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Endometrioid carcinoma of the endometrium with an invasive component of minimal deviation carcinoma
HUMAN PATHOLOGY
Volume 33, No. 8 (August 2002)
ENDOMETRIOID CARCINOMA OF THE ENDOMETRIUM WITH AN INVASIVE COMPONENT OF MINIMAL DEVIATION CARCINOMA KIEN T. MAI, MD, FRCPC, D. GARTH PERKINS, MD, FRCPC, HOSSEIN M. YAZDI, MD, FRCPC, AND JANE THOMAS, MD, FRCPC Minimal deviation endometrioid adenocarcinoma is a rare pathological variant of endometrioid adenocarcinoma. We describe a case representing another rare variant of endometrioid adenocarcinoma composed of both typical and minimal deviation endometrioid adenocarcinoma in a 45-year-old woman. Macroscopically, the cervix was of normal size but it had an indurated consistency. The myometrium was unremarkable. Microscopically, in addition to the typical endometrioid adenocarcinoma that involved 75% of the endometrium, there was a proliferation of mildly atypical endometrial type glands sparsely distributed in the fibrovascular tissue, typical of minimal deviation endometrioid adenocarcinoma. The latter component extended downward from the endomyometrial junction and involved focal areas of the uterine body and isthmus, diffusely invaded the entire cervix and
focally the cervical resection margins. Focal transitional areas between typical and minimal deviation endometrioid adenocarcinoma were identified. Due to a relatively normal gross appearance and the microscopic deceptively benign looking appearance, minimal deviation endometrioid adenocarcinoma may pose problems of obtaining adequate sampling and evaluating the thickness of invasion of the endometrial carcinoma on gross, as well as microscopic, examination. HUM PATHOL 33:856-858. Copyright 2002, Elsevier Science (USA). All rights reserved. Key words: minimal deviation, endometrioid adenocarcinoma, uterine cervix. Abbreviations: MDA-E, minimal deviation endometrioid adenocarcinoma of the endometrium; MDA, minimal deviation endometrioid adenocarcinoma; EA, endometrioid adenocarcinoma.
Minimal deviation endometrioid adenocarcinoma (MDA-E) is a rare pathological variant of endometrioid adenocarcinoma (EA) seen in the cervix and isthmus of the uterus.1-5 It is characterized by a proliferation of mildly atypical endometrial glands with no or minimal desmoplastic stromal reaction; therefore, the carcinoma is considered to be International Federation of Gynecology and Obstretrics (FIGO) grade 1 and nuclear grade 1. The lesion is difficult to discern on gross examination. Seven cases have been reported in the cervix and 3 in the isthmus.1-4 MDA-E has also been reported in the uterine corpus.5,6 We describe another variant of this rare entity, a mixed EA and MDA-E in which an EA formed within the endometrium and was accompanied by an invasive component having the features of MDA-E. The latter extensively infiltrated the cervix but only focally invaded the uterine body and isthmus. To investigate the frequency of this variant, we reviewed 75 consecutive cases of EA at our institution.
showed no evidence of adenomyosis. There was, however, a proliferation of mildly atypical endometrial type glands sparsely distributed in the fibrovascular tissue of the myometrium and the cervix characteristic of MDA-E. The tumor cells of this component often were of low columnar or cuboidal type with a few scattered ciliated glands. Mitotic figures were
CASE REPORT A 45-year-old woman presented with menometrorrhagia for 6 months. An endometrial biopsy specimen showed a proliferation of atypical endometrial glands consistent with EA. The patient subsequently underwent total hysterectomy and bilateral salpingo-oophorectomy. At postoperative follow-up of 3 months, the patient remained asymptomatic. On gross examination, the cervix was of normal size but was of indurated consistency. The endometrium showed thickening with the formation of several sessile polyps up to 1.0 cm in diameter. The myometrium was unremarkable. Microscopically, EA was seen to involve 75% of the endometrium of the uterine body and isthmus. Myometrium
From the Department of Laboratory Medicine, Division of Anatomical Pathology, The Ottawa Hospital–Civic Campus, and the Department of Pathology and Laboratory Medicine, University of Ottawa, Ontario, Canada. Accepted for publication April 1, 2002. Address correspondence and reprint requests to Dr. Kien T. Mai, MD, FRCP, Department of Anatomical Pathology, The Ottawa Hospital– Civic Campus, 1053 Carling Ave, Ottawa, Ontario, Canada, K1Y 4E9. Copyright 2002, Elsevier Science (USA). All rights reserved. 0046-8177/02/3308-0015$35.00/0 doi:10.1053/hupa.2002.126192
FIGURE 1. Section of the uterine body showing EA in the upper left and uppermost portions of the photomicrograph and MDA-E in the adjacent myometrium. (Inset) A gland of the MDA-E (indicated by the double arrowhead in the full photomicrograph), with minimal cytologic atypia, surrounded by the desmoplastic stroma.
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CASE STUDIES
FIGURE 2. Sections of the isthmus. (A) Section near the endometrial surface showing EA in the upper half of the photomicrograph and MDA-E in the adjacent myometrium. (Inset) A gland (indicated by the double arrowhead in the full photomicrograph) with transitional features between EA and MDA-E. (B) Section deep in the myometrium showing that MDA-E glands were distributed in the fibrous tissue between fascicles of smooth muscle. (Inset) A medium magnification of glands (indicated by the double arrowhead in the full photomicrograph).
rarely observed. There was dense eosinophilic secretory material in many glands. In the body of the uterus, MDA-E was focal (Fig 1). It extended downward from the endomyometrial junction and was limited to the inner one third of the myometrium. At the isthmus, MDA-E was again focal but invaded throughout out the entire thickness of the myometrium (Fig 2A and B). From the focal areas of the isthmus, MDA-E diffusely invaded the entire cervix (Fig 3) and extended to the lateral cervical resection margins. Focal transitional areas between typical EA and MDA-E were identified. Serial sectioning of the cervix and isthmus was performed to reconstruct the 3-dimensional appearance of MDA-E. The MDA-E glands rarely showed branching and followed a tortuous course in the perivascular space in the fibrovascular tissue (Fig 2B). Despite their sparse distribution in the tissue sections, they were in continuity with the neoplastic glands near the endocervical/endometrial surface. Similar histochemical and immunohistochemical properties were shown within EA and MDA. Both components showed positive luminal cell border staining for alcian blue and immunoreactivity for carcinoembryonic antigen, although the intraluminal secretory material was negative for these stains. The tumor cells showed positive reactivity for estrogen and progesterone receptors, vimentin, and cytokeratins AE1, AE3, and 7. Cytokeratin 20 and p53 were negative. MIB1 immunoreactivity was seen in fewer than 1% of the tumor cells in the MDA-E compared with more than 30% of tumor cells in the typical EA component.
A review of 75 consecutive cases of EA identified 1 case of MDA-E with oncocytic change. This case was reported previously.5 There were no other cases with focal or extensive MDA-E. DISCUSSION This case illustrates an example of MDA as the invasive component of a typical EA. This appears to be a rare phenomenon as shown by our failure to identify a similar case with a combination of EA and MDA in our review of 75 cases of typical EA. It is possible, however, that focal areas of MDA may be associated with typical EA. The 3 previously described cases of MDA 3,4 likely did not have a component of typical EA and MDA-E.5 Our previous report case as well consisted purely of MDA-E. In the report of 50 cases with diffusely invasive EA with adenoma malignum pattern of myoinvasin and 5 cases of diffusely infiltrating EA, respectively,6,7 typical EA-admixed MDA-E as described and illustrated in this report was not mentioned. In the study of 5 cases of diffusely infiltrating EA,7 the average FIGO grade of the diffusely infiltrating EA was 1.8 (compared with FIGO grade 1 and nuclear grade 1 in the present case). In these 2 reports, the proportion of cases that qualified as pure MDA-E and those that qualified as mixed typical EA and MDA-E was not specified. On examination of the hysterectomy specimen, areas of MDA-E may be overlooked because of the deceptively benignlooking appearance of the lesion. The diagnosis of MDA-E is
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HUMAN PATHOLOGY
Volume 33, No. 8 (August 2002)
The lesion must be distinguished from adenomyosis which is often associated with EA and is characterized by the presence of endometrial stroma; and a hyperplasia of mesonephric ducts, which occurs in the lateral portion of the cervix, is not associated with ciliated cells, and is not immunoreactive for estrogen and progesterone receptors.8 Because of the relatively normal gross appearance, the thickness of invasion of the endometrial adenocarcinoma, and therefore the tumor stage, cannot be correctly appreciated on gross examination. This may result in inadequate sampling of the invasive carcinoma. The 3-dimensional reconstruction of the MDA-E component in the present case showed the tumor cells’ propensity to grow along fibrovascular tissue in the perivascular space. The glands also show infrequent branching. Low proliferative activity was evidenced by the immunostaining for MIB1 in this case and the low mitotic rate reported in other cases.1 This may explain the sparsely distributed neoplastic MD glands in the stromal tissue. REFERENCES
FIGURE 3. Section of the uterine cervix showing diffuse involvement by MDA-E (Inset) High magnification of an MDA-E gland (indicated by the double arrowhead in the full photomicrograph) with ciliated epithelium.
based on the following criteria: (1) an invasive pattern without significant histopathologic atypia and (2) mild desmoplastic reaction of the stroma surrounding the neoplastic glands and an absence of surrounding endometrial stroma.
1. Young RH, Scully RE. Minimal-deviation endometrioid adenocarcinoma of the uterine cervix: A report of five cases of a distinctive neoplasm that may be misinterpreted as benign. Am J Surg Pathol 17:660-665, 1993 2. Rahilly MA, Williams AR, al-Nafussi A: Minimal deviation endometrioid adenocarcinoma of cervix: A clinicopathological and immunohistochemical study of two cases. Histopathology 20:351-354, 1992 3. Nanbu K, Konishi I, Yamamoto S, et al: Minimal deviation adenocarcinoma of endometrioid type may arise in the isthmus: Clinicopathological and immunohistochemical study of two cases. Gynecol Oncol 58:136-141, 1995 4. Masuda K, Yutani C, Akutagawa K, et al: Cytopathological observations in a 27-year-old female patient with endometrioid adenocarcinoma arising in the lower uterine segment of the uterus. Diagn Cytopathol 21:117-121, 1999 5. Mai KT, Yazdi HM, Boone SA. ‘Minimal deviation’ endometrioid carcinoma with oncocytic change of the endometrium. Arch Pathol Lab Med 119:751-754, 1995 6. Longacre TA, Hendrickson MR: Diffusely infiltrative endometrial adenocarcinoma: An adenoma malignum pattern of myoinvasion. Am J Surg Pathol 23:69-78, 1999 7. Mittal KR, Barwick KW: Diffusely infiltrating adenocarcinoma of the endometrium: A subtype with poor prognosis. Am J Surg Pathol 12:754-758, 1988 8. Silver SA, Devouassoux-Shisheboran M, Mezzetti TP, et al: Mesonephric adenocarcinomas of the uterine cervix: A study of 11 cases with immunohistochemical findings. Am J Surg Pathol 25:379-387, 2001
858
Volume 33, No. 8 (August 2002)
ENDOMETRIOID CARCINOMA OF THE ENDOMETRIUM WITH AN INVASIVE COMPONENT OF MINIMAL DEVIATION CARCINOMA KIEN T. MAI, MD, FRCPC, D. GARTH PERKINS, MD, FRCPC, HOSSEIN M. YAZDI, MD, FRCPC, AND JANE THOMAS, MD, FRCPC Minimal deviation endometrioid adenocarcinoma is a rare pathological variant of endometrioid adenocarcinoma. We describe a case representing another rare variant of endometrioid adenocarcinoma composed of both typical and minimal deviation endometrioid adenocarcinoma in a 45-year-old woman. Macroscopically, the cervix was of normal size but it had an indurated consistency. The myometrium was unremarkable. Microscopically, in addition to the typical endometrioid adenocarcinoma that involved 75% of the endometrium, there was a proliferation of mildly atypical endometrial type glands sparsely distributed in the fibrovascular tissue, typical of minimal deviation endometrioid adenocarcinoma. The latter component extended downward from the endomyometrial junction and involved focal areas of the uterine body and isthmus, diffusely invaded the entire cervix and
focally the cervical resection margins. Focal transitional areas between typical and minimal deviation endometrioid adenocarcinoma were identified. Due to a relatively normal gross appearance and the microscopic deceptively benign looking appearance, minimal deviation endometrioid adenocarcinoma may pose problems of obtaining adequate sampling and evaluating the thickness of invasion of the endometrial carcinoma on gross, as well as microscopic, examination. HUM PATHOL 33:856-858. Copyright 2002, Elsevier Science (USA). All rights reserved. Key words: minimal deviation, endometrioid adenocarcinoma, uterine cervix. Abbreviations: MDA-E, minimal deviation endometrioid adenocarcinoma of the endometrium; MDA, minimal deviation endometrioid adenocarcinoma; EA, endometrioid adenocarcinoma.
Minimal deviation endometrioid adenocarcinoma (MDA-E) is a rare pathological variant of endometrioid adenocarcinoma (EA) seen in the cervix and isthmus of the uterus.1-5 It is characterized by a proliferation of mildly atypical endometrial glands with no or minimal desmoplastic stromal reaction; therefore, the carcinoma is considered to be International Federation of Gynecology and Obstretrics (FIGO) grade 1 and nuclear grade 1. The lesion is difficult to discern on gross examination. Seven cases have been reported in the cervix and 3 in the isthmus.1-4 MDA-E has also been reported in the uterine corpus.5,6 We describe another variant of this rare entity, a mixed EA and MDA-E in which an EA formed within the endometrium and was accompanied by an invasive component having the features of MDA-E. The latter extensively infiltrated the cervix but only focally invaded the uterine body and isthmus. To investigate the frequency of this variant, we reviewed 75 consecutive cases of EA at our institution.
showed no evidence of adenomyosis. There was, however, a proliferation of mildly atypical endometrial type glands sparsely distributed in the fibrovascular tissue of the myometrium and the cervix characteristic of MDA-E. The tumor cells of this component often were of low columnar or cuboidal type with a few scattered ciliated glands. Mitotic figures were
CASE REPORT A 45-year-old woman presented with menometrorrhagia for 6 months. An endometrial biopsy specimen showed a proliferation of atypical endometrial glands consistent with EA. The patient subsequently underwent total hysterectomy and bilateral salpingo-oophorectomy. At postoperative follow-up of 3 months, the patient remained asymptomatic. On gross examination, the cervix was of normal size but was of indurated consistency. The endometrium showed thickening with the formation of several sessile polyps up to 1.0 cm in diameter. The myometrium was unremarkable. Microscopically, EA was seen to involve 75% of the endometrium of the uterine body and isthmus. Myometrium
From the Department of Laboratory Medicine, Division of Anatomical Pathology, The Ottawa Hospital–Civic Campus, and the Department of Pathology and Laboratory Medicine, University of Ottawa, Ontario, Canada. Accepted for publication April 1, 2002. Address correspondence and reprint requests to Dr. Kien T. Mai, MD, FRCP, Department of Anatomical Pathology, The Ottawa Hospital– Civic Campus, 1053 Carling Ave, Ottawa, Ontario, Canada, K1Y 4E9. Copyright 2002, Elsevier Science (USA). All rights reserved. 0046-8177/02/3308-0015$35.00/0 doi:10.1053/hupa.2002.126192
FIGURE 1. Section of the uterine body showing EA in the upper left and uppermost portions of the photomicrograph and MDA-E in the adjacent myometrium. (Inset) A gland of the MDA-E (indicated by the double arrowhead in the full photomicrograph), with minimal cytologic atypia, surrounded by the desmoplastic stroma.
856
CASE STUDIES
FIGURE 2. Sections of the isthmus. (A) Section near the endometrial surface showing EA in the upper half of the photomicrograph and MDA-E in the adjacent myometrium. (Inset) A gland (indicated by the double arrowhead in the full photomicrograph) with transitional features between EA and MDA-E. (B) Section deep in the myometrium showing that MDA-E glands were distributed in the fibrous tissue between fascicles of smooth muscle. (Inset) A medium magnification of glands (indicated by the double arrowhead in the full photomicrograph).
rarely observed. There was dense eosinophilic secretory material in many glands. In the body of the uterus, MDA-E was focal (Fig 1). It extended downward from the endomyometrial junction and was limited to the inner one third of the myometrium. At the isthmus, MDA-E was again focal but invaded throughout out the entire thickness of the myometrium (Fig 2A and B). From the focal areas of the isthmus, MDA-E diffusely invaded the entire cervix (Fig 3) and extended to the lateral cervical resection margins. Focal transitional areas between typical EA and MDA-E were identified. Serial sectioning of the cervix and isthmus was performed to reconstruct the 3-dimensional appearance of MDA-E. The MDA-E glands rarely showed branching and followed a tortuous course in the perivascular space in the fibrovascular tissue (Fig 2B). Despite their sparse distribution in the tissue sections, they were in continuity with the neoplastic glands near the endocervical/endometrial surface. Similar histochemical and immunohistochemical properties were shown within EA and MDA. Both components showed positive luminal cell border staining for alcian blue and immunoreactivity for carcinoembryonic antigen, although the intraluminal secretory material was negative for these stains. The tumor cells showed positive reactivity for estrogen and progesterone receptors, vimentin, and cytokeratins AE1, AE3, and 7. Cytokeratin 20 and p53 were negative. MIB1 immunoreactivity was seen in fewer than 1% of the tumor cells in the MDA-E compared with more than 30% of tumor cells in the typical EA component.
A review of 75 consecutive cases of EA identified 1 case of MDA-E with oncocytic change. This case was reported previously.5 There were no other cases with focal or extensive MDA-E. DISCUSSION This case illustrates an example of MDA as the invasive component of a typical EA. This appears to be a rare phenomenon as shown by our failure to identify a similar case with a combination of EA and MDA in our review of 75 cases of typical EA. It is possible, however, that focal areas of MDA may be associated with typical EA. The 3 previously described cases of MDA 3,4 likely did not have a component of typical EA and MDA-E.5 Our previous report case as well consisted purely of MDA-E. In the report of 50 cases with diffusely invasive EA with adenoma malignum pattern of myoinvasin and 5 cases of diffusely infiltrating EA, respectively,6,7 typical EA-admixed MDA-E as described and illustrated in this report was not mentioned. In the study of 5 cases of diffusely infiltrating EA,7 the average FIGO grade of the diffusely infiltrating EA was 1.8 (compared with FIGO grade 1 and nuclear grade 1 in the present case). In these 2 reports, the proportion of cases that qualified as pure MDA-E and those that qualified as mixed typical EA and MDA-E was not specified. On examination of the hysterectomy specimen, areas of MDA-E may be overlooked because of the deceptively benignlooking appearance of the lesion. The diagnosis of MDA-E is
857
HUMAN PATHOLOGY
Volume 33, No. 8 (August 2002)
The lesion must be distinguished from adenomyosis which is often associated with EA and is characterized by the presence of endometrial stroma; and a hyperplasia of mesonephric ducts, which occurs in the lateral portion of the cervix, is not associated with ciliated cells, and is not immunoreactive for estrogen and progesterone receptors.8 Because of the relatively normal gross appearance, the thickness of invasion of the endometrial adenocarcinoma, and therefore the tumor stage, cannot be correctly appreciated on gross examination. This may result in inadequate sampling of the invasive carcinoma. The 3-dimensional reconstruction of the MDA-E component in the present case showed the tumor cells’ propensity to grow along fibrovascular tissue in the perivascular space. The glands also show infrequent branching. Low proliferative activity was evidenced by the immunostaining for MIB1 in this case and the low mitotic rate reported in other cases.1 This may explain the sparsely distributed neoplastic MD glands in the stromal tissue. REFERENCES
FIGURE 3. Section of the uterine cervix showing diffuse involvement by MDA-E (Inset) High magnification of an MDA-E gland (indicated by the double arrowhead in the full photomicrograph) with ciliated epithelium.
based on the following criteria: (1) an invasive pattern without significant histopathologic atypia and (2) mild desmoplastic reaction of the stroma surrounding the neoplastic glands and an absence of surrounding endometrial stroma.
1. Young RH, Scully RE. Minimal-deviation endometrioid adenocarcinoma of the uterine cervix: A report of five cases of a distinctive neoplasm that may be misinterpreted as benign. Am J Surg Pathol 17:660-665, 1993 2. Rahilly MA, Williams AR, al-Nafussi A: Minimal deviation endometrioid adenocarcinoma of cervix: A clinicopathological and immunohistochemical study of two cases. Histopathology 20:351-354, 1992 3. Nanbu K, Konishi I, Yamamoto S, et al: Minimal deviation adenocarcinoma of endometrioid type may arise in the isthmus: Clinicopathological and immunohistochemical study of two cases. Gynecol Oncol 58:136-141, 1995 4. Masuda K, Yutani C, Akutagawa K, et al: Cytopathological observations in a 27-year-old female patient with endometrioid adenocarcinoma arising in the lower uterine segment of the uterus. Diagn Cytopathol 21:117-121, 1999 5. Mai KT, Yazdi HM, Boone SA. ‘Minimal deviation’ endometrioid carcinoma with oncocytic change of the endometrium. Arch Pathol Lab Med 119:751-754, 1995 6. Longacre TA, Hendrickson MR: Diffusely infiltrative endometrial adenocarcinoma: An adenoma malignum pattern of myoinvasion. Am J Surg Pathol 23:69-78, 1999 7. Mittal KR, Barwick KW: Diffusely infiltrating adenocarcinoma of the endometrium: A subtype with poor prognosis. Am J Surg Pathol 12:754-758, 1988 8. Silver SA, Devouassoux-Shisheboran M, Mezzetti TP, et al: Mesonephric adenocarcinomas of the uterine cervix: A study of 11 cases with immunohistochemical findings. Am J Surg Pathol 25:379-387, 2001
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