Vol. 67, No. 6
447
Adenomatoid Tumor of the Uterus Report of Two Cases AANTHONY IKPECHUKWU AGBATA. M.D., Residlent in
PatImnlogv,
a111(
JOSEPH KOVI, M.D., F.R.C.Path., Professor of Pathology, How'ar(d University College of Vledicine, WaVshing,toni, D.C.
GOLDEN and Ash' suggested the term "'adenomatoid tumor" in 1945 for certain peculiar neoplasms of the genital tract of unknown histogenesis. A wide ranging variety of terms, including lymphangioma, mesothelioma, angiomatoid tumor, adenomyoma etc., have been used to describe this neoplasm.2'3 Histogenetically, endothelial, mullerian, mesothelial and mesonephric origins have been proposed.36 The majority of reported cases have occurred in male patients and commonly involved the lower pole of the epididymis. In the female, adenomatoid tumors have been described in the fallopian tube and in a few instances in the uterus and ovary.2'4'7 It is important that the surgeon and the pathologist recognize the existence of this tumor because the histological pattern is sometimes bizarre and the lesion could be misdiagnosed as malignant. Jones and Donovan8 reported a case where the frozen section was diagnosed as carcinoma. This paper reports the clinical and pathological findings (including histochemical investigations) in two recent cases of adenomatoid tumor of the uterus. CASE REPORTS
C(ise No. 1. A 33-year-old black woman, gravida IV, para IV, was admitted for tubal ligation. The laboratory data, including SMA 12/60, urine analysis, chest x-ray, pap smear and blood count, were within normal limits. An Irving tubal ligation was performed. At surgery, a small subserosal nodule, measuring 0.5 cm in diameter, was found at the cornual end in the left aspect of the uterus, and removed.
The nodule presented a "bizarre" microscopic pattern that was variously diagnosed as myoblastoma or metastatic adenocarcinoma. Caise No. 2. A 36-year-old black female, gravida V, para III, presented with abdominal pain, and menorrhagia of several years duration. Review of the urinary and gastro-intestinal systems was negative. The blood pressure was 140/90. The cervix was conical, firm and clean. The uterus was movable, somewhat enlarged, and slightly tender. In the left adnexa, there was a tender cystic mass. A presumptive diagnosis of uterine fibroids and left ovarian cysts was made. The laboratory data, including SMA 12/60 coniplete blood count, urine analysis, serologic test for syphilis and fasting blood sugar, were within normal range. A laparatomy was done. The uterus was found to be grossly enlarged and irregular. The left fallopian tube appeared normal, but the left ovary was enlarged and cystic. The right ovary and fallopian tube were absent. Total abdominal hysterectomy, left salpingo-oophorectomy and posterior repair were
performed. A firm well circumscribed white tumor measuring 3.5x3.0 x2.5 cm. was located subserosally in the corpus. This was diagnosed microscopically as an adenomatoid tumor. Microscopic findings. The subserosal nodules revealed identical histopathologic changes in both cases. The tumor showed epithelial-like cells which formed cords and nests, and infiltrated the smooth musculature of the uterus. The cells were large, polygonal and had small vesicular nuclei. Mitotic activity, pleomorphism, and nuclear hyperchromatism were notably absent (Fig. I Left). Many small cystic spaces lined by low cuboidal cells were present. Sometimes the lining cells were flattened. The cystic spaces occasionally contained a fibrillar mucin-like material (Fig. I Middle). In other areas, the tumor cells exhibited distinct vacuolization. The vacuoles appeared to contain a pale blue mucinous material with the routine hematoxylin and eosin stain (Fig. I Right). A pseudocapsule, composed of compressed smooth muscle fibers, was present. Occasional small cystic spaces similar to the ones already described were noted in the pseudocapsule. The faint, blue fibrillar material in the cytoplasmic vacuoles of the tumor cells and in the small cystic spaces, gave a negative reaction with Periodic Acid-Schiff (PAS), with and without diastase digestion. No mucin-like material could be demonstrated in the tumor cells, or in the cystic spaces with mucicarmine. Alcian blue gave a strong positive reaction in
448
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
the cytoplasmic vacuoles of the tumor cells and in the lumina of the cystic spaces. Stromal reactivity was also noted in the vicinity of the nests and cords of tumor cells. In those sections pretreated with hyaluronidase, partial digestion of the alcian blue positive material was evident. The colloidal iron reaction, done according to the method of Broth, Bullock and Morrow,3 was positive in the tumor cells.
Fig. 1. Case I (LEFT). Photomicrograph of subserosal nodule of uterus showing cords of large, polygonal epitheliallike cells infiltrating the smooth muscle. Case 1 (MIDDLE). Small cystic spaces lined by low cuboidal cells. Some of the lumina contain secreted material. Case 2 (RIGHT). Many of the large, polygonal cells show vacuolization. Diffuse sprinkling of lymphocytes is seen in the stroma (H & E x 200). DISCUSSION
A neoplasm, probably adenomatoid tumor, was first described by Sakaguchi in 1916.9 The possibility that the pathologist, not familiar with this lesion, may diagnose this lesion as adenocarcinoma on the basis of its histologic appearance, is a real one. The major controversy about adenomatoid tumors is the question of origin of the neoplastic cells. Taxy, et al.4 and Siegler and Aristazobal5 described three patterns of this tumor, plexiform, tubular and canalicular. A mixture of these patterns is often seen in adenomatoid tumor, but not in adenocarcinoma.2'4 Also the complete absence of mitotic activity, cellular and nuclear pleomorphism should help to distinguish this tumor from adenocarcinoma. 2'7 In this context, it is important to demonstrate the presence of acid mucopolysaccharides (AMPS) with special stains such as colloidal iron, alcian blue or toluidine blue, with and without hyaluronidase predigestion.24 Broth et al.3 pointed out that epithelial acid mucopolysaccharides are not hydrolyzable with hyaluronidase in contradistinction to mesothelial and adenomatoid tumor acid mucopolysaccharides. According to Jackson,6 the possible
NOVEMBER, 1975
sources of origin of adenomatoid tumor are endothelial, mesothelial cells, or mullerian, or mesonephric remnants. A number of authors have ascribed the epithelial-like character of adenomatoid tumors to endothelial cell proliferation from lymphatics and blood vessels.10 12 However, intracytoplasmic vacuoles are not noted in endothelial cells.2 Many authors are of the opinion that the tumor cells are of mesothelial origin.3'4'13 Young and Taylor2 were able to demonstrate a continuity between the mesothelium of the tubal serosa and cells lining the cystic spaces of the adenomatoid tumor. The frequent location of this tumor just beneath a serosal surface would suggest a mesothelial origin.2'4'8 Adenomatoid tumors in the female are usually asymptomatic and are incidental findings at hysterectomy and or salpingo-oophorectomy for other reasons. 1'2'7 In the uterus, they are usually subserosal and located near the cornual region.2'4'5 Multiple adenomatoid tumors of the tunica vaginalis have been reported by Malament and Ries.14 Follow-up information is now available in a number of cases.2'13 In no instances was there a recurrence or metastases reported. SUMMARY
Two patients with an adenomatoid tumor of the uterus are described. In both patients, the tumor was an incidental finding at surgery, and was located near the cornual region of the uterus. The tumor cells secreted hyaluronidase-sensitive acid mucopolysaccharides. The importance of this rare lesion is that it may be confused histologically with a metastatic adenocarcinoma. LITERATURE CITED
1. GOLDEN, A. and J. E. ASH. Adenomatoid Tumors of the Genital Tract. Am. J. Path., 21:63, 1945. 2. YOUNGS, L. A. and H. B. TAYLOR. Adenomatoid Tumors of the Uterus and Fallopian Tube. Am. J. Clin. Path., 48:537, 1967. 3. BROTH, G. and W. K. BULLOCK and J. MORROW. Epididymal Tumors - I. Report of
Vol. 67, No. 6
4.
5. 6. 7.
8.
Adenomatoid Tumor of the Uterus
449
1965. 9. SAKAGUCHI, Y. Uber das Adenomyom des Nebenhodens. Frankfurt. Ztschr. f. Path., 18:379, 1916. 10. SANES, S. and R. WARNER. Primary Lymphangioma of the Fallopian Tube. Am. J. Obstet. & Gynecol., 37:316, 1939. 11. SALM, R. Cavernous Lymphangioma of the Uterus. Am. J. Obstet. & Gynecol., 80:365, 1960. 12. MOREHEAD, R. P. Angiomatoid Formations in the Genital Organs with and without Tumor Formation. Arch. Path., 42:56, 1946. 13. GLANTZ, G. M. Adenomatoid Tumors of the Epididymis: A Review of five New Cases, including a Case Report associated with Hydrocele. J. Urol., 95:227, 1966. 14. MALAMENT, M. and W. S. RIES. Multiple Adenomatoid Tumors of the Tunica Vaginalis, J. Urol., 92:210, 1964.
15 new Cases including Review of Literature. 2. Histochemical Study of the so-called Adenomatoid Tumor. J. UROL., 100:530, 1968. TAXY, J. B. and H. BATTIFORA and R. OYASU. Adenomatoid Tumors: A light Microscopic, Histochemical and Ultrastructural Study. Cancer, 34:306, 1974. SIEGLER, A. M. and M. ARISTAZOBAL. Mesothelioma of the Uterus: Report of a Case. Obstet. & Gynecol., 18:498, 1961. JACKSON, J. R. The Histogenesis of the Adenomatoid Tumor of the Genital Tract. Cancer, 11:377, 1958. JABLOKOW, V. R. and J. JAGATIC and M. E. RUBRITZ. Adenomatoid Tumors of the Genital Tract - Report of 12 Cases and Review of the Literature. J. Urol., 95:573, 1966. JONES, E. G. and A. J. DONOVAN. Adenomatoid Tumor of the Ovary Versus Mesothelial Reaction. Am. J. Obstet. & Gynecol., 92:694,
p (Brooks, from p. 482)
He has long been interested in the relationship between cancer and the ingestion of foods grown under stimulation of strong fertilizers. Darwin became a scientific immortal through synthesis of ideas developed from what he saw on one voyage on the Beagle. Dr. Brooks has now seen much at home and abroad. For quiet evaluations he likes to repair to his 35 foot Chris Craft cruiser on nearby Lake Kentucky, on which he is the skipper and not the "secretary" of Noronic days. Apparently love of the water has never left him for after receiving the General Practitioners Award at the Miami Beach Convention, he took his entire family of 10 on a long Caribbean cruise. In 1929, Dr. Brooks was appointed by the Governor of Kentucky to the staff of Western State Hospital, a mental institution, where he worked in psychiatry for four years and then went into private practice. In 1944, he built and opened the Brooks Memorial Hospital, a private 30 bed institution, in memory of his parents. In 1962, Dr. Brooks was elected to the Hopkinsville Board of Education on which he served for 11 years.
He is a member of the Pennyrile Medical Association, the Kentucky Medical Association, the NMA and the AMA, as well as of the Kentucky Thoracic Society. He serves on the Boards of Directors of the Pennyrile Area Health and Education System and the Mammoth Life and Accident Insurance Company. He' is also a member of the Hopkinsville and Christian County Chamber of Commerce, the Kentucky Human Relations Commission, Allied Organization for Civil Rights in KentVcky and he served on his local Selective Service Board. A life member of the NAACP, Dr. Brooks is a lay reader and vestryman in the local Grace Episcopal Church. He belongs to the Alpha Pi Alpha and Sigma Pi Phi fraternities. During his internship, Dr. Brooks married Miss Ethel Cowan of Washington, D.C. They have two sons, Philip C. Brooks, Jr. and Cowan H. Son Philip Jr. has two daughters, one attending Georgia Tech in engineering, and Cowan has two sons in secondary schools. W. MONTAGUE COBB, M.D.
447
Adenomatoid Tumor of the Uterus Report of Two Cases AANTHONY IKPECHUKWU AGBATA. M.D., Residlent in
PatImnlogv,
a111(
JOSEPH KOVI, M.D., F.R.C.Path., Professor of Pathology, How'ar(d University College of Vledicine, WaVshing,toni, D.C.
GOLDEN and Ash' suggested the term "'adenomatoid tumor" in 1945 for certain peculiar neoplasms of the genital tract of unknown histogenesis. A wide ranging variety of terms, including lymphangioma, mesothelioma, angiomatoid tumor, adenomyoma etc., have been used to describe this neoplasm.2'3 Histogenetically, endothelial, mullerian, mesothelial and mesonephric origins have been proposed.36 The majority of reported cases have occurred in male patients and commonly involved the lower pole of the epididymis. In the female, adenomatoid tumors have been described in the fallopian tube and in a few instances in the uterus and ovary.2'4'7 It is important that the surgeon and the pathologist recognize the existence of this tumor because the histological pattern is sometimes bizarre and the lesion could be misdiagnosed as malignant. Jones and Donovan8 reported a case where the frozen section was diagnosed as carcinoma. This paper reports the clinical and pathological findings (including histochemical investigations) in two recent cases of adenomatoid tumor of the uterus. CASE REPORTS
C(ise No. 1. A 33-year-old black woman, gravida IV, para IV, was admitted for tubal ligation. The laboratory data, including SMA 12/60, urine analysis, chest x-ray, pap smear and blood count, were within normal limits. An Irving tubal ligation was performed. At surgery, a small subserosal nodule, measuring 0.5 cm in diameter, was found at the cornual end in the left aspect of the uterus, and removed.
The nodule presented a "bizarre" microscopic pattern that was variously diagnosed as myoblastoma or metastatic adenocarcinoma. Caise No. 2. A 36-year-old black female, gravida V, para III, presented with abdominal pain, and menorrhagia of several years duration. Review of the urinary and gastro-intestinal systems was negative. The blood pressure was 140/90. The cervix was conical, firm and clean. The uterus was movable, somewhat enlarged, and slightly tender. In the left adnexa, there was a tender cystic mass. A presumptive diagnosis of uterine fibroids and left ovarian cysts was made. The laboratory data, including SMA 12/60 coniplete blood count, urine analysis, serologic test for syphilis and fasting blood sugar, were within normal range. A laparatomy was done. The uterus was found to be grossly enlarged and irregular. The left fallopian tube appeared normal, but the left ovary was enlarged and cystic. The right ovary and fallopian tube were absent. Total abdominal hysterectomy, left salpingo-oophorectomy and posterior repair were
performed. A firm well circumscribed white tumor measuring 3.5x3.0 x2.5 cm. was located subserosally in the corpus. This was diagnosed microscopically as an adenomatoid tumor. Microscopic findings. The subserosal nodules revealed identical histopathologic changes in both cases. The tumor showed epithelial-like cells which formed cords and nests, and infiltrated the smooth musculature of the uterus. The cells were large, polygonal and had small vesicular nuclei. Mitotic activity, pleomorphism, and nuclear hyperchromatism were notably absent (Fig. I Left). Many small cystic spaces lined by low cuboidal cells were present. Sometimes the lining cells were flattened. The cystic spaces occasionally contained a fibrillar mucin-like material (Fig. I Middle). In other areas, the tumor cells exhibited distinct vacuolization. The vacuoles appeared to contain a pale blue mucinous material with the routine hematoxylin and eosin stain (Fig. I Right). A pseudocapsule, composed of compressed smooth muscle fibers, was present. Occasional small cystic spaces similar to the ones already described were noted in the pseudocapsule. The faint, blue fibrillar material in the cytoplasmic vacuoles of the tumor cells and in the small cystic spaces, gave a negative reaction with Periodic Acid-Schiff (PAS), with and without diastase digestion. No mucin-like material could be demonstrated in the tumor cells, or in the cystic spaces with mucicarmine. Alcian blue gave a strong positive reaction in
448
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
the cytoplasmic vacuoles of the tumor cells and in the lumina of the cystic spaces. Stromal reactivity was also noted in the vicinity of the nests and cords of tumor cells. In those sections pretreated with hyaluronidase, partial digestion of the alcian blue positive material was evident. The colloidal iron reaction, done according to the method of Broth, Bullock and Morrow,3 was positive in the tumor cells.
Fig. 1. Case I (LEFT). Photomicrograph of subserosal nodule of uterus showing cords of large, polygonal epitheliallike cells infiltrating the smooth muscle. Case 1 (MIDDLE). Small cystic spaces lined by low cuboidal cells. Some of the lumina contain secreted material. Case 2 (RIGHT). Many of the large, polygonal cells show vacuolization. Diffuse sprinkling of lymphocytes is seen in the stroma (H & E x 200). DISCUSSION
A neoplasm, probably adenomatoid tumor, was first described by Sakaguchi in 1916.9 The possibility that the pathologist, not familiar with this lesion, may diagnose this lesion as adenocarcinoma on the basis of its histologic appearance, is a real one. The major controversy about adenomatoid tumors is the question of origin of the neoplastic cells. Taxy, et al.4 and Siegler and Aristazobal5 described three patterns of this tumor, plexiform, tubular and canalicular. A mixture of these patterns is often seen in adenomatoid tumor, but not in adenocarcinoma.2'4 Also the complete absence of mitotic activity, cellular and nuclear pleomorphism should help to distinguish this tumor from adenocarcinoma. 2'7 In this context, it is important to demonstrate the presence of acid mucopolysaccharides (AMPS) with special stains such as colloidal iron, alcian blue or toluidine blue, with and without hyaluronidase predigestion.24 Broth et al.3 pointed out that epithelial acid mucopolysaccharides are not hydrolyzable with hyaluronidase in contradistinction to mesothelial and adenomatoid tumor acid mucopolysaccharides. According to Jackson,6 the possible
NOVEMBER, 1975
sources of origin of adenomatoid tumor are endothelial, mesothelial cells, or mullerian, or mesonephric remnants. A number of authors have ascribed the epithelial-like character of adenomatoid tumors to endothelial cell proliferation from lymphatics and blood vessels.10 12 However, intracytoplasmic vacuoles are not noted in endothelial cells.2 Many authors are of the opinion that the tumor cells are of mesothelial origin.3'4'13 Young and Taylor2 were able to demonstrate a continuity between the mesothelium of the tubal serosa and cells lining the cystic spaces of the adenomatoid tumor. The frequent location of this tumor just beneath a serosal surface would suggest a mesothelial origin.2'4'8 Adenomatoid tumors in the female are usually asymptomatic and are incidental findings at hysterectomy and or salpingo-oophorectomy for other reasons. 1'2'7 In the uterus, they are usually subserosal and located near the cornual region.2'4'5 Multiple adenomatoid tumors of the tunica vaginalis have been reported by Malament and Ries.14 Follow-up information is now available in a number of cases.2'13 In no instances was there a recurrence or metastases reported. SUMMARY
Two patients with an adenomatoid tumor of the uterus are described. In both patients, the tumor was an incidental finding at surgery, and was located near the cornual region of the uterus. The tumor cells secreted hyaluronidase-sensitive acid mucopolysaccharides. The importance of this rare lesion is that it may be confused histologically with a metastatic adenocarcinoma. LITERATURE CITED
1. GOLDEN, A. and J. E. ASH. Adenomatoid Tumors of the Genital Tract. Am. J. Path., 21:63, 1945. 2. YOUNGS, L. A. and H. B. TAYLOR. Adenomatoid Tumors of the Uterus and Fallopian Tube. Am. J. Clin. Path., 48:537, 1967. 3. BROTH, G. and W. K. BULLOCK and J. MORROW. Epididymal Tumors - I. Report of
Vol. 67, No. 6
4.
5. 6. 7.
8.
Adenomatoid Tumor of the Uterus
449
1965. 9. SAKAGUCHI, Y. Uber das Adenomyom des Nebenhodens. Frankfurt. Ztschr. f. Path., 18:379, 1916. 10. SANES, S. and R. WARNER. Primary Lymphangioma of the Fallopian Tube. Am. J. Obstet. & Gynecol., 37:316, 1939. 11. SALM, R. Cavernous Lymphangioma of the Uterus. Am. J. Obstet. & Gynecol., 80:365, 1960. 12. MOREHEAD, R. P. Angiomatoid Formations in the Genital Organs with and without Tumor Formation. Arch. Path., 42:56, 1946. 13. GLANTZ, G. M. Adenomatoid Tumors of the Epididymis: A Review of five New Cases, including a Case Report associated with Hydrocele. J. Urol., 95:227, 1966. 14. MALAMENT, M. and W. S. RIES. Multiple Adenomatoid Tumors of the Tunica Vaginalis, J. Urol., 92:210, 1964.
15 new Cases including Review of Literature. 2. Histochemical Study of the so-called Adenomatoid Tumor. J. UROL., 100:530, 1968. TAXY, J. B. and H. BATTIFORA and R. OYASU. Adenomatoid Tumors: A light Microscopic, Histochemical and Ultrastructural Study. Cancer, 34:306, 1974. SIEGLER, A. M. and M. ARISTAZOBAL. Mesothelioma of the Uterus: Report of a Case. Obstet. & Gynecol., 18:498, 1961. JACKSON, J. R. The Histogenesis of the Adenomatoid Tumor of the Genital Tract. Cancer, 11:377, 1958. JABLOKOW, V. R. and J. JAGATIC and M. E. RUBRITZ. Adenomatoid Tumors of the Genital Tract - Report of 12 Cases and Review of the Literature. J. Urol., 95:573, 1966. JONES, E. G. and A. J. DONOVAN. Adenomatoid Tumor of the Ovary Versus Mesothelial Reaction. Am. J. Obstet. & Gynecol., 92:694,
p (Brooks, from p. 482)
He has long been interested in the relationship between cancer and the ingestion of foods grown under stimulation of strong fertilizers. Darwin became a scientific immortal through synthesis of ideas developed from what he saw on one voyage on the Beagle. Dr. Brooks has now seen much at home and abroad. For quiet evaluations he likes to repair to his 35 foot Chris Craft cruiser on nearby Lake Kentucky, on which he is the skipper and not the "secretary" of Noronic days. Apparently love of the water has never left him for after receiving the General Practitioners Award at the Miami Beach Convention, he took his entire family of 10 on a long Caribbean cruise. In 1929, Dr. Brooks was appointed by the Governor of Kentucky to the staff of Western State Hospital, a mental institution, where he worked in psychiatry for four years and then went into private practice. In 1944, he built and opened the Brooks Memorial Hospital, a private 30 bed institution, in memory of his parents. In 1962, Dr. Brooks was elected to the Hopkinsville Board of Education on which he served for 11 years.
He is a member of the Pennyrile Medical Association, the Kentucky Medical Association, the NMA and the AMA, as well as of the Kentucky Thoracic Society. He serves on the Boards of Directors of the Pennyrile Area Health and Education System and the Mammoth Life and Accident Insurance Company. He' is also a member of the Hopkinsville and Christian County Chamber of Commerce, the Kentucky Human Relations Commission, Allied Organization for Civil Rights in KentVcky and he served on his local Selective Service Board. A life member of the NAACP, Dr. Brooks is a lay reader and vestryman in the local Grace Episcopal Church. He belongs to the Alpha Pi Alpha and Sigma Pi Phi fraternities. During his internship, Dr. Brooks married Miss Ethel Cowan of Washington, D.C. They have two sons, Philip C. Brooks, Jr. and Cowan H. Son Philip Jr. has two daughters, one attending Georgia Tech in engineering, and Cowan has two sons in secondary schools. W. MONTAGUE COBB, M.D.
