International Journal of Gynecological Pathology 33:100–104, Lippincott Williams & Wilkins, Baltimore r 2013 International Society of Gynecological Pathologists
Case Report
Cystic Fibrosis Involving the Cervix, Mimicking a Well-differentiated Adenocarcinoma: A Case Report Rebecca A. Previs, M.D., James M. Edwards, M.D., Angeles A. Secord, M.D., Marisa R. Nucci, M.D., Rex C. Bentley, M.D., and Allison H. S. Hall, M.D.
Summary: We describe clinicopathologic and immunohistochemical features of an unusual case of cystic fibrosis manifesting in the cervix as a mass lesion, mimicking cervical adenocarcinoma. A 24-year-old nulligravida with cystic fibrosis developed heavy postcoital vaginal bleeding 4 months after starting oral contraceptives and was found to have a cervical mass. She underwent a loop electrosurgical excision of the mass, and microscopic examination revealed a florid endocervical proliferation, extending to the margins. This lesion was initially interpreted as an invasive, welldifferentiated endocervical adenocarcinoma. However, on subsequent review, the lesion was found to have a low rate of proliferation, no evidence of an infiltrative growth pattern, and abundant acute inflammation. Given these findings and the absence of any residual endocervical lesion on a subsequent cold knife conization, we determined that this was a benign, likely reactive, lesion. This case, together with previous studies, suggests that women with cystic fibrosis can develop proliferative endocervical lesions and that oral contraceptives may contribute to their development. Key Words: Cervical carcinoma—Cystic fibrosis—Endocervical hyperplasia—Oral contraceptives.
endocervical proliferation that was initially interpreted as a malignant lesion.
Cystic fibrosis (CF) is the most common lifethreatening genetic disease in the United States. Changes in the respiratory tract, gastrointestinal tract, and male reproductive tract related to CF have been well described. In contrast, the effects of CF on the female reproductive tract are less well understood. Here, we present the case of a young woman with CF who developed a benign, but florid
CASE REPORT A 24-year-old nulligravida with a past medical history significant for CF, bilateral lung transplantation, insulin-dependent diabetes mellitus, chronic pancreatitis, chronic sinusitis, and gastroparesis presented to her primary gynecologist with a 4-month history of postcoital bleeding. She had normal pap smears in the preceding 3 years and had received the Gardasil vaccine at the age of 21. Before her presentation, she had been amenorrheic for over 1½ years after her transplant. She started on microgestin for contraception. She resumed normal menses after 4 months and concomitantly developed heavy postcoital spotting. Evaluation began with pelvic ultrasound, which revealed a normal-sized uterus with a 6.8-mm endometrial stripe and a cervical mass
From the Department of Obstetrics and Gynecology (A.A.S.), Division of Gynecologic Oncology, Duke Cancer Institute; Departments of Obstetrics and Gynecology (R.A.P., J.M.E.); Pathology (R.C.B., A.H.S.H.), Duke University Medical Center, Durham, North Carolina; and Department of Pathology (M.R.N.), Division of Women’s and Perinatal Pathology, Brigham and Women’s Hospital, Boston, Massachusetts. The authors declare no conflict of interest. Address correspondence and reprint requests to Rebecca A. Previs, MD, Department of Obstetrics and Gynecology, Duke University Medical Center, P.O. Box 3616, Durham, NC 27710. E-mail: [email protected].
DOI: 10.1097/PGP.0b013e318278b832
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CYSTIC FIBROSIS INVOLVING THE CERVIX described as a 3-cm friable, ectropion on the posterior lip of the cervix. A biopsy of the cervical mass was reported to show mild dysplasia. Of note, she discontinued her oral contraceptives at this time. A loop electrosurgical excision procedure was performed. The cervical excision specimen was reported to have a 2.5-cm papillary lesion on the mucosal surface. The stromal margin and the cut surfaces of the specimen were described as diffusely green-gray and mucinous. Microscopic examination revealed a proliferation of large, dilated mucinous glands with prominent acute inflammation (Fig. 1). The epithelium was focally hyperplasic, with papillary and microcystic growth patterns. Mitotic figures were very rare, and there was no significant cytologic atypia. The dilated glands extended 0.7 cm into the cervical stroma, involving the surgical margins. The glandular proliferation showed moderate to strong staining for CEA, focal, weak staining for p16 and p53, and showed a modest
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rate of proliferation by Ki-67 staining, which was positive in 10% to 20% of glandular cells (Fig. 2). The pathology results were initially interpreted as an invasive, well-differentiated endocervical adenocarcinoma. Her postoperative physical examination was significant for multiple scattered papules around the clitoral hood and perineum consistent with condylomatous and dysplastic changes. There were no visible lesions on the cervix or vagina. Bimanual examination confirmed a small, mobile uterus with no cervical nodularity. Positron emission tomography/computed tomography showed no cervical mass or hypermetabolic activity in the cervical region, and no evidence of metastasis. The slides from the patient’s original cervical excision were reviewed and immunohistochemical stainings were performed. Given the lack of significant cytologic atypia, the low rate of proliferation,
FIG. 1. Endocervical proliferation with dilated glands extending deep into the endocervical stroma (A, 20 ). The epithelium has microcystic and papillary growth patterns and there is prominent acute inflammation (B, 100 ). The nuclei are regular with no significant cytologic atypia (C, D, 400 ).
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FIG. 2. An immunohistochemical stain for Ki-67 shows a low rate of proliferation in the endocervical epithelium (A, 200 ). There is moderate to strong expression of CEA (B, 200 ), minimal expression of p16 (C, 200 ), and focal, weak expression of p53 (D, 200 ).
the absence of a truly infiltrative growth pattern, and the presence of abundant acute inflammation, we interpreted the lesion as a reactive process rather than a malignancy. Because the morphologic findings are similar to the glandular dilation and hyperplasia seen in other organ systems affected by CF, we felt that this could be a CF-related lesion. The specimen was sent for an additional outside consultation with concordant results. Because the proliferation extended to the loop electrosurgical excision procedure specimen margins, a cold knife conization was performed to further evaluate the lesion. Colposcopy of the vagina, cervix, and vulva and vulvar biopsies was also performed, as was a laparoscopic bilateral salpingectomy, at the patient’s request. Colposcopy of the cervix revealed acetowhite changes involving all 4 quadrants, but no evidence of abnormal vasculature. No vaginal lesions were appreciated. Vulvar colposcopy showed white leukoplakia involving the right labium minus and Int J Gynecol Pathol Vol. 33, No. 1, January 2014
upper part of the right labium majus. Small punctuate lesions were visible bilaterally. Representative biopsies were performed. On laparoscopic survey, the abdominal and pelvic anatomy appeared normal except for 2 small tracts between the stomach and jejunum to the abdominal wall, consistent with prior feeding tubes. The cervical conization specimen had no grossly apparent lesions. Microscopic examination revealed low-grade dysplasia (CIN-1) of the ectocervical epithelium, with prominent human papillomavirus cytopathic effect. The endocervical glands were unremarkable, with no residual hyperplasia. The endocervical epithelium was negative for p16 and showed a low rate of proliferation by Ki-67 staining (positive in 10%–20% of glandular cells). Vulvar biopsies performed at the same time also showed lowgrade dysplasia (VIN-1). Given the bland appearance of the endocervical proliferation in the loop electrosurgical excision procedure specimen and the absence
CYSTIC FIBROSIS INVOLVING THE CERVIX of any residual abnormality in the cold knife conization, we feel that this lesion is best described as a benign hyperplasia of the endocervical glands. DISCUSSION This case highlights effects of CF on the cervical epithelium that can mimic a well-differentiated invasive cervical cancer. Histologic abnormalities of the cervix associated with CF have received relatively little attention. However, it is known that women with CF have abnormally thick, dehydrated cervical mucus, which may contribute to infertility and hypofertility in some patients (1–6). In one of the few studies that addresses cervical pathology in patients with CF, Oppenheimer and Esterly (7) evaluated the female genital tract of 36 girls with CF, aged 4 days to 15 years at the time of autopsy. They found increased extracellular and intracellular mucin in the endocervical glands of all newborns and approximately half of older children with CF. Only 2 of these patients were peripubescent. This same group reported a single case of a young woman with CF who was found to have a benign endocervical polyp characterized by dilated glands and mucin-filled cysts (8). In addition, Dooley et al. (9) described three cases of young women with CF who developed inflammatory cervical polyps while on oral contraceptives. The women ranged in age from 22 to 26 and developed the cervical polyps between 2 months and 1 year after initiation of oral contraceptive therapy. On histologic examination, the polyps showed endocervical glandular proliferation and prominent inflammatory infiltrates consisting of neutrophils, plasma cells, and lymphocytes. All of the lesions regressed after oral contraceptives were discontinued. The findings in this case series are particularly interesting in light of the case presented here. The patient in the current report is also of 22 years old and developed an endocervical lesion with hyperplastic endocervical glands and conspicuous acute inflammation within a year of starting oral contraceptive therapy. There are several lines of evidence to suggest that this patient’s lesion could be related to her history of CF. Women with CF have abnormal, very viscous mucus, which could contribute to the marked glandular dilation observed in this case (1,2,6). Also, CF patients are known to develop similar hyperplastic lesions of mucous glands in the gall bladder, salivary gland, gastrointestinal tract, and respiratory tract (10).
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There is also evidence to support the idea that oral contraceptives could have contributed to the development of this lesion. Previous studies have indicated that exposure to exogenous hormones may cause hyperplasia of endocervical glands (11–15). Specifically, microglandular hyperplasia has been associated with exposure to exogenous progestins, although a recent study has raised questions about this association (11,12,16). The lesion presented here has many features in common with microglandular hyperplasia, including glandular proliferation and prominent acute inflammation. It is possible that the combination of stimulation of endocervical glands by exogenous hormones and abnormally viscous mucin due to CF resulted in a hyperplastic endocervical proliferation with markedly dilated glands and deep extension into the endocervical stroma in this patient. In the case presented here, the patient developed a remarkably florid proliferation of endocervical glands. Understandably, these features were initially worrisome for a malignant process. However, the absence of cytologic atypia, the lack of infiltration, a low rate of proliferation, and knowledge of the patient’s history of CF indicated that this was, instead, a benign lesion. This case, together with those in previous studies, suggests that women with CF can develop proliferative endocervical lesions and that oral contraceptives may contribute to their development. These findings indicate that it would be prudent to exercise caution when considering a diagnosis of well-differentiated endocervical adenocarcinoma in patients with CF and that further studies of the histopathologic changes of the cervix in CF are needed.
REFERENCES 1. Kopito LE, Kosasky HJ, Shwachman H. Water and electrolytes in cervical mucus from patients with cystic fibrosis. Fertil Steril 1973;24:512–6. 2. Gervais R, Dumur V, Letombe B, et al. Hypofertility with thick cervical mucus: another mild form of cystic fibrosis? JAMA 1996;276:1638. 3. Hilman BC, Aitken ML, Constantinescu M. Pregnancy in patients with cystic fibrosis. Clin Obstet Gynecol 1996;39:70–86. 4. Odegaard I, Stray-Pedersen B, Hallberg K, et al. Prevalence and outcome of pregnancies in Norwegian and Swedish women with cystic fibrosis. Acta Obstet Gynecol Scand 2002;81: 693–7. 5. Hodges CA, Palmert MR, Drumm ML. Infertility in females with cystic fibrosis is multifactorial: evidence from mouse models. Endocrinology 2008;149:2790–7. 6. Schoyer KD, Gilbert F, Rosenwaks A. Infertility and abnormal cervical mucus in two sisters who are compound heterozygotes for the cystic fibrosis (CF) DeltaF508 and R117H/7T mutations. Fertil Steril 2008;90:1201 e1219–22.
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7. Oppenheimer EH, Esterly JR. Observations on cystic fibrosis of the pancreas. VI. The uterine cervix. J Pediatr 1970;77: 991–5. 8. Oppenheimer EA, Case AL, Esterly JR, et al. Cervical mucus in cystic fibrosis: a possible cause of infertility. Am J Obstet Gynecol 1970;108:673–4. 9. Dooley RR, Braunstein H, Osher AB. Polypoid cervicitis in cystic fibrosis patients receiving oral contraceptives. Am J Obstet Gynecol 1974;118:971–4. 10. Oppenheimer EH, Esterly JR. Cystic fibrosis of the pancreas. Morphologic findings in infants with and without diagnostic pancreatic lesions. Arch Pathol 1973;96:149–54. 11. Taylor HB, Irey NS, Norris HJ. Atypical endocervical hyperplasia in women taking oral contraceptives. JAMA 1967; 202:637–9.
Int J Gynecol Pathol Vol. 33, No. 1, January 2014
12. Kyriakos M, Kempson RL, Konikov NF. A clinical and pathologic study of endocervical lesions associated with oral contraceptives. Cancer 1968;22:99–110. 13. Mingeot R, Fievez C. Endocervical changes with the use of synthetic steroids. Obstet Gynecol 1974;44:53–9. 14. Moltz L, Becker K. Cribriform polypoid adenomatous (atypical) hyperplasia of the endocervical glands of the uterus under hormonal contraception. Eur J Obstet Gynecol Reprod Biol 1977;7:331–6. 15. Johannisson E. Effects on the endometrium, endo- and exocervix following the use of local progestogen-releasing delivery systems. Contraception 1990;42:403–21. 16. Greeley C, Schroeder S, Silverberg SG. Microglandular hyperplasia of the cervix: a true ‘‘pill’’ lesion? Int J Gynecol Pathol 1995;14:50–4.
Case Report
Cystic Fibrosis Involving the Cervix, Mimicking a Well-differentiated Adenocarcinoma: A Case Report Rebecca A. Previs, M.D., James M. Edwards, M.D., Angeles A. Secord, M.D., Marisa R. Nucci, M.D., Rex C. Bentley, M.D., and Allison H. S. Hall, M.D.
Summary: We describe clinicopathologic and immunohistochemical features of an unusual case of cystic fibrosis manifesting in the cervix as a mass lesion, mimicking cervical adenocarcinoma. A 24-year-old nulligravida with cystic fibrosis developed heavy postcoital vaginal bleeding 4 months after starting oral contraceptives and was found to have a cervical mass. She underwent a loop electrosurgical excision of the mass, and microscopic examination revealed a florid endocervical proliferation, extending to the margins. This lesion was initially interpreted as an invasive, welldifferentiated endocervical adenocarcinoma. However, on subsequent review, the lesion was found to have a low rate of proliferation, no evidence of an infiltrative growth pattern, and abundant acute inflammation. Given these findings and the absence of any residual endocervical lesion on a subsequent cold knife conization, we determined that this was a benign, likely reactive, lesion. This case, together with previous studies, suggests that women with cystic fibrosis can develop proliferative endocervical lesions and that oral contraceptives may contribute to their development. Key Words: Cervical carcinoma—Cystic fibrosis—Endocervical hyperplasia—Oral contraceptives.
endocervical proliferation that was initially interpreted as a malignant lesion.
Cystic fibrosis (CF) is the most common lifethreatening genetic disease in the United States. Changes in the respiratory tract, gastrointestinal tract, and male reproductive tract related to CF have been well described. In contrast, the effects of CF on the female reproductive tract are less well understood. Here, we present the case of a young woman with CF who developed a benign, but florid
CASE REPORT A 24-year-old nulligravida with a past medical history significant for CF, bilateral lung transplantation, insulin-dependent diabetes mellitus, chronic pancreatitis, chronic sinusitis, and gastroparesis presented to her primary gynecologist with a 4-month history of postcoital bleeding. She had normal pap smears in the preceding 3 years and had received the Gardasil vaccine at the age of 21. Before her presentation, she had been amenorrheic for over 1½ years after her transplant. She started on microgestin for contraception. She resumed normal menses after 4 months and concomitantly developed heavy postcoital spotting. Evaluation began with pelvic ultrasound, which revealed a normal-sized uterus with a 6.8-mm endometrial stripe and a cervical mass
From the Department of Obstetrics and Gynecology (A.A.S.), Division of Gynecologic Oncology, Duke Cancer Institute; Departments of Obstetrics and Gynecology (R.A.P., J.M.E.); Pathology (R.C.B., A.H.S.H.), Duke University Medical Center, Durham, North Carolina; and Department of Pathology (M.R.N.), Division of Women’s and Perinatal Pathology, Brigham and Women’s Hospital, Boston, Massachusetts. The authors declare no conflict of interest. Address correspondence and reprint requests to Rebecca A. Previs, MD, Department of Obstetrics and Gynecology, Duke University Medical Center, P.O. Box 3616, Durham, NC 27710. E-mail: [email protected].
DOI: 10.1097/PGP.0b013e318278b832
100
CYSTIC FIBROSIS INVOLVING THE CERVIX described as a 3-cm friable, ectropion on the posterior lip of the cervix. A biopsy of the cervical mass was reported to show mild dysplasia. Of note, she discontinued her oral contraceptives at this time. A loop electrosurgical excision procedure was performed. The cervical excision specimen was reported to have a 2.5-cm papillary lesion on the mucosal surface. The stromal margin and the cut surfaces of the specimen were described as diffusely green-gray and mucinous. Microscopic examination revealed a proliferation of large, dilated mucinous glands with prominent acute inflammation (Fig. 1). The epithelium was focally hyperplasic, with papillary and microcystic growth patterns. Mitotic figures were very rare, and there was no significant cytologic atypia. The dilated glands extended 0.7 cm into the cervical stroma, involving the surgical margins. The glandular proliferation showed moderate to strong staining for CEA, focal, weak staining for p16 and p53, and showed a modest
101
rate of proliferation by Ki-67 staining, which was positive in 10% to 20% of glandular cells (Fig. 2). The pathology results were initially interpreted as an invasive, well-differentiated endocervical adenocarcinoma. Her postoperative physical examination was significant for multiple scattered papules around the clitoral hood and perineum consistent with condylomatous and dysplastic changes. There were no visible lesions on the cervix or vagina. Bimanual examination confirmed a small, mobile uterus with no cervical nodularity. Positron emission tomography/computed tomography showed no cervical mass or hypermetabolic activity in the cervical region, and no evidence of metastasis. The slides from the patient’s original cervical excision were reviewed and immunohistochemical stainings were performed. Given the lack of significant cytologic atypia, the low rate of proliferation,
FIG. 1. Endocervical proliferation with dilated glands extending deep into the endocervical stroma (A, 20 ). The epithelium has microcystic and papillary growth patterns and there is prominent acute inflammation (B, 100 ). The nuclei are regular with no significant cytologic atypia (C, D, 400 ).
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FIG. 2. An immunohistochemical stain for Ki-67 shows a low rate of proliferation in the endocervical epithelium (A, 200 ). There is moderate to strong expression of CEA (B, 200 ), minimal expression of p16 (C, 200 ), and focal, weak expression of p53 (D, 200 ).
the absence of a truly infiltrative growth pattern, and the presence of abundant acute inflammation, we interpreted the lesion as a reactive process rather than a malignancy. Because the morphologic findings are similar to the glandular dilation and hyperplasia seen in other organ systems affected by CF, we felt that this could be a CF-related lesion. The specimen was sent for an additional outside consultation with concordant results. Because the proliferation extended to the loop electrosurgical excision procedure specimen margins, a cold knife conization was performed to further evaluate the lesion. Colposcopy of the vagina, cervix, and vulva and vulvar biopsies was also performed, as was a laparoscopic bilateral salpingectomy, at the patient’s request. Colposcopy of the cervix revealed acetowhite changes involving all 4 quadrants, but no evidence of abnormal vasculature. No vaginal lesions were appreciated. Vulvar colposcopy showed white leukoplakia involving the right labium minus and Int J Gynecol Pathol Vol. 33, No. 1, January 2014
upper part of the right labium majus. Small punctuate lesions were visible bilaterally. Representative biopsies were performed. On laparoscopic survey, the abdominal and pelvic anatomy appeared normal except for 2 small tracts between the stomach and jejunum to the abdominal wall, consistent with prior feeding tubes. The cervical conization specimen had no grossly apparent lesions. Microscopic examination revealed low-grade dysplasia (CIN-1) of the ectocervical epithelium, with prominent human papillomavirus cytopathic effect. The endocervical glands were unremarkable, with no residual hyperplasia. The endocervical epithelium was negative for p16 and showed a low rate of proliferation by Ki-67 staining (positive in 10%–20% of glandular cells). Vulvar biopsies performed at the same time also showed lowgrade dysplasia (VIN-1). Given the bland appearance of the endocervical proliferation in the loop electrosurgical excision procedure specimen and the absence
CYSTIC FIBROSIS INVOLVING THE CERVIX of any residual abnormality in the cold knife conization, we feel that this lesion is best described as a benign hyperplasia of the endocervical glands. DISCUSSION This case highlights effects of CF on the cervical epithelium that can mimic a well-differentiated invasive cervical cancer. Histologic abnormalities of the cervix associated with CF have received relatively little attention. However, it is known that women with CF have abnormally thick, dehydrated cervical mucus, which may contribute to infertility and hypofertility in some patients (1–6). In one of the few studies that addresses cervical pathology in patients with CF, Oppenheimer and Esterly (7) evaluated the female genital tract of 36 girls with CF, aged 4 days to 15 years at the time of autopsy. They found increased extracellular and intracellular mucin in the endocervical glands of all newborns and approximately half of older children with CF. Only 2 of these patients were peripubescent. This same group reported a single case of a young woman with CF who was found to have a benign endocervical polyp characterized by dilated glands and mucin-filled cysts (8). In addition, Dooley et al. (9) described three cases of young women with CF who developed inflammatory cervical polyps while on oral contraceptives. The women ranged in age from 22 to 26 and developed the cervical polyps between 2 months and 1 year after initiation of oral contraceptive therapy. On histologic examination, the polyps showed endocervical glandular proliferation and prominent inflammatory infiltrates consisting of neutrophils, plasma cells, and lymphocytes. All of the lesions regressed after oral contraceptives were discontinued. The findings in this case series are particularly interesting in light of the case presented here. The patient in the current report is also of 22 years old and developed an endocervical lesion with hyperplastic endocervical glands and conspicuous acute inflammation within a year of starting oral contraceptive therapy. There are several lines of evidence to suggest that this patient’s lesion could be related to her history of CF. Women with CF have abnormal, very viscous mucus, which could contribute to the marked glandular dilation observed in this case (1,2,6). Also, CF patients are known to develop similar hyperplastic lesions of mucous glands in the gall bladder, salivary gland, gastrointestinal tract, and respiratory tract (10).
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There is also evidence to support the idea that oral contraceptives could have contributed to the development of this lesion. Previous studies have indicated that exposure to exogenous hormones may cause hyperplasia of endocervical glands (11–15). Specifically, microglandular hyperplasia has been associated with exposure to exogenous progestins, although a recent study has raised questions about this association (11,12,16). The lesion presented here has many features in common with microglandular hyperplasia, including glandular proliferation and prominent acute inflammation. It is possible that the combination of stimulation of endocervical glands by exogenous hormones and abnormally viscous mucin due to CF resulted in a hyperplastic endocervical proliferation with markedly dilated glands and deep extension into the endocervical stroma in this patient. In the case presented here, the patient developed a remarkably florid proliferation of endocervical glands. Understandably, these features were initially worrisome for a malignant process. However, the absence of cytologic atypia, the lack of infiltration, a low rate of proliferation, and knowledge of the patient’s history of CF indicated that this was, instead, a benign lesion. This case, together with those in previous studies, suggests that women with CF can develop proliferative endocervical lesions and that oral contraceptives may contribute to their development. These findings indicate that it would be prudent to exercise caution when considering a diagnosis of well-differentiated endocervical adenocarcinoma in patients with CF and that further studies of the histopathologic changes of the cervix in CF are needed.
REFERENCES 1. Kopito LE, Kosasky HJ, Shwachman H. Water and electrolytes in cervical mucus from patients with cystic fibrosis. Fertil Steril 1973;24:512–6. 2. Gervais R, Dumur V, Letombe B, et al. Hypofertility with thick cervical mucus: another mild form of cystic fibrosis? JAMA 1996;276:1638. 3. Hilman BC, Aitken ML, Constantinescu M. Pregnancy in patients with cystic fibrosis. Clin Obstet Gynecol 1996;39:70–86. 4. Odegaard I, Stray-Pedersen B, Hallberg K, et al. Prevalence and outcome of pregnancies in Norwegian and Swedish women with cystic fibrosis. Acta Obstet Gynecol Scand 2002;81: 693–7. 5. Hodges CA, Palmert MR, Drumm ML. Infertility in females with cystic fibrosis is multifactorial: evidence from mouse models. Endocrinology 2008;149:2790–7. 6. Schoyer KD, Gilbert F, Rosenwaks A. Infertility and abnormal cervical mucus in two sisters who are compound heterozygotes for the cystic fibrosis (CF) DeltaF508 and R117H/7T mutations. Fertil Steril 2008;90:1201 e1219–22.
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7. Oppenheimer EH, Esterly JR. Observations on cystic fibrosis of the pancreas. VI. The uterine cervix. J Pediatr 1970;77: 991–5. 8. Oppenheimer EA, Case AL, Esterly JR, et al. Cervical mucus in cystic fibrosis: a possible cause of infertility. Am J Obstet Gynecol 1970;108:673–4. 9. Dooley RR, Braunstein H, Osher AB. Polypoid cervicitis in cystic fibrosis patients receiving oral contraceptives. Am J Obstet Gynecol 1974;118:971–4. 10. Oppenheimer EH, Esterly JR. Cystic fibrosis of the pancreas. Morphologic findings in infants with and without diagnostic pancreatic lesions. Arch Pathol 1973;96:149–54. 11. Taylor HB, Irey NS, Norris HJ. Atypical endocervical hyperplasia in women taking oral contraceptives. JAMA 1967; 202:637–9.
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12. Kyriakos M, Kempson RL, Konikov NF. A clinical and pathologic study of endocervical lesions associated with oral contraceptives. Cancer 1968;22:99–110. 13. Mingeot R, Fievez C. Endocervical changes with the use of synthetic steroids. Obstet Gynecol 1974;44:53–9. 14. Moltz L, Becker K. Cribriform polypoid adenomatous (atypical) hyperplasia of the endocervical glands of the uterus under hormonal contraception. Eur J Obstet Gynecol Reprod Biol 1977;7:331–6. 15. Johannisson E. Effects on the endometrium, endo- and exocervix following the use of local progestogen-releasing delivery systems. Contraception 1990;42:403–21. 16. Greeley C, Schroeder S, Silverberg SG. Microglandular hyperplasia of the cervix: a true ‘‘pill’’ lesion? Int J Gynecol Pathol 1995;14:50–4.
