| Abstract|| |
Dedifferentiated endometrioid carcinoma or dedifferentiated endometrioid adenocarcinoma (DEAC) is defined by the presence of undifferentiated carcinoma with endometrioid carcinoma. Undifferentiated component can be misinterpreted as solid component of high-grade endometrioid carcinoma or sarcomatous component of malignant mixed mullerian tumor. We present two cases of DEAC. Two postmenopausal women underwent hysterectomy for vaginal bleeding. Microscopically, sections from the endometrial tumors showed a biphasic growth consisting of an undifferentiated component and a glandular component with sharp transition between the two components. The undifferentiated component showed focal positivity for cytokeratin and vimentin, while glandular component was diffusely positive for cytokeratin and negative for vimentin expression.
Keywords: Dedifferentiated endometrial carcinoma, dedifferentiated endometrioid carcinoma, endometrial carcinoma, malignant mixed mullerian tumor, undifferentiated carcinoma
|How to cite this article:|
Boler AK, Akhtar S, Bandyopadhyay A, Roy S. A report of two cases of dedifferentiated endometrioid carcinoma: A newly described underrecognized tumor of poor prognosis. Indian J Pathol Microbiol 2020;63, Suppl S1:91-3
|How to cite this URL:|
Boler AK, Akhtar S, Bandyopadhyay A, Roy S. A report of two cases of dedifferentiated endometrioid carcinoma: A newly described underrecognized tumor of poor prognosis. Indian J Pathol Microbiol [serial online] 2020 [cited 2020 Apr 5];63, Suppl S1:91-3. Available from: http://www.ijpmonline.org/text.asp?2020/63/5/91/279527
| Introduction|| |
Undifferentiated endometrial carcinoma can present as either pure form or mixed form. Mixed form is defined by association with a differentiated component. Mixed form is also known as dedifferentiated carcinoma or combined carcinoma. Most commonly, the associated differentiated component is low-grade (Federation of Gynaecology and Obstetrics (FIGO) grade 1 or 2) endometrioid carcinoma, and occasionally grade 3 carcinoma can be present with the undifferentiated component., For diagnosing dedifferentiated endometrioid adenocarcinoma (DEAC) correctly, it is important to recognize the undifferentiated component, which may appear like solid component of grade 3 endometrioid carcinoma or spindle cells of carcinosarcoma. DEAC has a fulminant course and association with Lynch syndrome.,
| Case History|| |
Case report 1
A 48-year-old postmenopausal woman presented with vaginal bleeding for 3 months. Transvaginal ultrasonography (USG) showed thickened endometrium. Endometrial curettage revealed well-differentiated endometrioid carcinoma. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy. On gross examination, uterus and cervix measured 7 cm × 4 cm × 3 cm [Figure 1]a. Endometrial surface was irregular with a tumor in the upper part of endometrial cavity. The tumor invaded more than half of the myometrium near fundus and measured 2.5 cm in largest dimension. Ovaries, tubes and cervix were uninvolved, stage pT1bNxMx.
|Figure 1:(a) Case 1: specimen of uterus, cervix, and bilateral tubes with ovaries showing a tumor arising from upper part of endometrial cavity (b) Case 2: specimen of uterus showing uterine cavity filled with tumor |
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Microscopically, sections from the endometrial tumor displayed a biphasic growth pattern consisting of confluent endometrial glands and complex papillary pattern of proliferation, along with undifferentiated areas with brisk mitotic activity [Figure 2]a. These areas showed mostly round to oval cells in sheets. Rare rosette-like formations were noted among the undifferentiated cells. Rare foci showing spindling of cells were also seen. There was sharp demarcation between the well-differentiated component and undifferentiated areas. Lymphovascular invasion was noted. The tumor had invaded more than half of myometrial thickness. Immunohistochemistry in this case was done for epithelial membrane antigen (EMA), vimentin, and CK (cytokeratin) expression. Cytokeratin showed diffuse positivity for well-differentiated part and focal, dot-like positivity for the undifferentiated component [Figure 2]b. The undifferentiated part showed weak focal positivity for EMA and the well-differentiated part showed strong positivity for EMA [Figure 2]c. Vimentin expression was negative in well-differentiated part and focal positivity was seen in the undifferentiated part [Figure 2]d. The patient was disease-free for 3 months and then lost to follow-up.
|Figure 2:(a) Photomicrograph of histopathological section showing a biphasic tumor, H and E stain, ×10. (b) Photomicrograph showing diffuse cytokeratin positivity in the glandular component and patchy positivity in undifferentiated component. (c) Glandular component showing diffuse EMA positivity and undifferentiated component showing patchy positivity for EMA. (d) Myometrium showing strong positivity for vimentin; glandular component is negative, while undifferentiated component shows patchy positivity|
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Case report 2
A 50-year-old postmenopausal woman presented with vaginal bleeding for 2 months. USG showed a mass arising from the endometrium and filling up the whole of the endometrial cavity. Total hysterectomy with bilateral salpingo-oophorectomy was performed. On gross examination, uterus and cervix measured 12 cm × 6 cm × 5 cm. The cut surface showed a growth, measuring 9 cm in largest dimension, arising from the fundus and occupying the entire endometrial cavity [Figure 1]b. Ovaries, tubes and cervix were unremarkable, stage pT1aNxMx. Microscopically, sections from the growth show histopathological features of a biphasic tumor with sharp transition between the two components. One part of the tumor showed glands arranged in confluent pattern, invading more than half of the myometrium, resembling grade 1 endometrioid carcinoma. The undifferentiated component was represented by dyshesive round to ovoid cells separated by delicate fibrovascular septa [Figure 3]a. There was high mitotic activity in the undifferentiated area. Immunohistochemistry showed the tumor cells in the glandular component to be positive for estrogen receptor (ER) (patchy) and cytokeratin [Figure 3]b and negative for vimentin [Figure 3]c. The tumor cells in the undifferentiated component showed focal intense positivity for cytokeratin; focal positivity for vimentin and was negative for ER. The patient was disease-free for 1 month after the initial diagnosis and then lost to follow-up.
|Figure 3: (a) Photomicrograph of histopathological section from the tumor H and E stain, ×10. (b) Glandular component showing diffuse CK positivity, undifferentiated component showing focal CK positivity. (c) Glandular component is negative for vimentin, while undifferentiated component is focally positive|
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| Discussion|| |
Undifferentiated carcinoma of the endometrium is a poorly recognized neoplasm, defined by World Health Organization (WHO) as malignant tumor of epithelial structures that is too poorly differentiated to be placed in any other category of carcinoma. As dedifferentiated carcinoma is a recently recognized tumor, the incidence rate is still not established. The prognosis of DEAC is determined by the undifferentiated component. The undifferentiated component can be misinterpreted as solid component of FIGO grade 3 endometrioid carcinoma. The morphologic appearance of DEAC also resembles undifferentiated endometrial sarcoma and malignant mixed mullerian tumors (MMMTs). DEAC has a worse prognosis in comparison to high-grade endometrioid carcinoma.
The solid component of high-grade endometrioid carcinoma shows focal glandular differentiation (1%–49% according to WHO); there is usually no abrupt demarcation between solid and glandular components; the cytological features of the cells of solid component and glandular component are similar; rhabdoid features are absent; there is diffuse positivity for CK and EM and positive expression of ER. The cytological features of undifferentiated and differentiated components are distinct in DEAC. Immunohistochemical expression of CK and EMA are diffusely positive in endometrioid carcinoma, whereas those are focally positive in undifferentiated component of DEAC. The undifferentiated component of dedifferentiated carcinoma usually shows absence of claudin-4 expression, while the differentiated component shows diffuse claudin-4 expression. Claudin-4 is an epithelial tight junction protein and it is always absent in sarcoma.
In MMMT or carcinosarcoma, the epithelial component is usually a high-grade tumor, most commonly serous carcinoma. The sarcomatous component consists of pleomorphic spindle cells. Whereas in DEAC the undifferentiated component consists of cells that are more plump and spindling is not that prominent. The epithelial component of DEAC is usually low-grade (FIGO grade 1 or 2) endometrioid carcinoma. Immunohistochemically, the undifferentiated component of DEAC will show only focal positivity for vimentin along with focal positivity for cytokeratin.
Undifferentiated carcinoma and DEAC are associated with DNA mismatch repair defect and Lynch syndrome., So, diagnosing DEAC correctly has an impact on identifying the genetic condition, genetic counseling, and work-up of family members who may also be affected by the same genetic defect. Recent studies have shown that undifferentiated carcinomas are frequently positive for programmed death ligand 1, and it suggests that immunotherapy may be considered as adjuvant in undifferentiated carcinoma showing programmed death ligand 1 positivity specially because there is poor response to traditional therapy.
| Conclusion|| |
DEC is frequently misdiagnosed as high-grade endometrioid adenocarcinoma and MMMT, but it has a fulminant clinical course, grave prognosis, and genetic defects; and misdiagnosis of this rare condition will have an adverse effect on patient's survival.
Informed written consents were obtained from the patients for the publication of this case report along with the images.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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