ray chest was normal. A diagnosis of yolk sac tumor
with granulomatous giant cell reaction with metastasis in
omentum was made.
Varied architectural patterns can be identified on light
microscopy in yolk sac tumours (YST). Associated features
include Schiller-Duval bodies and hyaline globules.
Although syncytiotrophoblastic giant cells have rarely
been described in YST1,
other types of giant cells or
granulomatous reaction have not been reported in YST
to the best of our knowledge. In the case under study, we
found a profound granulomatous reaction in the form of
evenly distributed giant cells with peripheral and centrally
placed nuclei, morphologically resembling the nuclei of
tumor cells, which is a unique phenomenon. Occasional
giant cells were surrounded by a few epithelioid cells and a
rim of lymphocytes. No caseous necrosis could be made out
in the granulomas. The ischemic necrosis and hemorrhage
was confined to the central part of the tumor.
The differential diagnosis of a granulomatous reaction
in the ovary includes infections, especially tuberculosis,
and non-infective lesions such as sarcoidosis, Crohn's
disease, xanthogranulomatous oophritis, foreign body
and post-operative granulomas2-8. Tuberculosis is an
important cause of infertility and tubo-ovarian mass in
India. Therefore, it was necessary to rule out tuberculosis
in this patient. The investigations did not reveal any
tubercular focus. Sarcoidosis was excluded as there was
no lymphadenopathy and X-ray chest was normal. There
were no symptoms related to the gastro-intestinal tract
suggestive of Crohn's disease.
Giant cells and granulomatous reactions have been
described in other ovarian tumors. Syncytiotrophoblastic
giant cells have been found in dysgerminomas and
embryonal cell carcinomas9,10. These are usually
positive for HCG. The giant cells in this case were diffusely
and strongly positive for the marker CD68 (KP-1). CD68
is a 110-kilodalton glycoprotein which is associated with
lysosomes, and is present in the cytoplasm of several cells,
including monocytes and macrophages11,12. The results
indicate that the giant cells were of macrophage lineage and
reactive in origin.
Giant cells have also been found in the walls of ovarian
mucinous and rarely serous cystic neoplasms13,14. Benign multinucleated giant cells in a background of
pleomorphic mononuclear cells have been described in
giant cell tumor of ovary, as well as sex cord stromal tumors
with malignant giant cells15,16. In our case, the histologic
picture is unique, showing reticular, glandular and Schiller-
Duval body patterns of YST and granulomatous reaction
comprising of reactive multinucleated giant cells which has
not been reported before.
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