36, 321-326 (19%)
Endometrial Squamous Cell Carcinoma: Report of Three Cases and Review of the Literature VERA *Department
PH.D. t Montebello,
histopathologic review of 1993 casesof confirmed endometrial carcinoma produced two cases of primary squamous cell carcinoma. A third possible case is included to illustrate the diagnostic problems in this type of tumor. All patients presented with advanced disease and died within a year. The literature is reviewed and the criteria for acceptance of a diagnosis of endometrial squamous cell carcinoma are discussed. o ma Academic P~.s, IIK. A
Primary squamous cell carcinoma of the endometrium (ESCC) is exceedingly rare. Only sporadic cases have been reported, the first one by Gebhard in 1892 [l-3 11. Fluhmann  in 1928 recognized ESCC as a subgroup of endometrial carcinoma and proposed diagnostic criteria which include (I) no coexisting endometrial adenocarcinoma, (2) no connection between the endometrial tumor and the squamous epithelium of the cervix, and (3) no squamous cell carcinoma of the cervix (CSCC). WHO  has extended Fluhmann’s criteria by adding “There must be clear evidence of squamous differentiation such as intercellular bridges and/or keratin. A spindle cell form of squamous cell carcinoma is sometimes seen, as in the cervix.” Baggish and Woodruff  in 1967, Yamashina and Kobara  in 1986, and Simon and co-workers  in 1988 reviewed the literature and found 13, 28, and 26 cases of ESCC, respectively. We add another two cases in this paper. The literature is reviewed and previously reported observations are compared with our findings. PATIENTS
A 47-year-old premenopausal woman, para 2 gravida 3, complained of profuse vaginal bleeding. D&C showed squamous cell carcinoma (SCC). She was referred to the Norwegian Radium Hospital for treatment. Gynecological examination revealed a normal cervix and an enlarged uterine body. A fractional D&C showed fragments of a poorly differentiated SCC with a few keratinized cells exclusively in the endometrial fraction with normal endometrium adjacent to the tumor. Cervical scrapings and biopsies were negative. According to FIG0 staging rules the patient was classified as stage I. Laparotomy disclosed an inoperable uterine tumor, 12 cm in diameter, firmly adherent to the pelvic side wall. Metastases were suspected in the liver and in the pelvic and paraaortic lymph nodes. The right ovary and fallopian tube were removed and showed metastases from a poorly differentiated SCC. Sporadic cells showed keratinization and intercellular bridges. No intracellular mucin was found. External beam therapy (5000 rads) was given postoperatively to the pelvis. The patient died 5 months later as a result of thrombophlebitis and repeated episodes of pulmonary embolism. No autopsy was performed.
A total of 2090 cases of endometrial carcinoma were reported to The Norwegian Cancer Registry during the years 1970-1977, and 1999 of these were confirmed by histology. Three cases of ESCC were found. ’ To whom requests for reprints should be addressed.
A 61-year-old woman, para 4 gravida 4, menopause at the age of 50, suffered from vaginal discharge and bleeding for about a year before D&C showed SCC. The patient was referred to The Norwegian Radium Hospital. Gynecological examination was normal. A fractional D&C showed SCC restricted to the endometrial fraction. The patient was assigned to stage I. Abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy were performed. Histopathological examination showed a moderately differentiated keratin-
321 0090~8258/90 $I .50 Copyright 0 1990 by Academic Press, Inc. All rights of reproduction in any form reserved.
izing SCC in the uterine corpus (Fig, 1). Atrophic endometrial glands were seen adjacent to the tumor (Fig. 2). There was no evidence of adenocarcinoma. Occasional cells in a single sheet of obvious SCC carcinoma showed positive intracytoplasmic staining with Alcian green. The tumor infiltrated the outer part of the myometrium. Groups of tumor cells were seen in endothelium-lined spaces, consistent with lymphatic vessel invasion. The entire cervix was sectioned for histological examination, without revealing tumor involvement. Metastases were found in one pelvic lymph node. The ovaries and fallopian tubes were normal. External beam therapy to the pelvis was given postoperatively. After receiving 4000 rads, the patient developed intestinal obstruction which was treated by resection of a length of small bowel. Postoperatively her condition deteriorated and she died 3 months later. Autopsy showed peritonitis. No evidence of spread from ESCC was found.
ified as stage I. Abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Histopathological examination showed a moderately differentiated keratinizing ESCC. In small areas, normal endometrium was found to overly the tumor. There was no evidence of adenocarcinoma. The tumor infiltrated the myometrium to the serosa (Fig. 3), and groups of tumor cells were found in endothelium-lined spaces. Sections of the entire cervix and from the ovaries and fallopian tubes showed no tumor. Postoperatively, 5000 rads of external beam radiation was given to the pelvis. Four months later, the patient was readmitted with a large vaginal recurrence infiltrating to the pelvic wall and a rectovaginal fistula. She developed an intestinal obstruction which necessitated surgical intervention. The patient died 9 months later. No autopsy was performed.
The diagnosis of ESCC as defined by Fluhmann  and WHO  requires careful examination of the uterine body to rule out the presence of a component of adenocarcinoma or adenosquamous carcinoma. Further, the entire cervix should be sectioned for histological examination to exclude (1) a connection between the SCC in the corpus and the squamous epithelium of the ectocervix and (2) extension to the uterus from minor foci of SCC or in situ lesions of the cervix. According to these criteria it is impossible to confirm
A 6%year-old woman, para 2 gravida 4, menopause at the age of 55, was admitted with a history of vaginal discharge of l-month duration. A cervical smear was consistent with SCC. Gynecological examination revealed no gross abnormality, but histopathological examination of the endometrial fraction of the D&C material showed SCC. Endocervical tissue and a separate cervical biopsy showed no tumor. The patient was class-
FIG. 2. Area of squamous cell carcinoma adjacent to endometrium with atrophic glands-case
a diagnosis of ESCC in stage I patients who have been treated by preoperative irradiation and where no residual tumor is found in the operative specimen. The same is true when the tumor is inoperable. Thus, the two stage I cases with no tumor left in the hysterectomy specimen after preoperative irradiation (recorded by Kay [20, case 21 and Bibro et al. ), as
FIG. 3. Area of well-differentiated
well as the case reported by White et al.  and our case 1 (both inoperable stage IV tumors), cannot be inchided among cases with documented ESCC. Furthermore, case 1 reported by Kay  must be omitted from our revised list of reported ESCC (Table 1) because it showed squamous cell in situ lesions of the cervix and of the endometrium and numerous sites of SCC in the
squamous cell carcinoma infiltrating to the serosa-case
Primary Squamous Cell Carcinoma of the Endometrium: A Corrected and Updated List of Reported Cases” Gebhard [I] Flaischlen [Z] Batchelor and Doran  Norris  Spranger
I I I
1 I I
Hyst + BSO
50 59 78
None None Pyometra ago Inversion
Levine and Sciorsci [ 141 Maheshwari et al.
Ampution Pyometra None
Postop Rad Hyst + BSO Mastectomy Preop Rad Hyst + BSO Hyst + BSO
Hyst + BSO Hyst + BSO Hyst + BSO Preop Rad Hyst + BSO Postop Rad Hyst + BSO Deep Rad Preop Rad Hyst + BSO Postop Rad Preop Rad Hyst + BSO Hyst + BSO
Bellone [ 161 Hopkin et al. 
White et al. [I81
Pyometra R menopause years ago None
+ BSO + BSO
55 50 58 78
Cerv dysplasia None
Vyas CI a/. 1251 Lifschitz et al.  Ryder 
Alive 9 months Alive 2 months
I DOD 36 months
I N.S. Serosa N.S. Depth N.S. <&
1 1 I
1 I I
N.S. N.S. N.S. DOD 7 months Alive 6 months
I Alive 29 months
N.S. Depth N.S.
55 55 61
Curtin et al. 
Pyometra None Estrogen Pyometra None
Yamashina and Kobara 1301 Simon ef al. 
Breast cancer with metastases Rad to pelvis None
Preop Rad Hyst + BSO Hyst + BSO Postop Rad Hyst + BSO Hyst + BSO Postop Rad Hyst + BSO Hyst + BSO
Alive 4 months Dead of heart disease >24 months N.S. N.S.
I &rosa >$
Alive 24 months Alive 14 months N.S.
Hyst + BSO Hyst + BSO
Depth N.S. <$
Alive 7 months Alive 6 months
Hyst + Hyst + Postop Hyst +
BSO BSO Rad BSO
Alive >60 months
DOD 18 months Alive 42 months
Hyst f BSO
Alive 24 months
Hyst + Postop Hyst + Postop
r? BSO, bilateral salpingo-oophorectomy; NTL, no tumor left; Rad, irradiation;
R menopause years ago Estrogen None
Seltzer PI ul.  Taghinia and Nasirai 1221 Melin et al.  Datta and Gordon
DOD 3 months
I cm Serosa Serosa
Hyst Hyst Hyst
Williamson and Abercrombie  de Gery and Perrot  Wahi and Jain  Chu et a[.  Peris it al. [lo]
Pyometra Pyometra Pyometra
[ 1 I]
BSO Rad BSO Rad
DOD 4 months Alive 19 months
Dead of treatment 3 months DOD 9 months
DOD, dead of disease; Expl lap, explorative laparatomy; Hyst, hysterectomy; N.S., not stated; 4, infiltration in less than half the myometrial thickness; >2,1 mfiltration in more than half the myometrial
genital tract, but did not show invasive XC in the endometrium. Documentation of ESCC with extension to the cervix
is in most cases impossible. When both the cervix and the endometrium are involved, primary SCC of the cervix is the most likely diagnosis. Unless the infiltration
is limited to the upper part of the cervix, such cases should be registered as SCC of the cervix. The fact that no case of ESCC stage II disease has been reported reflects these diagnostic difficulties. Piering [361, in 1887, reported a case with a small SCC of the cervix and a separate large SCC in the corpus. He regarded the latter as the primary tumor. This case is also omitted from our revised list because a primary SCC of the cervix with metastases to the endometrium cannot be excluded. In the case reported by Taghinia and Nasirai [221 the ESCC infiltrated the outer layer of the cervix, but there were no neoplastic changes in the cervical mucosa. This case is therefore accepted as ESCC. In our cases 2 and 3, adenocarcinoma of the endometrium did not coexist, no malignancies or precancerous lesions were present in the cervix, and there was no connection between the ESCC and the squamous epithelium of the cervix. Intercellular bridges and keratinization were present in both tumors. One of our cases showed minor foci of intracellular mucin. According to WHO , the presence of minute amounts of intracellular mucin should not exclude the diagnosis of SCC. Thus, our two cases fulfil Fluhmann’s and WHO’s criteria for ESCC and bring the number of documented cases of ESCC to 31. Most ESCCs have been published as single case reports [l-3 11. Further, only selected cases have been accepted because of the strict criteria for the diagnosis of ESCC. It is thus hardly possible to obtain a reliable estimate of the true incidence. In our series of endometrial carcinoma, ESCC is the least frequent histologic type and accounts for 0.1% (211990) (0.15% if we include case 1). The histogenesis of ESCC is controversial. The most accepted theories are that the tumor cells originate in the endometrium through a process of squamous metaplasia or from an omnipotent “reserve cell” lying between the columnar epithelium and the basement membrane . Squamous metaplasia in the endometrium has been found in some of the reported cases [2,9,1517,21,25,30,31], but was not present in any of our cases. Squamous metaplasia in the endometrium is considered to be induced by various conditions that have been associated with ESCC. Some of the patients in the earlier years had pyometra [l-3,7,10,16,25,28,31], and a few had had uterine inversion [6,11]. Two cases followed a radium-induced menopause [17,19]; one had irradiation to the pelvis for metastases from a breast carcinoma [3 I] and two had received estrogen medication [21,28]. Vitamin A deficiency, instillation of chemicals into the uterine cavity, and curettage are also reported to induce squamous metaplasia . Most of the more recently reported cases, our three patients included, presented none of the mentioned conditions (Table 1).
Table 1 summarizes the main clinical findings and follow-up of 31 patients with ESCC gathered from the literature, including our cases 2 and 3. The average age of the 31 patients is 62.7 years (range, 47-85), practically the same as that for all patients with confirmed endometrial carcinoma in Norway during the years 1970 to 1977 (62.0 years). As must be expected from the criteria used for diagnosis, most of the reported patients were in clinical stage I (30/31, Table 1). Only one patient presented with stage III. At operation, however, 3 (10%) of the patients in clinical stage I had advanced disease. Two patients were in surgicopathological stage III and one patient in stage IV (Table 1). ESCC has a poor prognosis. Nine of the twenty-five patients (36%) in clinical stage I whose follow-up is recorded [8/20 (40%) patients in surgicopathological stage I] died within 36 months. Disease-free survival among the remaining patients ranged from 2 to 60 months when reported. Our three cases had locally advanced disease, all of them with infiltration to the serosa. In case 1 widespread metastases and in case 2 pelvic lymph node metastases were found. All cases died within a year, cases 1 and 3 of residual or recurrent disease and case 2 of complications of treatment. Hysterectomy with or without bilateral salpingo-oophorectomy was performed in all the accepted cases of ESCC. The benefit of pre- or postoperative irradiation has not been documented. Five of eight irradiated patients in surgicopathological stage I died of disease, compared with 2 of 11 nonirradiated patients. Recorded follow-up time was, however, very short. Chemotherapy was not employed in any of the published cases of ESCC. REFERENCES 1. Gebhard, C. Ueber die vom Oberlllchenepithel ausgehenden Carcinomformen des Uteruskorpers sowie tlber den Homkrebs des Cavum uteri, Z. Geburtsh. Perinaral. 24, l-8 (1892). 2. Flaischlen, N. Ueber den primaren Hornkrebs des Corpus Uteri, Z. Geburtsh. Perinafal. 32, 347-355 (1895). 3. Batchelor, F. C., and Doran, A. Primary squamous-celled epithelioma of the body of the uterus, Trans. Obsrer. Sot. 45, 374-377 (1903). 4. Norris, C. C. Primary squamous celled carcinoma of the body of the uterus. Amer. J. Obstet. Gynecol. 56, 787-793 (1907). 5. Spranger, H. Uber einen besonders bemerkenswerten Fall von doppeltem Primarcarcinom, Z. Krebsforsch. 20, 243-249 (1923). 6. Williamson, H., and Abercrombie, G. F. A case of inversion of the uterus caused by a squamous-celled carcinoma of the fundus, J. Obstet. Gynecol. Brit. Emp. 30, 643-646 (1923). 7. de Gery, C., and Perrot, M. A propos d’un cas d’tpithtlioma Malpighien du corps uterin, Ann. Anat. Pathol. (Paris) 9, 317-321 (1932). 8. Wahi, P. N., and Jain, R. L. Epidermoid carcinoma of the corpus uteri, Zndiun J. Med. Sci. 3, 417-420 (1949).
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9. Chu, F., LePow, H., and Godsick, W. Primary squamous-cell carcinoma of the corpus uteri, Arch. Pathol. 65, 13-17 (1958). 10. Peris, L. A., Jernstrom, P., and Bowers, P. A. Primary squamouscell carcinoma of the uterine corpus. Report of a case and review of the literature, Amer. J. Obstet. Gynecol. 75, 1019-1026 (1958). 11. Gillespie, C. F. Chronic inversion of the uterus with presenting epidermoid carcinoma. Report of a case, Obster. Gynecol. 20, 801804 (1962). 12. Mazzella, G. II carcinoma epidermoide dell’endometrio, Rnssegna ht. C/in. Ter. 43, 613-620 (1963). 13, Barnett, H. Squamous cell carcinoma of the body of the uterus, .I. C/in. Patho/. 18, 715-722 (1965). 14. Levine, S., and Sciorsci, E. F. Squamous cell carcinoma of the uterine corpus and its relation to pyometra, Cancer 19, 485-488 (1966). 15. Maheshwari, H. B., Madan, P., and Kumar, S. Primary squamous cell carcinoma of corpus uteri, (A case report) Indian J. Pathol. Bacterial. 10, 95-98 (1967). 16. Bellone, F. II carcinoma epidermoide primitive dell’endometrio. Descrizione di un case, Arch. Ostet. Ginecol. 73, 1086-1095 (1968). 17. Hopkin, I. D., Harlow, R. A., and Stevens, P. J. Squamous carcinoma of the body of the uterus, Brit. J. Cancer 24, 71-76 (1970). 18. White, A. J., Buchsbaum, H. J., and Macasaet. M. A. Primary squamous cell carcinoma of the endometrium, Obstet. Gynecol. 41, 912-919 (1973). 19. Menezer, J. Primary squamous cell carcinoma of the endometrium, Harefuah 89, 169-170 (1975). 20. Kay, S. Squamous-cell carcinoma of the endometrium, Amer. J. C/in. Pathol. 61, 264-269 (1974). 21. Seltzer, V. L., Klein, M., and Beckman, M. The occurrence of squamous cell metaplasia as a precursor of squamous cell carcinoma of the endometrium, Obstet. Gynecol. (Suppl.) 49, 34-37 (1977). 22. Taghinia, M. A., and Nasirai, F. Primary squamous cell carcinoma of the endometrium. Report of a case and review of the literature. Pahlawi Med. J. 8, 459-467 (1977). 23. Melin, J. R., Wanner, L., Schulz, D. M., and Cassel, E. E. Primary squamous cell carcinoma of the endometrium, Obstet. Gynecol. 53, 115-l I9 (1979).
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32. Fluhman, C. F. Squamous epithelium in the endometrium in benign and malignant conditions, Surg. Gynecol. Obstet. 46, 309-316 (1928). 33. Paulsen, H., and Taylor, C. International histological c/a&cation of tumors. No. 13. Histological typing of female genital tract rumors, No. 13, World Health Organization, Geneva (1975). 34. Baggish, M. S., and Woodruff, J. D. The occurrence of squamous epithelium in the endometrium, Obstet. Gynecol. Surv. 22, 69-115 (1967). 35. Histological typing of lung turnours, No. 1, 2nd ed., World Health Organization, Geneva (1981). im 36. Piering. Ueber einen Fall von atypischer Carcinombildung Uterus, Z. Heilkunde, Bd.8 (1887).