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An unusual polypoid lesion Part 2
524
KARIM AND RUSSELL
Pathology (2003), 35(6), December
An unusual polypoid lesion Part 2
EXPLANATION AND DIAGNOSIS: BENIGN METAPLASTIC PAPILLARY CHANGE IN AN ENDOMETRIAL POLYP Endometrial polyps are common and can exhibit a wide spectrum of morphological and cytological features, but rarely as bizarre as the present case. The endometrium is a particularly variable tissue changing its morphology with patient age and cyclical hormonal stimulation, as well as undergoing a variety of simple metaplastic changes. Any physiological or pathological appearance encountered in the endometrium may be seen within a polyp. Stromal elements of a polyp can also contribute to this morphological diversity. The polyps in this example have a combination of architectural complexity with cytological blandness. The immunophenotype is consistent with mu¨llerian differentiation. The basic architectural construct of endometrial epithelium is that of a straight non-branching tubular gland. Functional activity and hyperplasias may superficially alter the appearance of these glandular elements but do not engender the development of papillae—an appearance more typical of endocervical or endosalpingeal mucosa. Implied, therefore, in the development of such a papillary or villoglandular pattern is the superimposition of mu¨llerian metaplasia. Additionally, the diagnosis of hyperplasia can be problematic in endometrial polyps, due to the frequently irregular glandular pattern, imparting a more complex and crowded appearance.1 In view of the above and the strong association with metaplasia, we prefer the designation ‘metaplastic papillary change’ and consider it a benign process. In 2001, Lehman and Hart2 reported nine cases of localised papillary lesions devoid of malignant nuclear features, with fibrovascular cores and epithelial metaplasia. Post-menopausal bleeding was the most common symptom and six of the nine lesions were within endometrial polyps. All nine cases had varying combinations of epithelial metaplasia, most commonly endocervical, and all had uneventful outcomes. They divided the cases into simple and complex papillary hyperplasia based on the architectural complexity. The present case would fit the complex papillary hyperplasia described due to the florid papillary pattern with branching filiform folia replacing much of the polyps. However the four complex papillary hyperplasias described by Lehman and Hart2 also had mild nuclear atypia manifest as slight hyperchromasia and irregular nuclear borders not seen here. They also reported epithelial tufting and multilayering in the complex papillary hyperplasia, in contrast to the simple epithelium lining the papilla in the present case. In 1998, Hendrickson and Kempson3 proposed a classification of endometrial metaplasia into those whose architecture and cytology were not ‘worrisome’, and those
whose overall architectural pattern would be found in hyperplasia with atypia. The second group was termed ‘metaplastic hyperplasia’ and they postulated that these patients with metaplasia of complex, hence hyperplastic, glands probably represent a subset of those who are at increased risk of developing an adenocarcinoma. The most important consideration in the differential diagnosis is low-grade papillary adenocarcinoma. When the architectural papillary pattern is complex, some investigators regard them as well-differentiated adenocarcinomas.4 Longacre et al. proposed criteria to determine morphological features most predictive of myoinvasion.4 They found that papillary lesions composed of exophytic, coarse or fine papillae were significantly associated with myoinvasion and concluded that their presence in any amount was diagnostic of carcinoma independent of cytology. Lehman and Hart2 noted that certain leaf-like exophytic patterns were not deemed papillary, despite the presence of stromal cores and these were found to be associated with a very low risk of myoinvasion in the Longacre et al.4 study. The validity of diagnosing endometrial adenocarcinoma exclusively on the basis of finding a papillary architectural pattern without regard of the size of the lesion or degree of nuclear atypia has been questioned2, and the blandness of the present lesion would appear sufficient to rule out any likelihood of biological malignancy. Papillary serous carcinoma (PSC), the villoglandular variant of endometrioid adenocarcinoma, clear cell carcinoma and mucinous adenocarcinoma may all have papillary architectures. However, it is most classical of serous carcinoma.5 In the endometrium, PSC may be confined to polyps6,7, and is usually a high-grade cancer with markedly atypical nuclei, high nuclear/cytoplasmic ratio, numerous mitoses and a fine hierarchical papillary pattern.2,6 The epithelial cells tend to be small cuboidal rather than columnar.5 Although the papillae of the present polypoid lesion are fine, filiform and branching, they lack the hierarchical arborisation typical of PSC. Additionally, they lack the high-grade nuclei of the frankly malignant epithelial lining cells—the hallmark of PSC.5,7 The villoglandular variant of endometrioid carcinoma displays only mild cellular atypia, and may also be confined to one or more polyps. However, the papillary fronds are typically long, simple, and without significant branching.5,8 Papillary areas only compose a portion of the tumour in clear cell adenocarcinoma.5 Solid and tubulo-cystic areas with clear and ‘hobnail’ cells should also be present elsewhere.5 The tall columnar cells of mucinous carcinomas have different morphology from the majority of the epithelial cells in the present case. So-called papillary syncytial metaplasia (or surface papillary metaplasia) may be seen in polyps. In this condition there are syncytial to papillary aggregates of
TEST AND TEACH
small eosinophilic cuboidal to spindled epithelial cells.3,9 Fibrovascular cores and hence true papillae are absent.3,9,10 Papillary syncytial metaplasia is usually seen in pre-menopausal women associated with endometrial breakdown, and may be a morphological expression of active endometrial breakdown rather than a true metaplasia.3,9,10 Small papillary tumours resembling benign ovarian serous tumours may occur rarely in endometrium.11 The ovarian serous tumour epithelium most commonly resembles that of tubal mucosa.11 Some cells produce extracellular but not intracellular mucin, have a mucicarmine-positive glycocalyx and diastase-resistant PAS-positive apical cytoplasm; as was found in the two polyps.11 However the benign serous tumours tend to have a simple blunt papilla rather than the fine, filiform structures here.11,12,13 The finer papillary pattern of these two polyps would be more similar to proliferating serous tumours (i.e. of borderline malignancy) but lacks the cellular atypia of such lesions.11 Proliferating serous tumours are also characterised by epithelial stratification and tufting.12 Ciliated cells are most usually present and a range of cytological atypia is seen.13 Similarly, mu¨llerian adenofibromas can have papillary architectures but the epithelium penetrates in long clefts into the underlying prominent stroma, a feature lacking in the present lesions.14 The absence of stromal smooth muscle and cytological atypia excludes atypical polypoid adenomyoma as a differential diagnosis.14 The rarity of such polyps, as reported in the literature, precludes any definitive prediction of their clinical consequences. However, the very bland cytological appearance of the cells is reassuring and should be stressed and long-term follow-up recommended. The morphology of the remaining endometrium, atrophic in this case, may be of key importance.
Key words: endometrial polyp, papillary polyp, mu¨llerian epithelium, pathology.
525
Address for correspondence: Professor Peter Russell, Department of Anatomical Pathology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050 Australia. E-mail: [email protected]. gov.au
References
1. Anderson M, Robboy S, Russell P, Morse A. Endometritis, Metaplasias and Polyps. In: Robboy S, Anderson M, Russell P, editors. Pathology of the Female Reproductive Tract. London: Churchill Livingstone, 2002; 294–301. 2. Lehman MB, Hart WR. Simple and complex hyperplastic proliferations of the endometrium. American Journal of Surgical Pathology 2001; 25: 1347–54. 3. Hendrickson MR, Kempson RL. Endometrial epithelial metaplasias: proliferations frequently misdiagnosed as adenocarcinoma. American Journal of Surgical Pathology 1980; 4: 525–42. 4. Longacre TA, Chung MH, Jensen DN, Hendrickson MR. Proposed criteria for the diagnosis of well-differentiated endometrial carcinoma. American Journal of Surgical Pathology 1995; 19: 371–406. 5. Anderson M, Robboy S, Russell P, Morse A. Endometrial Carcinoma. In: Robboy S, Anderson M, Russell P, editors. Pathology of the Female Genital Tract. London: Churchill Livingstone, 2002; 334–52. 6. Lauchlan SC. Metaplasia and neoplasias of Mu¨llerian epithelium. Histopathology 1984; 8: 543–57. 7. Sherman ME, Bitterman P, Rosenshein NB, Delgado G, Kurman RJ. Uterine serous carcinoma. American Journal of Surgical Pathology 1992; 16: 600–10. 8. Rosai J. Female Reproductive System. In: Rosai J, editor. Ackerman’s Surgical Pathology. 8th ed. St Louis: Mosby, 1996; 1473–8. 9. Zaman SS, Mazur MT. Endometrial papillary syncytial change. American Journal of Clinical Pathology 1993; 99: 741–5. 10. Hendrickson M, Longacre T, Kempson. The Uterus. In: Sternberg S, editor. Diagnostic Surgical Pathology. 3rd ed. New York: Lippincott Williams and Wilkins, 1999; 2203–2305. 11. Seidman J, Russell P, Kurman R. Surface Epithelial Tumours of the Ovary. In: Kurman RJ, editor. Blaustein’s Pathology of the Female Genital Tract. 5th ed. New York: Springer-Verlag Inc, 2002; 812–31. 12. Russell P, Robboy S, Anderson M. Ovary: Epithelial/Stromal Tumours. In: Robboy S, Anderson M, Russell P, editors. Pathology of the Female Genital Tract. London: Churchill Livingstone, 2002; 539–55. 13. Young R, Clement P, Scully R(1999) The Ovary. In: Sternberg S, editor. Diagnostic Surgical Pathology. 3rd ed. New York: Lippincott Williams and Wilkins, 1999; 2322–8. 14. Silverberg SG, Kurman RJ. Endometrial Polyps and Hyperplasias. In: Tumours of the Uterine Corpus and Gestational Trophoblast Disease, Atlas of Tumour Pathology Fascicle 3; Washington DC: Armed Forces Institute of Pathology, 1992; 15–18.
KARIM AND RUSSELL
Pathology (2003), 35(6), December
An unusual polypoid lesion Part 2
EXPLANATION AND DIAGNOSIS: BENIGN METAPLASTIC PAPILLARY CHANGE IN AN ENDOMETRIAL POLYP Endometrial polyps are common and can exhibit a wide spectrum of morphological and cytological features, but rarely as bizarre as the present case. The endometrium is a particularly variable tissue changing its morphology with patient age and cyclical hormonal stimulation, as well as undergoing a variety of simple metaplastic changes. Any physiological or pathological appearance encountered in the endometrium may be seen within a polyp. Stromal elements of a polyp can also contribute to this morphological diversity. The polyps in this example have a combination of architectural complexity with cytological blandness. The immunophenotype is consistent with mu¨llerian differentiation. The basic architectural construct of endometrial epithelium is that of a straight non-branching tubular gland. Functional activity and hyperplasias may superficially alter the appearance of these glandular elements but do not engender the development of papillae—an appearance more typical of endocervical or endosalpingeal mucosa. Implied, therefore, in the development of such a papillary or villoglandular pattern is the superimposition of mu¨llerian metaplasia. Additionally, the diagnosis of hyperplasia can be problematic in endometrial polyps, due to the frequently irregular glandular pattern, imparting a more complex and crowded appearance.1 In view of the above and the strong association with metaplasia, we prefer the designation ‘metaplastic papillary change’ and consider it a benign process. In 2001, Lehman and Hart2 reported nine cases of localised papillary lesions devoid of malignant nuclear features, with fibrovascular cores and epithelial metaplasia. Post-menopausal bleeding was the most common symptom and six of the nine lesions were within endometrial polyps. All nine cases had varying combinations of epithelial metaplasia, most commonly endocervical, and all had uneventful outcomes. They divided the cases into simple and complex papillary hyperplasia based on the architectural complexity. The present case would fit the complex papillary hyperplasia described due to the florid papillary pattern with branching filiform folia replacing much of the polyps. However the four complex papillary hyperplasias described by Lehman and Hart2 also had mild nuclear atypia manifest as slight hyperchromasia and irregular nuclear borders not seen here. They also reported epithelial tufting and multilayering in the complex papillary hyperplasia, in contrast to the simple epithelium lining the papilla in the present case. In 1998, Hendrickson and Kempson3 proposed a classification of endometrial metaplasia into those whose architecture and cytology were not ‘worrisome’, and those
whose overall architectural pattern would be found in hyperplasia with atypia. The second group was termed ‘metaplastic hyperplasia’ and they postulated that these patients with metaplasia of complex, hence hyperplastic, glands probably represent a subset of those who are at increased risk of developing an adenocarcinoma. The most important consideration in the differential diagnosis is low-grade papillary adenocarcinoma. When the architectural papillary pattern is complex, some investigators regard them as well-differentiated adenocarcinomas.4 Longacre et al. proposed criteria to determine morphological features most predictive of myoinvasion.4 They found that papillary lesions composed of exophytic, coarse or fine papillae were significantly associated with myoinvasion and concluded that their presence in any amount was diagnostic of carcinoma independent of cytology. Lehman and Hart2 noted that certain leaf-like exophytic patterns were not deemed papillary, despite the presence of stromal cores and these were found to be associated with a very low risk of myoinvasion in the Longacre et al.4 study. The validity of diagnosing endometrial adenocarcinoma exclusively on the basis of finding a papillary architectural pattern without regard of the size of the lesion or degree of nuclear atypia has been questioned2, and the blandness of the present lesion would appear sufficient to rule out any likelihood of biological malignancy. Papillary serous carcinoma (PSC), the villoglandular variant of endometrioid adenocarcinoma, clear cell carcinoma and mucinous adenocarcinoma may all have papillary architectures. However, it is most classical of serous carcinoma.5 In the endometrium, PSC may be confined to polyps6,7, and is usually a high-grade cancer with markedly atypical nuclei, high nuclear/cytoplasmic ratio, numerous mitoses and a fine hierarchical papillary pattern.2,6 The epithelial cells tend to be small cuboidal rather than columnar.5 Although the papillae of the present polypoid lesion are fine, filiform and branching, they lack the hierarchical arborisation typical of PSC. Additionally, they lack the high-grade nuclei of the frankly malignant epithelial lining cells—the hallmark of PSC.5,7 The villoglandular variant of endometrioid carcinoma displays only mild cellular atypia, and may also be confined to one or more polyps. However, the papillary fronds are typically long, simple, and without significant branching.5,8 Papillary areas only compose a portion of the tumour in clear cell adenocarcinoma.5 Solid and tubulo-cystic areas with clear and ‘hobnail’ cells should also be present elsewhere.5 The tall columnar cells of mucinous carcinomas have different morphology from the majority of the epithelial cells in the present case. So-called papillary syncytial metaplasia (or surface papillary metaplasia) may be seen in polyps. In this condition there are syncytial to papillary aggregates of
TEST AND TEACH
small eosinophilic cuboidal to spindled epithelial cells.3,9 Fibrovascular cores and hence true papillae are absent.3,9,10 Papillary syncytial metaplasia is usually seen in pre-menopausal women associated with endometrial breakdown, and may be a morphological expression of active endometrial breakdown rather than a true metaplasia.3,9,10 Small papillary tumours resembling benign ovarian serous tumours may occur rarely in endometrium.11 The ovarian serous tumour epithelium most commonly resembles that of tubal mucosa.11 Some cells produce extracellular but not intracellular mucin, have a mucicarmine-positive glycocalyx and diastase-resistant PAS-positive apical cytoplasm; as was found in the two polyps.11 However the benign serous tumours tend to have a simple blunt papilla rather than the fine, filiform structures here.11,12,13 The finer papillary pattern of these two polyps would be more similar to proliferating serous tumours (i.e. of borderline malignancy) but lacks the cellular atypia of such lesions.11 Proliferating serous tumours are also characterised by epithelial stratification and tufting.12 Ciliated cells are most usually present and a range of cytological atypia is seen.13 Similarly, mu¨llerian adenofibromas can have papillary architectures but the epithelium penetrates in long clefts into the underlying prominent stroma, a feature lacking in the present lesions.14 The absence of stromal smooth muscle and cytological atypia excludes atypical polypoid adenomyoma as a differential diagnosis.14 The rarity of such polyps, as reported in the literature, precludes any definitive prediction of their clinical consequences. However, the very bland cytological appearance of the cells is reassuring and should be stressed and long-term follow-up recommended. The morphology of the remaining endometrium, atrophic in this case, may be of key importance.
Key words: endometrial polyp, papillary polyp, mu¨llerian epithelium, pathology.
525
Address for correspondence: Professor Peter Russell, Department of Anatomical Pathology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050 Australia. E-mail: [email protected]. gov.au
References
1. Anderson M, Robboy S, Russell P, Morse A. Endometritis, Metaplasias and Polyps. In: Robboy S, Anderson M, Russell P, editors. Pathology of the Female Reproductive Tract. London: Churchill Livingstone, 2002; 294–301. 2. Lehman MB, Hart WR. Simple and complex hyperplastic proliferations of the endometrium. American Journal of Surgical Pathology 2001; 25: 1347–54. 3. Hendrickson MR, Kempson RL. Endometrial epithelial metaplasias: proliferations frequently misdiagnosed as adenocarcinoma. American Journal of Surgical Pathology 1980; 4: 525–42. 4. Longacre TA, Chung MH, Jensen DN, Hendrickson MR. Proposed criteria for the diagnosis of well-differentiated endometrial carcinoma. American Journal of Surgical Pathology 1995; 19: 371–406. 5. Anderson M, Robboy S, Russell P, Morse A. Endometrial Carcinoma. In: Robboy S, Anderson M, Russell P, editors. Pathology of the Female Genital Tract. London: Churchill Livingstone, 2002; 334–52. 6. Lauchlan SC. Metaplasia and neoplasias of Mu¨llerian epithelium. Histopathology 1984; 8: 543–57. 7. Sherman ME, Bitterman P, Rosenshein NB, Delgado G, Kurman RJ. Uterine serous carcinoma. American Journal of Surgical Pathology 1992; 16: 600–10. 8. Rosai J. Female Reproductive System. In: Rosai J, editor. Ackerman’s Surgical Pathology. 8th ed. St Louis: Mosby, 1996; 1473–8. 9. Zaman SS, Mazur MT. Endometrial papillary syncytial change. American Journal of Clinical Pathology 1993; 99: 741–5. 10. Hendrickson M, Longacre T, Kempson. The Uterus. In: Sternberg S, editor. Diagnostic Surgical Pathology. 3rd ed. New York: Lippincott Williams and Wilkins, 1999; 2203–2305. 11. Seidman J, Russell P, Kurman R. Surface Epithelial Tumours of the Ovary. In: Kurman RJ, editor. Blaustein’s Pathology of the Female Genital Tract. 5th ed. New York: Springer-Verlag Inc, 2002; 812–31. 12. Russell P, Robboy S, Anderson M. Ovary: Epithelial/Stromal Tumours. In: Robboy S, Anderson M, Russell P, editors. Pathology of the Female Genital Tract. London: Churchill Livingstone, 2002; 539–55. 13. Young R, Clement P, Scully R(1999) The Ovary. In: Sternberg S, editor. Diagnostic Surgical Pathology. 3rd ed. New York: Lippincott Williams and Wilkins, 1999; 2322–8. 14. Silverberg SG, Kurman RJ. Endometrial Polyps and Hyperplasias. In: Tumours of the Uterine Corpus and Gestational Trophoblast Disease, Atlas of Tumour Pathology Fascicle 3; Washington DC: Armed Forces Institute of Pathology, 1992; 15–18.