Endometrial adenocarcinoma with osteoclastic giant cells in stroma: a case report and review of literature Shaista M. Vasenwala, Shaham Beg, Hena A. Ansari, Nazima Haider & Rajyashri Sharma Archives of Gynecology and Obstetrics ISSN 0932-0067 Volume 285 Number 4 Arch Gynecol Obstet (2012) 285:1157-1160 DOI 10.1007/s00404-011-2089-1
1 23
Your article is protected by copyright and all rights are held exclusively by SpringerVerlag. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your work, please use the accepted author’s version for posting to your own website or your institution’s repository. You may further deposit the accepted author’s version on a funder’s repository at a funder’s request, provided it is not made publicly available until 12 months after publication.
1 23
Author's personal copy Arch Gynecol Obstet (2012) 285:1157–1160 DOI 10.1007/s00404-011-2089-1
G Y N E CO L O G IC O N C O L O G Y
Endometrial adenocarcinoma with osteoclastic giant cells in stroma: a case report and review of literature Shaista M. Vasenwala · Shaham Beg · Hena A. Ansari · Nazima Haider · Rajyashri Sharma
Received: 18 May 2011 / Accepted: 12 September 2011 / Published online: 25 September 2011 © Springer-Verlag 2011
Abstract It is rare to Wnd osteoclastic giant cells (OGCs) as a stromal reaction in uterine adenocarcinoma of endometrium. Here, we report a case of a 60-year-old female diagnosed with adenocarcinoma of endometrium. Total hysterectomy with bilateral salpingo-oopherectomy and removal of pelvic lymphnodes was performed. Histologically, the tumour showed adenocarcinoma of the endometrium with mucin secretion. The stroma showed some plump reactive pleomorphic cells, resembling stromal cells, inWltrated uniformly with OGCs and mononuclear cells (MNCs). The epithelial cells of adenocarcinoma stained positive for cytokeratin (CK 7) (CAM 5.2). The osteoclastic giant cells and mononuclear cells stained positive with CD68 and negative with cytokeratin and vimentin. We conclude that the osteoclastic giant cells originated from reactive histiocytes/monocytes as a stromal reaction to malignancy. Keywords Stromal reaction in endometrial adenocarcinoma · Osteoclastic giant cells
Introduction The presence of giant cells in the stroma of endometrial adenocarcinoma is a rare Wnding. These giant cells may be true tumour giant cells or they may be reactive in origin. Although the concurrent presence of such reactive giant cells in endometrial adenocarcinoma does not aVect the therapy or prognosis of the disease, it may present as a diagnostic problem to the pathologists. The diVerential diagnosis includes various uterine epithelial neoplasms with giant cells, such as carcinosarcoma, the very rare endometrial adenocarcinoma with a component of giant cell carcinoma, endometrial stromal sarcomas and infrequently, trophoblastic tumours [1]. Here, we report such a case of endometrial adenocarcinoma with giant cell reaction in the stroma. The major entities in the diVerential diagnosis are also discussed and we have highlighted the role of immunochemistry in resolving such diagnostic issues.
Case report
S. M. Vasenwala · S. Beg · H. A. Ansari (&) · N. Haider The Department of Pathology, Jawaharlal Nehru Medical College, AMU, Aligarh 202002, UP, India e-mail:
[email protected] R. Sharma The Department of Obstetrics and Gynaecology, Jawaharlal Nehru Medical College, AMU, Aligarh 202002, UP, India
A 60-year-old, multiparous post-menopausal female presented with complaints of foul smelling discharge and bleeding per vaginum (P/V) oV and on for the last 2 months. The parity was P (4+3). Patient was hypertensive and non-diabetic. Family history of malignancy could not be obtained. The uterus appeared bulky and mobile on per vaginum and per rectal examination. Routine examination showed anaemia (haemoglobin 5 g/dl), total cell count 17,000 cells/cumm, diVerential cell count polymorphs 75%, lymphocytes 20%, eosinophils 3%, monocytes 2% and erythrocyte sedimentation rate 50 mm/1st h. Urine showed traces of albumin (1+). Papanicolaou smear
123
Author's personal copy 1158
Arch Gynecol Obstet (2012) 285:1157–1160
showed heavy non-speciWc acute inXammation. On ultrasonography of the abdomen and pelvis, the uterus was globular with nodular surface and a hypoechoic mass Wlling the endometrial cavity and obliterating the junction of endometrium and myometrium was reported. A provisional diagnosis of endometrial carcinoma was made. Total hysterectomy with bilateral salpingo-oopherectomy with removal of two parametrial lymph nodes and sampling of pelvic fat was done. Gross examination The uterus and cervix measured 13 £ 10 £ 7 cm. On sectioning, six intramural and two cervical Wbroids measuring 0.4–8 cm in diameter were noted. The endometrial cavity was Wlled with a necrotic, haemorrhagic, friable mass of 5 cm in diameter which inWltrated into the myometrium. Light microscopy On histopathology, the tumour showed an extensive complex glandular pattern featuring branched neoplastic endometrial glands. The glands were lined by mucin-secreting columnar cells with malignant nuclei (Fig. 1). The solid area of malignant cells comprised 30% of the tumour area. The nuclei were enlarged, pleomorphic, hyperchromatic with increased N/C ratio, irregular margins, clumped chromatin and prominent nucleoli. Increased mitotic rate of 5– 6/10 HPF was seen. The cytoplasm of the cells was lightly stained and periodic acid-SchiV (PAS) positive. The stroma showed prominent plump spindle cells of varying shapes and apparently hyperchromatic nuclei, resembling stromal cells. Osteoclastic giant cells with 10– 20 nuclei were uniformly scattered in the stroma and mononuclear cells were also seen. Mitosis was not evident in the stroma. The tumour inWltrated 60% of the thickness of the myometrium. Leiomyomas comprised bands and whorls of smooth muscle inWltrated focally by endometrial carcinoma. Lymphatic and vascular invasion by the tumour was not seen. Rest of the tissue was unremarkable. The two parametrial lymph nodes showed reactive sinus histiocytosis. The biopsied fat was also negative for any malignancy. A provisional diagnosis of endometrial carcinosarcoma of the uterus was made. Immunohistochemically, the epithelial lining of the mucin-secreting glands and cell groups of adenocarcinoma stained positive with cytokeratin (CK 7) (CAM 5.2) while giant cells and mononuclear cells stained positive for CD68 and negative for CK7(CAM 5.2) and vimentin (Figs. 2, 3, 4). The positive staining pattern of the giant cells for CD68 revealed them to be of histiocytic origin. Prominent cells in the stroma, which resembled stromal cells were both CK and vimentin negative. (Fig. 3).
123
Fig. 1 Tightly packed, dilated, mucin-secreting endometrial glands lined with malignant columnar cells, with stromal atypia and small osteoclastic giant cells (H&E, a £125, b £400)
Fig. 2 CK positive cells lining malignant endometrial glands (CK, £400)
After reviewing the Wndings, the Wnal diagnosis of endometrial adenocarcinoma with mucin secretion, grade 2, stage Ic, and with a stromal osteoclastic giant cell reaction was made.
Author's personal copy Arch Gynecol Obstet (2012) 285:1157–1160
1159
Discussion
Fig. 3 Cells in stroma are vimentin negative, smooth muscles of blood vessels are positive (vimentin, £100)
Fig. 4 OGCs and MNCs are CD68 positive, epithelial cells lining glands are negative (CD 68)
The patient received radiotherapy (50 Grays) administered as 5 cycles per week for 5 weeks. She has been followed-up monthly for 6 months and showed no signs of recurrence during this period.
Here, we discuss the spectrum of giant cell containing uterine neoplasms. The diVerential diagnosis of the above case mainly includes (1) uterine epithelial neoplasms with osteoclastic giant cells, (2) carcinosarcomas, (3) endometrial giant cell carcinoma, (4) endometrioid carcinoma with choriocarcinomatous diVerentiation. Imura et al. (2005) [2] reported a case of adenosquamous carcinoma of endometrium with osteoclast-like giant cells and inXammatory cells in stroma. Immunohistochemically, the osteoclastic giant cells and inXammatory cells stained strongly positive for KP-1(CD68) and -1-antichymotrypsin and negative for the epithelial markers, epithelial membrane antigen (EMA) and cytokeratins. Thus, the origin of osteoclastic giant cells from histiocytes/macrophages was suggested. Primary extraskeletal epithelial neoplasms with osteoclastic giant cells presenting as a stromal reaction are rare. The cases of carcinosarcoma show features of endometrial adenocarcinoma with malignant diVerentiation of stroma into cartilage, bone, fat etc. The epithelial and stromal cells possibly have the same origin as stromal cells often stain positive with epithelial markers. Interestingly, metastasis usually occurs in the form of an adenocarcinoma. [3]. Jones et al. (1991) [1] reported a series of six cases of endometrial adenocarcinoma with a malignant giant cell component. These were high grade, aggressive tumours with cohesive nests and sheets of multinucleated bizarre giant cells mixed with mononuclear tumour cells. Occasional tumour giant cells were CK (AE 1/AE3 or CAM 5.2) and epithelial membrane antigen (EMA) positive. A similar description of Wve cases was also published recently by Mulligan et al. [4] There have been rare reports of endometrial carcinomas with areas of choriocarcinomatous diVerentiation [5, 6] These tumours also exhibit pleomorphic giant cells of syncytiotrophobastic origin and, in contrast to osteoclastic giant cells, they are positive for beta-HCG. In conclusion, we report a case of adenocarcinoma endometrium, grade 2, stage Ic, with stromal giant cell reaction and inXammatory cells, staining positive for CD68 and negative for cytokeratin and vimentin, suggesting the origin of giant cells from histiocytes/macrophages, as a stromal reaction to the epithelial neoplastic component. ConXict of interest
None.
References 1. Jones MA, Young RH, Scully RE (1991) Endometrial adenocarcinoma with a component of giant cell carcinoma. Int J Gynaecol Pathol 10(3):260–270
123
Author's personal copy 1160 2. Imura J, Tomita S, Ono Y et al (2005) Endometrial adenosquamous carcinoma with osteoclast like giant cells: immunochemistry and histogenesis. APMIS 111(2):140–144 3. Silverberg SG et al (1990) Carcinosarcoma (malignant mixed mesodermal tumor of the uterus). Int J Gynaecol Pathol 9:1 4. Mulligan AM, Plotkin A, Rouzbahman M, Soslow RA, Gilks CB, Clarke BA (2010) Endometrial giant cell carcinoma: a case series and review of the spectrum of endometrial neoplasms containing giant cells. Am J Surg Pathol 34(8):1132–1138
123
Arch Gynecol Obstet (2012) 285:1157–1160 5. Akbulut M, Tosun H, Soysal ME, Oztekin O (2008) Endometrioid carcinoma of the endometrium with choriocarcinomatous diVerentiation: a case report and review of the literature. Arch Gynecol Obstet 278(1):79–84 6. Yamada T, Mori H, Kanemura M, Ohmichi M, Shibayama Y (2009) Endometrial carcinoma with choriocarcinomatous diVerentiation: a case report and review of the literature. Gynecol Oncol 113(2): 291–294
