Monday, December 1, 2014

Cervical cancer in PJS

There is a rare cervical cancer associated with Peutz-Jeghers syndrome, adenoma malignum of the uterine cervix or minimal deviation adenocarcinoma of the uterine cervix.

Unlike most cervical cancers, it starts inside the cervix instead of on the outer lining.

It's hard to diagnose because of its location. PAP smears won't find it and a different type of biopsy is needed.

Women who've had AM/MDA report mucous or watery discharge, bleeding between periods, heavy bleeding, pain, hyperestrogenism and pain.

A list of article abstracts follows.

Please feel free to print and take to your doctor.

I am not a medical professional and am not diagnosing, treating or prescribing.

My best medical advice is to get the best medical advice!

1. Future Oncol. 2014 Feb;10(2):171-7. doi: 10.2217/fon.13.180.

A tumor of the uterine cervix with a complex histology in a Peutz-Jeghers syndrome patient with genomic deletion of the STK11 exon 1 region.

Kobayashi Y(1), Masuda K, Kimura T, Nomura H, Hirasawa A, Banno K, Susumu N, Sugano K, Aoki D.

Patients with Peutz-Jeghers syndrome (PJS) have a risk of complicating malignant tumors, including cancer of the uterine cervix. Mutations in the STK11 gene have been identified as being responsible for PJS. However, the genotype-phenotype correlation in PJS is poorly understood, especially with respect to malignant tumors. Here, we report a detailed analysis of a case of a cervical tumor in a PJS patient showing a large genomic deletion in exon 1 of STK11 without human papillomavirus infection. Histological examination revealed a complex histology consisting of three components: lobular endocervical gland hyperplasia (LEGH), minimal deviation adenocarcinoma (MDA) and mucinous adenocarcinoma.
Immunohistochemistry for STK11 was positive in the LEGH and MDA components, while that of the mucinous adenocarcinoma stained very faintly. These findings support a close relationship among LEGH, MDA and mucinous adenocarcinoma and imply that inactivation of STK11 may occur during progression from MDA to mucinous adenocarcinoma.

PMID: 24490603  [PubMed - in process]

2. Oncol Lett. 2013 Nov;6(5):1184-1188. Epub 2013 Aug 16.

Hereditary gynecological tumors associated with Peutz-Jeghers syndrome (Review).

Banno K(1), Kisu I, Yanokura M, Masuda K, Ueki A, Kobayashi Y, Hirasawa A, Aoki

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease that is characterized by gastrointestinal hamartomatous polyposis and mucocutaneous melanin spots. The tumor suppressor gene, STK11/LKB1, which is located on chromosome 19p13.3, has been reported to be responsible for this condition. PJS is complicated by benign and malignant tumors of various organs and complications from rare diseases, including sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which have also recently attracted attention in the field of gynecology. Among the total MDA cases, 10% are complications of PJS, and mutations in the STK11 gene are closely associated with the development and prognosis of MDA. Furthermore, a new type of uterine cervical tumor, lobular endocervical glandular hyperplasia (LEGH), has been identified and has been predicted to be a precancerous lesion of MDA. The first case of LEGH induced by a germline STK11 mutation has also been described. A high risk of endometrial cancer in PJS has also been reported. These developments suggest that PJS is an important syndrome of hereditary gynecological tumors that requires further study.

PMCID: PMC3813608
PMID: 24179492  [PubMed]

3. J Gynecol Oncol. 2013 Jan;24(1):92-5. doi: 10.3802/jgo.2013.24.1.92. Epub 2013 Jan 8.

Minimal deviation adenocarcinoma of the cervix and tumorlets of sex-cord stromal  tumor with annular tubules of the ovary in Peutz-Jeghers syndrome.

Kwon SY(1), Choe MS, Lee HW, Lee HJ, Shin SJ, Cho CH.

We report 2 cases of minimal deviation adenocarcinoma of the cervix and tumorlets of sex cord tumor with annular tubules (SCTATs) of the ovaries, accompanied by Peutz-Jeghers syndrome. Case 1 is a 36-year-old woman and case 2 is a 35-year-old woman. Grossly, the cervix of both cases showed markedly barrel shaped enlargement with an infiltrating tumor. Microscopically, well-differentiated atypical glands were infiltrating into the entire thickness of the cervix. The ovarian masses in case 1 were diagnosed as metastatic carcinoma in mucinous cystadenoma with tumorlets of SCTATs of the ovaries.
Multiple scattered tumorlets of SCTATs were also found in the ovary of case 2. By direct DNA sequencing analysis, a frame shift mutation of the STK11/LKB1 gene was identified in case 1.
Case 1 represented the more aggressive clinical course, and although the patient received additional combined chemo-radiation therapy, she expired 1 year later.
In general, mutation of the STK11/LKB1 gene is associated with poor clinical outcome in malignant tumors accompanied by Peutz-Jeghers syndrome.

PMCID: PMC3549513
PMID: 23346318  [PubMed]

4. Pathol Res Pract. 2012 Oct 15;208(10):623-7. doi: 10.1016/j.prp.2012.06.008.
Epub2012 Aug 9.

Peutz-Jeghers syndrome-associated atypical mucinous proliferation of the uterine cervix: a case of minimal deviation adenocarcinoma ('adenoma malignum') in situ.

Ito M(1), Minamiguchi S, Mikami Y, Ueda Y, Sekiyama K, Yamamoto T, Takakura K.

We describe a case of a non-invasive precursor of minimal deviation adenocarcinoma (MDA) of the uterine cervix, associated with Peutz-Jeghers syndrome (PJS). A 27-year-old woman, who had been followed for PJS, was referred to the gynecology clinic. Colposcopic examination demonstrated a small polypoid lesion in the transformation zone. Microscopic examination of the biopsy specimen demonstrated papillary proliferation of the mucinous epithelium with bland nuclear morphology. Conization revealed lobular endocervical glandular hyperplasia (LEGH) with distinct nuclear anaplasia, as well as papillary proliferation of the mucinous epithelium with mild to moderate nuclear abnormalities. This case suggests that the incipient phase of PJS-associated MDA is related to atypical LEGH ("MDA in situ"), and indicates the importance of early screening and surveillance by gynecologists in cases of PJS to detect cervical adenocarcinomas.

Copyright © 2012 Elsevier GmbH. All rights reserved.

PMID: 22878090  [PubMed - indexed for MEDLINE]

5. Eur J Gynaecol Oncol. 2011;32(4):452-4.

Endometrial carcinoma and ovarian sex cord tumor with annular tubules in a patient with history of Peutz-Jeghers syndrome and multiple malignancies.

Kondi-Pafiti A(1), Bakalianou K, Iavazzo C, Dastamani C, Hasiakos D, Liapis A.

Background: Peutz-Jeghers syndrome is a rare syndrome which is inherited in a dominant manner. It is characterized by hamartomatous polyps of the gastrointestinal tract, hyperpigmented macules of the oral mucosa and an increased risk of developing neoplasms in the gastrointestinal tract, pancreas, breast and genital system. Women with Peutz-Jeghers syndrome often develop an ovarian sex cord tumor and cervical adenocarcinoma of minimal deviation adenoma malignum type. A case of a 58-year-old patient with Peutz-Jeghers syndrome and history of multiple malignancies (thyroid, breast and colon cancer) who presented with metrorrhagia is reported. The dilatation and curettage revealed endometrial adenocarcinoma. The patient underwent total abdominal hysterectomy with bilateral oophorectomy. The histologic examination showed an endometrioid endometrial adenocarcinoma that developed in atypical endometrial hyperplasia.
The histologic examination of the right ovary revealed a sex cord tumor with annular tubules, measuring 3 cm. Sex cord tumors with annular tubules in patients with Peutz-Jeghers syndrome are usually small, bilateral tumors of the ovaries which have common characteristics with granulosa cell tumor and Sertoli cell tumor.
Hyperestrogenism is a rather common finding with development of estrogen-dependent lesions.

PMID: 21941977  [PubMed - indexed for MEDLINE]

6. J Gynecol Oncol. 2010 Sep;21(3):203-6. doi: 10.3802/jgo.2010.21.3.203. Epub 2010  Sep 28.

Co-occurrence of an adenoma malignum and an endocervical-type adenocarcinoma of the uterine cervix in a woman with Peutz-Jeghers syndrome.

Koo YJ(1), Lee JE, Hong SR, Kwon YS.

We report a rare co-occurrence of an adenoma malignum and an adenocarcinoma in a 30-year-old woman with Peutz-Jeghers syndrome. The woman was diagnosed with Peutz-Jeghers syndrome based on an endoscopic biopsy after vaginal bleeding. A pelvic examination and an MRI revealed the co-occurrence of a 4×5 cm protruding adenocarcinoma of FIGO stage Ib2 based on a punch biopsy and a 4.5×5.7 cm multilocular cystic mass above the solid cancer. The patient received two courses of neoadjuvant chemotherapy, followed by a laparoscopic radical hysterectomy with pelvic lymph node dissection. Pathologic findings were consistent with adenocarcinoma (40%) and adenoma malignum (60%) confined to the cervix. Three courses of adjuvant chemotherapy were performed and no clinical evidence of recurrence was seen during a 12 month follow-up period. This study will contribute to defining the best diagnosis and treatment for these rare complicating tumors.

PMCID: PMC2948231
PMID: 20922146  [PubMed]

7. J Med Assoc Thai. 2009 Dec;92(12):1686-90.

Female genital tract tumors and gastrointestinal lesions in the Peutz-Jeghers syndrome.

Tantipalakorn C(1), Khunamornpong S, Lertprasertsuke N, Tongsong T.

BACKGROUND: Peutz-Jeghers Syndrome (PJS) is a rare genetic disorder characterized by mucocutaneous melanin deposition, and intestinal hamartomatous polyps, with an increased risk of breast, gastrointestinal, and female genital tract cancers.

CASE REPORT: Multiple genital tract neoplasms in a 52-year-old northern Thai woman with PJS are described. The patient presented with abdominal distention. A pelvic ultrasound scan showed a left adnexal mass, diagnosed as mucinous cyst. An ovarian microscopic cystadenoma was diagnosed together with a minimal deviation mucinous adenocarcinoma (MDA) of the uterine cervix and mucinous metaplasia in tubal mucosa and endometrium. Pathological findings warranted a search for evidence of PJS Typical pigmentation at the hard palate and colonoscopic finding of hamartomatous polyps established the diagnosis of PJS.
At four-year follow-up, the patient still showed no evidence of tumor recurrence.

CONCLUSION: A case of PJS complicated by multiple and contemporaneous genital tract tumors with rare histological findings is presented. The presented case suggests MDA and mucinous metaplasia warrant a search for PJS.

PMID: 20043574  [PubMed - indexed for MEDLINE]

8. Int J Gynecol Cancer. 2009 Dec;19(9):1591-4. doi: 10.1111/IGC.0b013e3181ae3f71.

A case of Peutz-Jeghers syndrome with breast cancer, bilateral sex cord tumor with annular tubules, and adenoma malignum caused by STK11 gene mutation.

Clements A(1), Robison K, Granai C, Steinhoff MM, Scalia-Wilbur J, Moore RG.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder, and women with this syndrome are at an increased risk of developing intestinal and extraintestinal malignancies including breast and gynecologic malignancies.
This case report presents a patient with PJS with a concomitant breast cancer, bilateral stromal tumors with annular tubules of the ovaries, and adenoma malignum of the cervix.

CASE: A 43-year-old woman presented with an advanced-stage breast cancer and a pelvic mass. The patient was treated with neoadjuvant chemotherapy followed by laparotomy with a hysterectomy and oophorectomy. Final pathologic examination revealed a concomitant breast cancer with metastasis to the ovaries, bilateral stromal tumors with annular tubules of the ovaries, and adenoma malignum of the cervix.

CONCLUSIONS: Patients with PJS are at a high risk for intestinal and extraintestinal malignancies and can present with multiple concomitant malignancies.

PMID: 19955943  [PubMed - indexed for MEDLINE]

9. J Korean Med Sci. 2006 Aug;21(4):752-7.

Peutz-Jeghers Syndrome with multiple genital tract tumors and breast cancer: a case report with a review of literatures.

Song SH(1), Lee JK, Saw HS, Choi SY, Koo BH, Kim A, Yeom BW, Kim I.

We report here on the multiple genital tract neoplasms in a 41-yr-old Korean woman with Peutz-Jeghers Syndrome (PJS). The patient presented with lower abdominal pain. Her previous medical history was PJS and breast cancer. Pelvic ultrasound showed a multilocular cyst at the right adnexal region, diagnosed as bilateral ovarian mucinous borderline tumors. An ovarian sex cord tumor with annular tubules was incidentally diagnosed together with a minimal deviation adenocarcinoma of the uterine cervix and mucinous metaplasia of both the Fallopian tubal mucosa and the endometrium. Although the cases of multiple genital tract tumors with PJS has rarely been reported, the present case appears to be the first in Korea in which the PJS syndrome was complicated by multiple genital tract tumors and infiltrating carcinoma of the breast. The clinical significance of the multiple genital tract tumors and breast cancer associated with PJS is reviewed.

PMCID: PMC2729904
PMID: 16891826  [PubMed - indexed for MEDLINE]

10. Gynecol Oncol. 2004 Jan;92(1):337-42.

An unusual admixture of neoplastic and metaplastic lesions of the female genital  tract in the Peutz-Jeghers Syndrome.

Mangili G(1), Taccagni G, Garavaglia E, Carnelli M, Montoli S.

BACKGROUND: Peutz-Jeghers Syndrome (PJS) is a rare autosomal dominant condition with variable penetrance characterized by gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. Patients with PJS have an increased risk for breast, gastrointestinal and female genital tract cancers.
CASE: Multiple genital tract neoplasms in a 41-year-old Italian woman with PJS are described. The patient presented with abdominal pain due to intussusception.
A CT scan of the abdomen also showed a left adnexal mass, diagnosed as ovarian mixed serous and mucinous borderline tumor. An ovarian microscopic sex cord tumor with annular tubules (SCTAT) was incidentally diagnosed together with a minimal deviation mucinous adenocarcinoma of the uterine cervix. Also areas of typical hyperplasia of the tubal mucosa with mucinous metaplasia were found.

CONCLUSION: This appears to be one of the rare cases reported in literature in which PJS is complicated by multiple and contemporaneous genital tract tumors and rare histological findings. The clinical significance of recurrence of these unusual genital tract tumors and histological alterations in PJS patients is reviewed.

PMID: 14751181  [PubMed - indexed for MEDLINE]

11. Ann Pathol. 1997 Jul;17(3):193-5.

[Minimal deviation adenocarcinoma of the uterine cervix in a woman with
Peutz-Jeghers syndrome. Report of a case].

[Article in French]

Chatti S(1), Bellil K, Jerbi G, Kchir N, Haouet S, Kacem M, Boubaker S, Zouari
F, Filali A, Chelli H, Rahal K, Zitouna M.

We report a case of minimal deviation adenocarcinoma of the uterine cervix in a 32 year old women who present a Peutz Jeghers syndrome. This patient also had fibroadenoma of the breast and dystrophic mastopathy. This case represents an example of predisposition to developing tumors of the Peutz Jeghers syndrome.

PMID: 9296579  [PubMed - indexed for MEDLINE]

12. Int J Gynaecol Obstet. 1996 May;53(2):171-2.

Adenoma malignum of the uterine cervix associated with Peutz-Jeghers syndrome.

Fujiwaki R, Takahashi K, Kitao M.

PMID: 8735299  [PubMed - indexed for MEDLINE]

13. Gynecol Oncol. 1994 Aug;54(2):232-6.

Adenoma malignum of the uterine cervix detected by imaging methods in a patient with Peutz-Jeghers syndrome.

Tsuruchi N(1), Tsukamoto N, Kaku T, Kamura T, Nakano H.

Adenoma malignum of the uterine cervix in a 25-year-old Japanese woman with Peutz-Jeghers syndrome (PJS) is described. A cervical multicystic mass was detected by CT scan, sonography, and MR imaging. These imaging findings strongly suggested the presence of adenoma malignum in spite of normal Pap smear, colposcopy, and cervical biopsy reports. Radical hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and para-aortic lymph node biopsy  were performed after confirmation of adenoma malignum by conization. Both ovaries showed multicentric sex cord tumor with annular tubules. She is alive and well with no evidence of disease 23 months after surgery. Imaging methods including sonography, CT scan, and MR imaging may be useful aids in detecting the presence  of adenoma malignum, especially in patients with PJS.

PMID: 8063253  [PubMed - indexed for MEDLINE]

14. Gynecol Oncol. 1994 May;53(2):256-64.

Disseminated cervical adenoma malignum and bilateral ovarian sex cord tumors with annular tubules associated with Peutz-Jeghers syndrome.

Srivatsa PJ(1), Keeney GL, Podratz KC.

Adenoma malignum is a highly differentiated mucinous adenocarcinoma of the cervix with a deceptively innocent histologic appearance but a highly aggressive behavior. We describe a patient who had adenoma malignum associated with Peutz-Jeghers syndrome (PJS) and bilateral ovarian sex cord tumor with annular tubules (SCTAT). The relatively frequent occurrence of cervical adenoma malignum  in women with PJS warrants close surveillance by gynecologists for early detection and treatment of this cancer. We report the 16th known case of PJS with adenoma malignum and only the 8th known case of PJS with adenoma malignum and bilateral SCTAT. The highly aggressive nature of cervical adenoma malignum is exemplified, and the difficulties associated with early diagnosis are discussed.
The clinical significance of cervical and ovarian tumors associated with PJS is reviewed.

PMID: 8188091  [PubMed - indexed for MEDLINE]

15. J Comput Assist Tomogr. 1993 Sep-Oct;17(5):819-21.

Adenoma malignum of uterine cervix in Peutz-Jeghers syndrome: CT and US features.

Choi CG(1), Kim SH, Kim JS, Chi JG, Song ES, Han MC.

We report CT and ultrasound (US) features of adenoma malignum of the uterine cervix in a patient with Peutz-Jeghers syndrome (PJS) in whom bilateral ovarian mucinous cystadenomas and sex cord tumors with annular tubules were associated.
Adenoma malignum was shown as a hyperechoic mass mixed with multiple cysts on US and a low attenuated endocervical mass on CT. We think that imaging demonstration of an endocervical mass is important for the correct diagnosis of adenoma malignum in a female with PJS.

PMID: 8370843  [PubMed - indexed for MEDLINE]

16. Gynecol Oncol. 1991 Jul;42(1):74-8.

Peutz-Jeghers syndrome with ovarian sex cord tumor with annular tubules and cervical adenoma malignum.

Podczaski E(1), Kaminski PF, Pees RC, Singapuri K, Sorosky JI.

A patient with Peutz-Jeghers syndrome, a sex cord tumor with annular tubules, and an initially unrecognized adenoma malignum of the cervix is described. The patient presented with a mucinous adenocarcinoma in the vaginal apex. Review of the hysterectomy slides demonstrated an adenoma malignum of the cervix. In addition to a microscopic sex cord tumor with annular tubules of the right ovary, the left ovary contained mucinous cystadenomas. Adenoma malignum remains a difficult diagnosis and is frequently made only after hysterectomy for a presumed benign indication; pathology frequently demonstrates a deeply invasive, unusually well differentiated adenocarcinoma of the cervix. Patients with Peutz-Jeghers syndrome need careful clinical and cytologic follow-up to exclude such lesions.

PMID: 1916514  [PubMed - indexed for MEDLINE]

17. Br J Obstet Gynaecol. 1989 Sep;96(9):1101-4.

Peutz-Jeghers syndrome in association with adenoma malignum (minimal deviation adenocarcinoma) of the cervix. Case report.

Soeters R(1), Tiltman A, Learmonth G, Bloch B, Dehaeck K, Levin W.

PMID: 2804013  [PubMed - indexed for MEDLINE]

18. Am J Surg Pathol. 1989 Sep;13(9):717-29.

Adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix. A
clinicopathological and immunohistochemical analysis of 26 cases.

Gilks CB(1), Young RH, Aguirre P, DeLellis RA, Scully RE.

We reviewed 26 examples of the rare variant of cervical adenocarcinoma that has been designated "adenoma malignum." The patients, three of whom had Peutz-Jeghers syndrome, ranged in age from 25 to 72 years (average, 42 years).
The most common presenting symptom was menometrorrhagia, followed by vaginal discharge, postmenopausal bleeding, and abdominal swelling in decreasing order of frequency.
In 12 of the patients, the diagnosis was established on the basis of the examination of a cervical biopsy specimen, endocervical curettage specimen, or both. In three of these cases, however, up to four biopsies were performed before the diagnosis was established. In the remaining 14 patients, the diagnosis was not made until the time of operation or pathologic examination of a hysterectomy specimen. On gross examination, the cervix usually appeared abnormal, but occasional specimens were considered unremarkable. The cervix was typically described as firm or indurated. Microscopic examination showed glands that were irregular in size and shape and lined predominantly by mucin-containing columnar epithelial cells with basal nuclei. The tumors typically exhibited deep invasion of the cervical wall, and a portion of the infiltrating tumor was associated with a stromal response in most cases. Minor foci of tumor with a less well-differentiated appearance were present in 15 of the 26 tumors. Argyrophil cells were present in six of 15 tumors. Five of the six tumors containing argyrophil cells stained immunohistochemically for serotonin and peptide hormones. Positive staining for serotonin was seen in four tumors; one of these also contained a few cells positive for neurotensin.
Cytoplasmic staining of the tumor cells for carcinoembryonic antigen (CEA) was seen in five of six cases. CEA reactivity was very focal in two of the positive tumors. Microscopic features that were most helpful in distinguishing adenoma
malignum from normal endocervix  or benign endocervical glandular proliferations were the presence of markedly irregular, abnormally shaped glands; invasion of the cervical wall; a loose edematous or desmoplastic stromal response; foci of less well-differentiated tumor; vascular invasion; perineural invasion; and positive staining for CEA.
Despite radical therapy in most of the cases, the prognosis was poor. Follow-up data were available for 22 patients. Thirteen of them died of recurrent tumor, four were alive with recurrent tumor at the time of last follow-up examination, and only three patients were disease free for 2 years or more.

PMID: 2764221  [PubMed - indexed for MEDLINE]

19. Int J Gynecol Pathol. 1988;7(2):99-111.

Mucinous ovarian tumors associated with mucinous adenocarcinomas of the cervix.
A clinicopathological analysis of 16 cases.

Young RH(1), Scully RE.

Sixteen cases of mucinous adenocarcinoma of the cervix that were associated with  amucinous tumor of one or both ovaries are reported. The patients ranged from
25 to 70 (average, 44) years of age; two of them had the Peutz-Jeghers syndrome.
Eight patients complained of abdominal swelling; most of the remainder had symptoms of uterine origin. Twelve patients had bilateral and four had unilateral ovarian tumors, which were typically large and cystic. Microscopic examination of most of the ovarian tumors revealed various combinations of benign-appearing, borderline, and carcinomatous mucinous epithelium within the same specimen. Most of the cervical tumors were deeply invasive; 10 of them were of the adenoma malignum type. Although there were varying degrees of uncertainty in individual cases, consideration of several features including the extent and distribution of disease in the abdomen, the comparative histology of the tumors, and the pattern of ovarian involvement suggested that 10 of the ovarian tumors were independent primary tumors, three were metastatic from the cervix, and in three cases the ovaries contained both primary and metastatic tumors.

PMID: 2840404  [PubMed - indexed for MEDLINE]

20. Schweiz Med Wochenschr. 1987 Nov 28;117(48):1910-4.

[Adenocarcinoma of the cervix in Peutz-Jeghers syndrome. Case report and review of the literature].

[Article in German]

von Hochstetter AR(1), Ess D, Bannwart F, B├╝hler H.

The incidental finding of "adenoma malignum" or minimal deviation adenocarcinoma  (MDA) of the cervix in a 38-year-old woman with Peutz-Jeghers syndrome (PJS) is reported and the literature is discussed. This highly differentiated form of adenocarcinoma is extremely rare but, like some other rare neoplasms, may occur more frequently in patients with PJS syndrome. Since the prognosis of MDA is considered poor and the histological diagnosis is often missed on biopsy, the importance of closely correlating clinical and pathological findings is emphasized.

PMID: 3321428  [PubMed - indexed for MEDLINE]

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