- Email: [email protected]
Peritoneal Inclusion Cysts in Adolescent Females: A Clinicopathological Characterization of Four Cases
J Pediatr Adolesc Gynecol (2009) 22:41e48
Original Studies Peritoneal Inclusion Cysts in Adolescent Females: A Clinicopathological Characterization of Four Cases Lawrence S. Amesse, MD, PhD, HCLD1, Paul Gibbs, MD2, John Hardy, MD1, Kimberly R. Jones1, and Teresa Pfaff-Amesse, MD1 1
Section of Pediatric and Adolescent Gynecology, Department of Obstetrics and Gynecology, Wright State University Boonshoft School of Medicine; 2Department of Pathology, Miami Valley Hospital, Dayton, Ohio, USA
Abstract. Study Objective: To identify adolescent females with peritoneal inclusion cysts and characterize the clinicopathologic features. Design: Observational and chart review along with immunohistochemical studies. Setting: University pediatric and adolescent clinic. Results: Medical records of all subjects, ages 10e18 years, diagnosed with peritoneal inclusion cysts over a 4-year period were retrospectively reviewed. Four patients, ages 11e16 years (mean, 13.8 yrs) were identified. Pelvic pain was the most common presenting symptom. No palpable abdominal or pelvic masses were detected. However, pelvic lesions were identified by radiographic studies in three of the four patients. Half experienced tenderness on examination. With one exception, all had a prior history of abdominal surgery. Twelve peritoneal inclusion cysts were identified, ranging from 1 cm to 7 cm in greatest diameter. Most were uninvolved in coexisting adhesions and non-adherent to pelvic or abdominal structures. Each had a well-defined pedicle connection to the peritoneum. No associated complications were identified. Their appearance conformed to established morphologic and immunohistochemical criteria, although accompanying mesothelial-associated changes occasionally reported in other populations were not detected. No recurrences were recorded. Conclusion: Young female adolescents with peritoneal inclusion cysts share presenting symptoms and histories of previous abdominal surgery similar to those reported in older female adolescents and adults. A palpable mass may not be detected on examination, but can often be identified using radiographic studies. Our cases differ from previous reports by smaller cyst size, presence of a pedicle, and uncomplicated gross and microscopic appearances. Additionally, local recurrences and associated complications occurred less than reported in adults.
Key Words. Peritoneal inclusion cysts—Adolescent females—Benign cystic mesothelioma—Multicystic mesothelioma—Inflammatory cysts of the peritoneum
Introduction
Address corsrespondence to: Lawrence S. Amesse, MD, PhD, Department of Obstetrics and Gynecology, Wright State University, Boonshoft School of Medicine, 128 E. Apple Street, Suite 3800 CHE, Dayton, Ohio 45409-2793.; E-mail: [email protected]
Peritoneal inclusion cysts are unusual lesions that usually occur in the pelvis of reproductive-age women. Although benign, local recurrences are common, often requiring repeated surgeries.1e9 The average age at diagnosis is approximately 32 years, with reported ages ranging from 17 to 61 years.9,10 In adult females, there is often a prior history of abdominal surgery, pelvic inflammatory disease (PID) or endometriosis.7e10 The most common presenting symptom is lower abdominal or pelvic pain. In some cases, a palpable mass can be detected. The cysts are often multiple, ranging from 1 cm to O20 cm in greatest diameter, with some forming confluent masses that fill the pelvis.11,12 They often adhere to pelvic and abdominal structures, yet some are free-floating in the peritoneum.4,7e9 Some experts consider these lesions a true neoplasm, while others advocate a reactive process. This dichotomy in pathogenesis is reflected by the various terms used to designate them, including benign cystic mesothelioma, multicystic mesothelioma, and inflammatory cysts of the peritoneum.8,9 Although this entity is predominantly diagnosed in reproductive-age females, well-documented cases of peritoneal inclusion cysts have been described in menopausal women, men, and preadolescent children.2,5,13e17 Reports of these cysts occurring in adolescent females are rare. Indeed, only four cases have been reported in the last 20 years.7,9,10 We describe our experience with four female adolescents diagnosed with peritoneal inclusion cysts, characterize
Ó 2009 North American Society for Pediatric and Adolescent Gynecology Published by Elsevier Inc.
1083-3188/09/$34.00 doi:10.1016/j.jpag.2008.02.003
42
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
the clinicopathologic features, and include a review of the literature. Methods The medical records at the Pediatric/Adolescent Section, Department of Obstetrics and Gynecology, at Miami Valley Hospital, and the Gynecology Service at Children’s Hospital Medical Center were searched for all patients, ages 10 to 18 years, diagnosed with peritoneal inclusion cysts between January 2002 and December 2006. Four patients were identified and imaging studies, pathology reports and histology slides were reviewed. Paraffin blocks were retrieved from archives. Follow-up data were obtained in three cases from the medical records and office visits. Hematoxylin and eosin-stained glass slides from each case were examined. All cases fulfilling the following standard histological criteria were included: uni- or multilocular cysts; single layer of mesothelial cells; fibrovascular septa; and no evidence of smooth muscle. The slides were also examined for the following mesothelial-associated changes and growth patterns occasionally described in previous reports: mural mesothelial proliferations, adenomatoid tumor-like patterns, squamous metaplasia, glands, nests, small papillae or cribiform pattern, xanthomatous changes, endometriosis and cytologic atypia.7e10 Representative sections from each case were selected for immunohistochemical studies to confirm the mesothelial cell origin. Immunostaining was performed as previously described with modified label avidin-biotin peroxidase complex method and Dako Cytomation Autostainer (Dako Cytomation Corp., Carpinteria, CA) the only modifications.18 The following mouse primary monoclonal IgG1 antibodies and their respective dilutions were used: cytokeratin (CK) 5/6 (1:1100) (Biocare Medical, Clone CK5/ 6.007, Concord, CA); carcinoembryonic antigen (CEA) (1:400) and CD 175 or B72.3 (1:100) (Dako Cytomation Corp., Clone II-7 and Clone HB-STn1, respectively, Carpinteria, CA). The rabbit polyclonal antibody to calretinin (1:100) (Zymed Laboratories, Clones DC8, San Francisco, CA) was also used as a primary antibody. Results Clinical Findings Case 1. L.M. was an 11-year-old nulliparous adolescent with a last menstrual period 6 weeks prior to presentation who complained of pelvic pain, refractory to medical therapy, of 4 months duration. The patient was 7 months status post laparoscopic appendectomy. Gastrointestinal and genitourinary symptoms as well as sexual activity were denied. The medical history
was negative for PID and endometriosis. Physical examination revealed moderate abdominal tenderness, mild guarding, and absent rebound tenderness. Transabdominal ultrasound of the pelvis revealed a 19- mm cystic mass within an enlarged right ovary, considered consistent with a hemorrhagic ovarian cyst. A complex cystic 5.5 cm 2.2 cm mass was also detected in the cul de sac (Fig. 1A). Extensive adhesions were identified on laparoscopy. Three multiloculated cysts were found in the cul de sac and each was connected to the peritoneum by a pedicle. They did not adhere to pelvic structures and were uninvolved with adhesions. The largest measured 4 cm 5 cm and was attached to the anterior pelvic wall peritoneum, with the cyst proper extending into the cul de sac, adjacent to the ovaries. Budding off the superior aspect of the same pedicle was a smaller, similar appearing 2 cm 3 cm cyst. The pedicle of the third cyst, which measured 3 cm 5 cm, originated from the cul de sac peritoneum. The cysts were translucent and filled with clear serous fluid (Fig. 1B, C). After adhesion lyses, the cysts were removed and sent to pathology.
Case 2. A.K. was a 13-year-old menarchal, nulligravida referred for evaluation of pelvic pain, refractory to medical management, of several months duration. Nineteen months prior to referral, she underwent a right oophorectomy and left ovarian wedge resection for ovarian torsion and cysts, respectively. There was no history of PID or endometriosis. Pelvic examination revealed minimal lower abdominal tenderness with no palpable masses. The transabdominal pelvic ultrasound was unremarkable. Laparoscopic examination revealed extensive pelvic, omental and abdominal adhesions. Two multiloculated cysts (range, 4 cme7 cm in greatest diameter) were identified in the cul de sac, adjacent to the ovaries (Fig. 2). They were uninvolved with adhesions and did not adhere to the surface of the ovaries, tubes, uterus or other structures. The initial impression was that they were paratubal in origin. However, upon exploration and dissection, they were discovered to have pedicle attachments to different sites of the anterior pelvic peritoneum. They were translucent, contained clear, serous fluid, and collapsed upon resection.
Case 3. L.H. was a 16-year-old, nulliparous teenager referred for evaluation of pelvic pain and fever of 4 days duration, unresponsive to antibiotic therapy, with an episode of acute hypotension. She was 2 years, 9 months status post open appendectomy for a perforated appendix. The history of PID and endometriosis
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
43
Fig. 1. Case 1. (A) Transabdominal ultrasound of the pelvis. Peritoneal inclusion cysts, located in the cul de sac, are designated by an arrow. (B, C) In situ findings of two peritoneal inclusion cysts. The pedicle connection to the peritoneum is designated by an arrow in B.
was negative. Sexual activity was denied and the bhCG was negative. A transabdominal ultrasound of the pelvis and kidneys identified a 5 cm 2 cm heterogeneous, complex fluid-filled cystic lesion, considered consistent with a tuboovarian abscess, abutting the left ovary along the posterior aspect of the uterus. An incidental right extrarenal pelvis was also identified. No additional developmental anomalies were detected. Similar findings were identified on the pelvic computed tomography (CT) (Fig. 3A). The pelvis was encased in extensive fibrous adhesions, forming a ‘‘frozen pelvis’’ with omental and bowel adhesions also evident on laparoscopic examination. Bilateral hydrosalpinx and tubal occlusions were identified, but there was no evidence of a tuboovarian abscess. Four cysts, ranging from 1.5 cm 2 cm to 3.2 cm 3.6 cm in greatest dimension, were identified in the cul de sac and were involved in adhesions. Some adhered to the ovarian surfaces and others, to the uterine and tubal serosa. The initial impression was that they represented benign ovarian
Fig. 2. Case 2. Multiloculated peritoneal inclusion cyst. The arrow indicates the inferior aspect of the pedicle, with the translucent cyst apparent.
cysts or florid cystic endosalpingiosis. However, upon dissection, all originated at the cul de sac peritoneum where they were connected by a pedicle (Fig. 3B). Case 4. J.P. was 15-year-old nulliparous, menarchal adolescent referred for resection of a cystic ovarian mass. The patient was evaluated by CT scan for recurrent urinary symptoms when a horseshoe kidney and an enlarged, right cystic ovary were discovered. The radiographic appearance of the ovary was considered consistent with a benign cystic teratoma. No other genitourinary tract developmental anomalies were noted. There was no history of PID or endometriosis and sexual activity was denied. The b-hCG was negative. No masses were palpated on abdominal or pelvic examinations and the patient was asymptomatic at the time of laparoscopy. An enlarged right ovarian cystic mass was identified on laparoscopic examination. Additionally, three cystic structures were seen in the cul de sac, ranging from 1 cm to 2 cm in greatest diameter. Two cysts were connected by thin, opaque pedicles to the anterior pelvic peritoneum and extended into the cul de sac. The cyst walls were smooth and shiny and were opaque in areas adjacent to the pedicles (Fig. 4A, B). Two cysts ruptured during resection to reveal clear, serous fluid and the third cyst appeared recently ruptured. Pathology Macroscopic Findings. A total of 12 cysts were identified and all were resected laparoscopically. Eleven ruptured during resection and one ruptured preoperatively, rendering gross descriptions of intact cysts based on intraoperative findings of one surgeon (L.S.A.). These finding were complemented by the pathologists’ descriptions of the resected specimens. Each patient had multiple cysts (mean, 3 cysts/patient; range, 2e4 cysts/patient). The sizes ranged from 1 cm to 7 cm in greatest dimension. Except for one case where some cysts were partially opaque, the
44
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
Fig. 3. Case 3. (A) Pelvic CT. Complex cystic lesion with dense peripheral enhancement and thin-walled loculations, corresponding intraoperatively to peritoneal inclusion cysts, is indicated by an arrow. (B) Peritoneal inclusion cyst and thin pedicle, indicated by an arrow, is adherent to the cul de sac peritoneum.
cysts were orange-tan, thin-walled, and translucent. All were filled with clear, serous fluid and none contained gelatinous or hemorrhagic fluid. The outer wall surfaces were shiny and smooth and the inner linings were free of papillary excrescences. Except in one case, all were freely movable and nonadherent to the serosal surfaces of pelvic or abdominal structures. There was no evidence of solid, fibrotic areas, necrosis, or hemorrhage. Other procedures performed at the time of laparoscopy included adhesion lyses (three cases) and ovarian teratoma resection. Microscopic Findings. The microscopic architecture from all four cases was similar and conformed to the
previously described criteria (Fig. 5A). Mild to moderate reactive changes were occasionally identified and the septa were slightly expanded by fibrosis and chronic inflammatory infiltrate in only one case. No mesothelial-associated changes, previously described in children and adult females, were identified.7,9,10,15,16 Smooth muscle was conspicuously absent. Immunohistochemistry. The immunostaining profile was similar in all four cases. The cytoplasm of mesothelial cells revealed strong positive immunoreactivity for calretinin and cytokeratin 5/6 antibodies, negative immunoreactivity for B72.3 and except in one case, negative immunoreactivity for CEA
Fig. 4. Case 4. (A & B) Two peritoneal inclusion cysts extended from different sites of the anterior pelvic peritoneum by thin, tan-opaque pedicles, which are designated by arrows, to reside in the cul de sac.
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
45
Fig. 5. (A) Variably-sized cystic spaces are lined by mesothelial cells, some with a hobnail appearance, and are separated by thin fibrovascular septa (H&E 250). Mesothelial cells show strong positive immunoreactivity for calretinin (B) and cytokeratin 5/6 antibodies (C) and negative staining for CEA (D) and B72.3 (E) (400).
(Fig. 5BeE). Focal, rare positive immunoreactivity to CEA was identified in one case (case 3). Discussion The four patients included in this report represent the largest case series of peritoneal inclusion cysts described in the young female adolescent population. Indeed, over the last 20 years, a total of four cases have been individually cited in three case studies, with the clinical and pathological features partially described.7,9,10 The major clinical characteristics of the four adolescents reported in this series together with data retrieved from the four previously reported cases are summarized in Table 1. The patients in our series were all nulliparous adolescents of Caucasian ancestry. Of the previous reports, one patient was nulliparous and another, parous. Data regarding parity were not recorded in two cases.7,10 One of the four was Caucasian and definitive ancestries were not recorded for the remaining three.7 For our group, the mean age at diagnosis was 13.8 years (range, 11e16 years) and represents a younger population subset than that recorded in the previous reports (mean, 17 years; range 15e18 years).7,9,10 Pelvic pain was the most common presenting symptom in our series, recorded in three of the four, and was similar to (lower) abdominal pain recorded in three of four patients in the previous three series. Both our series and the previous reported cases had one asymptomatic patient with each evaluated for an
unrelated condition and peritoneal inclusion cysts were an incidental finding (case 4 and Sawh).10 Pain duration ranged from 4 days to several months in our group and this was paralleled in the previous reports (not shown). Acute presentations, occasionally simulating appendicitis, have been described in adult females diagnosed with peritoneal inclusion cysts and were also experienced both in our series and in previous reports.4,7e10,19 Indeed, one of our patients presented acutely with severe pelvic pain, fever, and a hypotensive event (case 3), while another elicited abdominal tenderness and guarding without rebound tenderness (case 1). Of the previous reports, a 15-year-old presented with acute-onset pain and peritoneal signs.7 For all the patients with acute presentations, peritoneal inclusion cysts were the major intraoperative finding. In the McFadden and Clement report, a ruptured peritoneal inclusion cyst was considered the source of hemoperitoneum and multiple cysts were adherent to the ovarian surfaces.7 No palpable masses were detected in any of our four subjects or in three of the four previously reported cases.7,9,10 Radiographic imaging studies (ultrasound, CT or both) provided evidence of a pelvic mass or lesion in three of four cases in our series. This finding is at variance with reports of adult females in which a palpable mass is often present.7,9,10 Of interest, two patients in our series also were discovered to have incidental renal developmental anomalies. The histories of PID and endometriosis were all negative in our series and in at least one previous report, a negative history for these disorders was
Abbreviations: Appy. 5 appendectomy; CT 5 Computed Tomography; Dx 5 diagnosis; HS 5 hydrosalpinx, L. 5 left; Mo. 5 month; NED 5 No Evidence of Disease; NR 5 Not Recorded; Nullip. 5 nulliparous; PG 5 Pregnancy; PIC 5 Peritoneal Inclusion Cyst; PID 5 Pelvic Inflammatory Disease; Rec. 5 recurrences; Res. 5 resection; RO 5 Right Oophorectomy; US 5 ultrasound.
NED at 83mo 5 Rec. until 253mo; NED at age 39yrs PIC PIC NR No No No NR No Yes NR NR NR 17 18
Constipation mass Abdominal pain
Lost to follow-up Ruptured Ectopic PG, PIC No NR NR No Asymptomatic Parous
Nullip 15
18
Sawh (2003) 1 Ross (1989) 1 2
NED at 36mo PIC, Hemo-Peritoneum No No No No
No No No No On US, CT On CT Pelvic Pain, fever Asymptomatic Nullip Nullip
3 4 McFadden (1986) 1
16 15
Acute abdominal pain, peritonitis
Lost to follow-up NED at 8mo PIC, HS Adhesions Mature Teratoma, PIC
PIC, Adhesions PIC, Adhesions
Appy RO. L. Ovarian wedge res Appy No No No No No On US No Pelvic Pain Pelvic Pain 11 13 Amesse (Present Study) 1 2
Nullip. Nullip
Post Op Dx Prior Surgery Endo metriosis PID Pelvic Mass Presentation Parity Age (Yrs) Author & Case
Table I. Clinical Features of Peritoneal Inclusion Cysts in Adolescent Females and Data Summary of Four Reported Cases
Pelvic pain; NED at 37 mo Pelvic pain; NED at 26 mo
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
Follow-up
46
recorded for one adolescent. While the collective data is at variance with previous reports of adult females where peritoneal inclusion cysts usually occur in background of PID and/or endometriosis, this observation is not unexpected.2,5e8 None of our patients were sexually active and were, in general, too young to have endometriosis and this may well have been true for three of four adolescents previously reported. With one exception, in our group there was a history of previous abdominal or pelvic surgery with durations between prior surgery and laparoscopy 7 months, 19 months, and 33 months for cases 1, 2 and 3, respectively. Appendectomy was the most common prior surgery (2/3, 67%) and the appendix was perforated in one patient. Another patient underwent laparotomy for ovarian torsion and two subsequent laparoscopies for recurrent ovarian cysts. A history of previous abdominal surgery in our series correlates with similar reports of adult women, but is at variance with the previous cases of adolescent females. Indeed, of the previous reports, three of four patients gave a negative history of prior surgery and it is likely that this finding may be related to the small sample size.2,5e10 Clinical follow-up data were obtained on six of eight adolescents: three from our series and three from previous reports. The mean follow-up period for our group was 23.7 months (range, 8 months to 37 months) and represented a shorter duration than that recorded for the previous four cases (mean, 124 months; range, 36 months to 253 months). Both in our group and the previous reports, one patient was lost to follow-up. Only one (1/6 5 17%) recurrence was reported and it was from one previous report. This observation suggests that local recurrences in female adolescents may be less likely than in adult females, in whom recurrences approach nearly 50%.3,9 For the single adolescent with local recurrence, the profile was similar to multiple recurrences reported in adults. Indeed, she experienced five recurrences up to 214 months post operatively until age 39 years at which time there was no evidence of disease.9 Two adolescents in our series still complained of pelvic pain, although less pronounced, after surgery. One of the two was subsequently diagnosed with depression, and receives antidepressant therapy. She also experienced a witnessed seizure one year post operatively, unrelated to the surgery. Ultrasound at 2 months post operatively revealed normal size ovaries in one of our cases and minimal free fluid in the cul de sac in two. There was no evidence of recurrences. All of our patients, as well as the four previously reported, were managed surgically for the stated indications. However, we recommend in young adolescents that treatment strategies be individualized until larger studies have been conducted and definitive
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
management guidelines have been established. Whether this entity represents a reactive response to injury (trauma, surgery) or a neoplasia has not been definitively determined and this limits our ability to accurately predict their behavior. However, data from our study and the other three series provides some insight into behavioral trends. The peritoneal cysts in this age group appear to follow a less aggressive course than that reported in adults. The cysts do not appear to parallel the waxing and waning of functional ovarian cysts, possibly related to the lowto-absent expression in cyst walls of estrogen and progesterone receptors.10 It is unknown whether the cysts over time can spontaneously regress or enlarge to potentially compress abdominal structures. Thus, in some cases, where peritoneal cysts have been discovered in the absence of pelvic pain and bladder or compressive symptoms, it may be advisable to follow the patient over time using transvaginal and/or transabdominal ultrasound or if necessary, CT scan. The major pathologic features of the peritoneal inclusion cysts described in this series together with data retrieved from four reported cases are summarized in Table 2. The cul de sac was the only anatomic location for all 12 cysts in our group and of the previous reports, the pelvis, cul de sac, ovarian surface and colon were all recorded.7,9,10 The cysts in our study were smaller, ranging from 1 cm to 7 cm, than the 3 cm to 19 cm range recorded in the previous series and were also smaller than those described in reports of children and adult females. In addition, the cysts in our group were neither large, confluent masses nor free floating.7e10,16,17 They were structurally uncomplicated, and except for one case, did not adhere to pelvic or abdominal viscera and
47
were uninvolved in coexisting adhesions. Moreover, they were not associated with complications such as hemoperitoneum or ovarian adherence as was previously reported in one adolescent.7 The presence of a well-formed pedicle identified in all 12 cysts in our series was unusual. This finding was not recorded in previous reports of female adolescents and has been rarely described as a structural component of peritoneal inclusion cysts occurring in other populations. In one rare description, Ross and coworkers in their series of 25 cases reported that a cyst was attached by a pedicle to the right adnexa, not the peritoneum as was the case in all our cases.9 It is possible that pedicles are a normal component of peritoneal inclusion cysts, but have been largely overlooked and thus, underreported. The microscopic architecture of our cysts was similar to previous reports, but none of the mesothelialassociated changes occasionally reported in adolescent females, children and adult females were identified.7,9,10,16,17 Only a trivial variation was identified in a specimen from a patient with a prior perforated appendix. The variation was characterized by mild to moderate reactive mesothelial changes and chronic inflammatory infiltrate with mild septal fibrotic expansion (case 3). Absent from all the cases was smooth muscle, distinguishing it from the similarappearing lymphangioma.1 A number of authors have contributed to defining the immunophenotype of peritoneal inclusion cysts and, together with electron microscopic studies, established the mesothelial origin of the cyst-lining cells.2,6,7,10,19 Mesothelial cells characteristically reveal strong positive immunoreactivity for calretinin and cytokeratin antibodies and negative staining for
Table 2. Pathologic Features of Peritoneal Inclusion Cysts in Adolescent Females and Data Summary of Four Reported Cases
Author & Case Amesse (Present 1 2 3 4 McFadden (1986) 1 Sawh (2003) 1 Ross (1989) 1 2
Location Study) Cul de Cul de Cul de Cul de
sac sac sac sac
Size Range (cm)
2-5 4-7 1.5-3.6 1-2
Number of Cysts
Cysts Attached to:
Micro:
Serosa
Adhesions
MMP
SM
3 2 4 3
No No Yes No
No No Yes No
-
-
Immunohistochemistry: A
Cal
CK
CEA
B72.3
-
þ þ þ þ
þ þ þ þ
þ* -
-
Surface, left ovary
6
multiple
Yes
No
NR
NR
NR
NR
þ
-
NR
Cul de sac; colon
6
2
NR
NR
þ
þ
-
þ
NR
NR
NR
pelvis pelvis
19 NR
multiple multiple
NR NR
NR NR
NR NR
NR NR
NR NR
NR NR
NR NR
NR NR
NR NR
Abbreviations: A 5 adenomatoid tumor-like patterns; Cal 5 calrenin; CK 5 cytokeratin; Micro 5 microscopic findings; MMP 5 mural mesothelial proliferations; NR 5 not recorded; SM 5 squamous metaplasia; þ 5 strong, positive immunreactivity; þ* 5 rare, focal positive immunoreactivity; - 5 negative immunoreactivity.
48
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
CEA and B72.3 antibodies. The immunostaining pattern in all our cases was similar and correlated with previous reports. One of our four cases displayed rare, focal positive immunoreactivity for the CEA antibody. This finding, while at variance with most reports, may represent a normal variation in the staining profile. Peritoneal inclusion cysts are uncommon lesions and of those reported, only a small percentage have undergone immunohistochemical studies. It is possible that some cysts, such as those identified in our series, may express focal positive immunoreactivity for CEA. Supporting this concept, a recent report described in a peritoneal inclusion cyst the presence of positive CEA immunostaining.20 Peritoneal inclusion cysts identified in young adolescent females share presenting symptoms and histories of previous abdominal surgeries similar to those reported in other female adolescents and adults. However, female adolescents may be less likely to present with a palpable mass and for this reason, radiographic studies such as ultrasound and CT scans are recommended. The cysts may also be less likely to arise in association with a history of PID and/or endometriosis. Moreover, local recurrences and associated complications reported in adult females appear to be less likely to occur. The cases in our series also differed morphologically from those previously reported by having a smaller cyst size, uncomplicated gross and microscopic appearances, the presence of a welldefined pedicle and general noninvolvement with adhesions and pelvic structures. References 1. Mennemeyer R, Smith M: Multicystic, peritoneal mesothelioma: a report with electron microscopy of a cases mimicking intra-abdominal cystic hygroma (lymphangioma.). Cancer 1979; 44:692 2. Moore JH Jr, Crum CP, Chandler JG, et al: Benign cystic mesothelioma. Cancer 1980; 45:2395 3. Katsube Y, Mukai K, Silverberg SG: Cystic mesothelioma of the peritoneum: a report of five cases and review of the literature. Cancer 1982; 50:1615 4. Schneider V, Partridge JR, Gutierrez F, et al: Benign cystic mesothelioma involving the female genital tract: report of four cases. Am J Obstet Gynecol 1983; 145:355 5. Carpenter HA, Lancaster JR, Lee RA: Multilocular cysts of the peritoneum. Mayo Clin Proc 1982; 57:634
6. Sienkowski IK, Russell AJ, Dilly SA, et al: Benign cystic mesothelioma: an electron microscopic and immunohistochemical study of two male patients. J Clin Pathol 1986; 39:440 7. McFadden DE, Clement PB: Peritoneal inclusion cysts with mural mesothelial proliferations: a clinicopathological analysis of six cases. Am J Surg Path 1986; 10:844 8. Weiss SW, Tavassoli FA: Multicystic mesothelioma. An analysis of pathologic findings and biologic behavior in 37 cases. Am J Surg Pathol 1988; 12:737 9. Ross MJ, Welch WR, Scully RE: Multilocular peritoneal inclusion cysts (so-called cystic mesotheliomas). Cancer 1989; 64:1336 10. Sawh R, Malpica A, Deavers MT, et al: Benign cystic mesothelioma of the peritoneum: a clinicopathologic study of 17 cases and immunohistochemical analysis of estrogen and progesterone receptor status. Hum Pathol 2003; 34: 369 11. Lascano EF, Villamayor RD, Llauro JL: Loose cysts of the peritoneal cavity. Ann Surg 1960; 152:836 12. Walker AR, Putnam TC: Omental, mesenteric, and retroperitoneal cysts: a clinical study of 33 new cases. Ann Surg 1973; 178:13 13. Safioleas M, Constantinos K, Michael S, et al: Benign multicystic peritoneal mesothelioma: a case report and review of the literature. World J Gastroenterol 2006; 12: 5739 14. Hanukoglu A, Gewurtz G, Zaidel L, et al: Benign cystic mesothelioma of the peritoneum: the occurrence of an adult entity in a child. Med Pediatr Oncol 1992; 20:169 15. Niggli FK, Gray TJ, Raafat F, et al: Spectrum of peritoneal mesothelioma in childhood: clinical and histopathogical features including DNA cytometry. Pediatr Hematol Oncol 1994; 11:399 16. McCullagh M, Keen C, Dykes E: Cystic mesothelioma of the peritoneum: a rare case of ‘‘ascites’’ in children. J Pediatr Surg 1994; 29:1205 17. Gonzalez-Crussi F, Sotelo-Avila C, deMello DE: Primary peritoneal, omental, and mesenteric tumors in childhood. Semin Diagn Pathol 1986; 3:122 18. Amesse LS, Moulton R, Zhang YM, et al: Expression of HOX gene products in normal and abnormal trophoblast tissue. Gynecol Oncol 2003; 90:512 19. Urbanczyk K, Skotniczny K, Kucinski J, et al: Mesothelial inclusion cysts (so-called benign cystic mesothelioma)— a clinicopathological analysis of six cases. Pol J Pathology 2005; 56:81 20. Holtzman RN, Heymann AD, Bordone F, et al: Carbohydrate antigen 19-9 and carcinoembryonic antigen immunostaining in benign multicystic mesothelioma of the peritoneum. Arch Pathol Lab Med 2001; 125:944
Original Studies Peritoneal Inclusion Cysts in Adolescent Females: A Clinicopathological Characterization of Four Cases Lawrence S. Amesse, MD, PhD, HCLD1, Paul Gibbs, MD2, John Hardy, MD1, Kimberly R. Jones1, and Teresa Pfaff-Amesse, MD1 1
Section of Pediatric and Adolescent Gynecology, Department of Obstetrics and Gynecology, Wright State University Boonshoft School of Medicine; 2Department of Pathology, Miami Valley Hospital, Dayton, Ohio, USA
Abstract. Study Objective: To identify adolescent females with peritoneal inclusion cysts and characterize the clinicopathologic features. Design: Observational and chart review along with immunohistochemical studies. Setting: University pediatric and adolescent clinic. Results: Medical records of all subjects, ages 10e18 years, diagnosed with peritoneal inclusion cysts over a 4-year period were retrospectively reviewed. Four patients, ages 11e16 years (mean, 13.8 yrs) were identified. Pelvic pain was the most common presenting symptom. No palpable abdominal or pelvic masses were detected. However, pelvic lesions were identified by radiographic studies in three of the four patients. Half experienced tenderness on examination. With one exception, all had a prior history of abdominal surgery. Twelve peritoneal inclusion cysts were identified, ranging from 1 cm to 7 cm in greatest diameter. Most were uninvolved in coexisting adhesions and non-adherent to pelvic or abdominal structures. Each had a well-defined pedicle connection to the peritoneum. No associated complications were identified. Their appearance conformed to established morphologic and immunohistochemical criteria, although accompanying mesothelial-associated changes occasionally reported in other populations were not detected. No recurrences were recorded. Conclusion: Young female adolescents with peritoneal inclusion cysts share presenting symptoms and histories of previous abdominal surgery similar to those reported in older female adolescents and adults. A palpable mass may not be detected on examination, but can often be identified using radiographic studies. Our cases differ from previous reports by smaller cyst size, presence of a pedicle, and uncomplicated gross and microscopic appearances. Additionally, local recurrences and associated complications occurred less than reported in adults.
Key Words. Peritoneal inclusion cysts—Adolescent females—Benign cystic mesothelioma—Multicystic mesothelioma—Inflammatory cysts of the peritoneum
Introduction
Address corsrespondence to: Lawrence S. Amesse, MD, PhD, Department of Obstetrics and Gynecology, Wright State University, Boonshoft School of Medicine, 128 E. Apple Street, Suite 3800 CHE, Dayton, Ohio 45409-2793.; E-mail: [email protected]
Peritoneal inclusion cysts are unusual lesions that usually occur in the pelvis of reproductive-age women. Although benign, local recurrences are common, often requiring repeated surgeries.1e9 The average age at diagnosis is approximately 32 years, with reported ages ranging from 17 to 61 years.9,10 In adult females, there is often a prior history of abdominal surgery, pelvic inflammatory disease (PID) or endometriosis.7e10 The most common presenting symptom is lower abdominal or pelvic pain. In some cases, a palpable mass can be detected. The cysts are often multiple, ranging from 1 cm to O20 cm in greatest diameter, with some forming confluent masses that fill the pelvis.11,12 They often adhere to pelvic and abdominal structures, yet some are free-floating in the peritoneum.4,7e9 Some experts consider these lesions a true neoplasm, while others advocate a reactive process. This dichotomy in pathogenesis is reflected by the various terms used to designate them, including benign cystic mesothelioma, multicystic mesothelioma, and inflammatory cysts of the peritoneum.8,9 Although this entity is predominantly diagnosed in reproductive-age females, well-documented cases of peritoneal inclusion cysts have been described in menopausal women, men, and preadolescent children.2,5,13e17 Reports of these cysts occurring in adolescent females are rare. Indeed, only four cases have been reported in the last 20 years.7,9,10 We describe our experience with four female adolescents diagnosed with peritoneal inclusion cysts, characterize
Ó 2009 North American Society for Pediatric and Adolescent Gynecology Published by Elsevier Inc.
1083-3188/09/$34.00 doi:10.1016/j.jpag.2008.02.003
42
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
the clinicopathologic features, and include a review of the literature. Methods The medical records at the Pediatric/Adolescent Section, Department of Obstetrics and Gynecology, at Miami Valley Hospital, and the Gynecology Service at Children’s Hospital Medical Center were searched for all patients, ages 10 to 18 years, diagnosed with peritoneal inclusion cysts between January 2002 and December 2006. Four patients were identified and imaging studies, pathology reports and histology slides were reviewed. Paraffin blocks were retrieved from archives. Follow-up data were obtained in three cases from the medical records and office visits. Hematoxylin and eosin-stained glass slides from each case were examined. All cases fulfilling the following standard histological criteria were included: uni- or multilocular cysts; single layer of mesothelial cells; fibrovascular septa; and no evidence of smooth muscle. The slides were also examined for the following mesothelial-associated changes and growth patterns occasionally described in previous reports: mural mesothelial proliferations, adenomatoid tumor-like patterns, squamous metaplasia, glands, nests, small papillae or cribiform pattern, xanthomatous changes, endometriosis and cytologic atypia.7e10 Representative sections from each case were selected for immunohistochemical studies to confirm the mesothelial cell origin. Immunostaining was performed as previously described with modified label avidin-biotin peroxidase complex method and Dako Cytomation Autostainer (Dako Cytomation Corp., Carpinteria, CA) the only modifications.18 The following mouse primary monoclonal IgG1 antibodies and their respective dilutions were used: cytokeratin (CK) 5/6 (1:1100) (Biocare Medical, Clone CK5/ 6.007, Concord, CA); carcinoembryonic antigen (CEA) (1:400) and CD 175 or B72.3 (1:100) (Dako Cytomation Corp., Clone II-7 and Clone HB-STn1, respectively, Carpinteria, CA). The rabbit polyclonal antibody to calretinin (1:100) (Zymed Laboratories, Clones DC8, San Francisco, CA) was also used as a primary antibody. Results Clinical Findings Case 1. L.M. was an 11-year-old nulliparous adolescent with a last menstrual period 6 weeks prior to presentation who complained of pelvic pain, refractory to medical therapy, of 4 months duration. The patient was 7 months status post laparoscopic appendectomy. Gastrointestinal and genitourinary symptoms as well as sexual activity were denied. The medical history
was negative for PID and endometriosis. Physical examination revealed moderate abdominal tenderness, mild guarding, and absent rebound tenderness. Transabdominal ultrasound of the pelvis revealed a 19- mm cystic mass within an enlarged right ovary, considered consistent with a hemorrhagic ovarian cyst. A complex cystic 5.5 cm 2.2 cm mass was also detected in the cul de sac (Fig. 1A). Extensive adhesions were identified on laparoscopy. Three multiloculated cysts were found in the cul de sac and each was connected to the peritoneum by a pedicle. They did not adhere to pelvic structures and were uninvolved with adhesions. The largest measured 4 cm 5 cm and was attached to the anterior pelvic wall peritoneum, with the cyst proper extending into the cul de sac, adjacent to the ovaries. Budding off the superior aspect of the same pedicle was a smaller, similar appearing 2 cm 3 cm cyst. The pedicle of the third cyst, which measured 3 cm 5 cm, originated from the cul de sac peritoneum. The cysts were translucent and filled with clear serous fluid (Fig. 1B, C). After adhesion lyses, the cysts were removed and sent to pathology.
Case 2. A.K. was a 13-year-old menarchal, nulligravida referred for evaluation of pelvic pain, refractory to medical management, of several months duration. Nineteen months prior to referral, she underwent a right oophorectomy and left ovarian wedge resection for ovarian torsion and cysts, respectively. There was no history of PID or endometriosis. Pelvic examination revealed minimal lower abdominal tenderness with no palpable masses. The transabdominal pelvic ultrasound was unremarkable. Laparoscopic examination revealed extensive pelvic, omental and abdominal adhesions. Two multiloculated cysts (range, 4 cme7 cm in greatest diameter) were identified in the cul de sac, adjacent to the ovaries (Fig. 2). They were uninvolved with adhesions and did not adhere to the surface of the ovaries, tubes, uterus or other structures. The initial impression was that they were paratubal in origin. However, upon exploration and dissection, they were discovered to have pedicle attachments to different sites of the anterior pelvic peritoneum. They were translucent, contained clear, serous fluid, and collapsed upon resection.
Case 3. L.H. was a 16-year-old, nulliparous teenager referred for evaluation of pelvic pain and fever of 4 days duration, unresponsive to antibiotic therapy, with an episode of acute hypotension. She was 2 years, 9 months status post open appendectomy for a perforated appendix. The history of PID and endometriosis
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
43
Fig. 1. Case 1. (A) Transabdominal ultrasound of the pelvis. Peritoneal inclusion cysts, located in the cul de sac, are designated by an arrow. (B, C) In situ findings of two peritoneal inclusion cysts. The pedicle connection to the peritoneum is designated by an arrow in B.
was negative. Sexual activity was denied and the bhCG was negative. A transabdominal ultrasound of the pelvis and kidneys identified a 5 cm 2 cm heterogeneous, complex fluid-filled cystic lesion, considered consistent with a tuboovarian abscess, abutting the left ovary along the posterior aspect of the uterus. An incidental right extrarenal pelvis was also identified. No additional developmental anomalies were detected. Similar findings were identified on the pelvic computed tomography (CT) (Fig. 3A). The pelvis was encased in extensive fibrous adhesions, forming a ‘‘frozen pelvis’’ with omental and bowel adhesions also evident on laparoscopic examination. Bilateral hydrosalpinx and tubal occlusions were identified, but there was no evidence of a tuboovarian abscess. Four cysts, ranging from 1.5 cm 2 cm to 3.2 cm 3.6 cm in greatest dimension, were identified in the cul de sac and were involved in adhesions. Some adhered to the ovarian surfaces and others, to the uterine and tubal serosa. The initial impression was that they represented benign ovarian
Fig. 2. Case 2. Multiloculated peritoneal inclusion cyst. The arrow indicates the inferior aspect of the pedicle, with the translucent cyst apparent.
cysts or florid cystic endosalpingiosis. However, upon dissection, all originated at the cul de sac peritoneum where they were connected by a pedicle (Fig. 3B). Case 4. J.P. was 15-year-old nulliparous, menarchal adolescent referred for resection of a cystic ovarian mass. The patient was evaluated by CT scan for recurrent urinary symptoms when a horseshoe kidney and an enlarged, right cystic ovary were discovered. The radiographic appearance of the ovary was considered consistent with a benign cystic teratoma. No other genitourinary tract developmental anomalies were noted. There was no history of PID or endometriosis and sexual activity was denied. The b-hCG was negative. No masses were palpated on abdominal or pelvic examinations and the patient was asymptomatic at the time of laparoscopy. An enlarged right ovarian cystic mass was identified on laparoscopic examination. Additionally, three cystic structures were seen in the cul de sac, ranging from 1 cm to 2 cm in greatest diameter. Two cysts were connected by thin, opaque pedicles to the anterior pelvic peritoneum and extended into the cul de sac. The cyst walls were smooth and shiny and were opaque in areas adjacent to the pedicles (Fig. 4A, B). Two cysts ruptured during resection to reveal clear, serous fluid and the third cyst appeared recently ruptured. Pathology Macroscopic Findings. A total of 12 cysts were identified and all were resected laparoscopically. Eleven ruptured during resection and one ruptured preoperatively, rendering gross descriptions of intact cysts based on intraoperative findings of one surgeon (L.S.A.). These finding were complemented by the pathologists’ descriptions of the resected specimens. Each patient had multiple cysts (mean, 3 cysts/patient; range, 2e4 cysts/patient). The sizes ranged from 1 cm to 7 cm in greatest dimension. Except for one case where some cysts were partially opaque, the
44
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
Fig. 3. Case 3. (A) Pelvic CT. Complex cystic lesion with dense peripheral enhancement and thin-walled loculations, corresponding intraoperatively to peritoneal inclusion cysts, is indicated by an arrow. (B) Peritoneal inclusion cyst and thin pedicle, indicated by an arrow, is adherent to the cul de sac peritoneum.
cysts were orange-tan, thin-walled, and translucent. All were filled with clear, serous fluid and none contained gelatinous or hemorrhagic fluid. The outer wall surfaces were shiny and smooth and the inner linings were free of papillary excrescences. Except in one case, all were freely movable and nonadherent to the serosal surfaces of pelvic or abdominal structures. There was no evidence of solid, fibrotic areas, necrosis, or hemorrhage. Other procedures performed at the time of laparoscopy included adhesion lyses (three cases) and ovarian teratoma resection. Microscopic Findings. The microscopic architecture from all four cases was similar and conformed to the
previously described criteria (Fig. 5A). Mild to moderate reactive changes were occasionally identified and the septa were slightly expanded by fibrosis and chronic inflammatory infiltrate in only one case. No mesothelial-associated changes, previously described in children and adult females, were identified.7,9,10,15,16 Smooth muscle was conspicuously absent. Immunohistochemistry. The immunostaining profile was similar in all four cases. The cytoplasm of mesothelial cells revealed strong positive immunoreactivity for calretinin and cytokeratin 5/6 antibodies, negative immunoreactivity for B72.3 and except in one case, negative immunoreactivity for CEA
Fig. 4. Case 4. (A & B) Two peritoneal inclusion cysts extended from different sites of the anterior pelvic peritoneum by thin, tan-opaque pedicles, which are designated by arrows, to reside in the cul de sac.
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
45
Fig. 5. (A) Variably-sized cystic spaces are lined by mesothelial cells, some with a hobnail appearance, and are separated by thin fibrovascular septa (H&E 250). Mesothelial cells show strong positive immunoreactivity for calretinin (B) and cytokeratin 5/6 antibodies (C) and negative staining for CEA (D) and B72.3 (E) (400).
(Fig. 5BeE). Focal, rare positive immunoreactivity to CEA was identified in one case (case 3). Discussion The four patients included in this report represent the largest case series of peritoneal inclusion cysts described in the young female adolescent population. Indeed, over the last 20 years, a total of four cases have been individually cited in three case studies, with the clinical and pathological features partially described.7,9,10 The major clinical characteristics of the four adolescents reported in this series together with data retrieved from the four previously reported cases are summarized in Table 1. The patients in our series were all nulliparous adolescents of Caucasian ancestry. Of the previous reports, one patient was nulliparous and another, parous. Data regarding parity were not recorded in two cases.7,10 One of the four was Caucasian and definitive ancestries were not recorded for the remaining three.7 For our group, the mean age at diagnosis was 13.8 years (range, 11e16 years) and represents a younger population subset than that recorded in the previous reports (mean, 17 years; range 15e18 years).7,9,10 Pelvic pain was the most common presenting symptom in our series, recorded in three of the four, and was similar to (lower) abdominal pain recorded in three of four patients in the previous three series. Both our series and the previous reported cases had one asymptomatic patient with each evaluated for an
unrelated condition and peritoneal inclusion cysts were an incidental finding (case 4 and Sawh).10 Pain duration ranged from 4 days to several months in our group and this was paralleled in the previous reports (not shown). Acute presentations, occasionally simulating appendicitis, have been described in adult females diagnosed with peritoneal inclusion cysts and were also experienced both in our series and in previous reports.4,7e10,19 Indeed, one of our patients presented acutely with severe pelvic pain, fever, and a hypotensive event (case 3), while another elicited abdominal tenderness and guarding without rebound tenderness (case 1). Of the previous reports, a 15-year-old presented with acute-onset pain and peritoneal signs.7 For all the patients with acute presentations, peritoneal inclusion cysts were the major intraoperative finding. In the McFadden and Clement report, a ruptured peritoneal inclusion cyst was considered the source of hemoperitoneum and multiple cysts were adherent to the ovarian surfaces.7 No palpable masses were detected in any of our four subjects or in three of the four previously reported cases.7,9,10 Radiographic imaging studies (ultrasound, CT or both) provided evidence of a pelvic mass or lesion in three of four cases in our series. This finding is at variance with reports of adult females in which a palpable mass is often present.7,9,10 Of interest, two patients in our series also were discovered to have incidental renal developmental anomalies. The histories of PID and endometriosis were all negative in our series and in at least one previous report, a negative history for these disorders was
Abbreviations: Appy. 5 appendectomy; CT 5 Computed Tomography; Dx 5 diagnosis; HS 5 hydrosalpinx, L. 5 left; Mo. 5 month; NED 5 No Evidence of Disease; NR 5 Not Recorded; Nullip. 5 nulliparous; PG 5 Pregnancy; PIC 5 Peritoneal Inclusion Cyst; PID 5 Pelvic Inflammatory Disease; Rec. 5 recurrences; Res. 5 resection; RO 5 Right Oophorectomy; US 5 ultrasound.
NED at 83mo 5 Rec. until 253mo; NED at age 39yrs PIC PIC NR No No No NR No Yes NR NR NR 17 18
Constipation mass Abdominal pain
Lost to follow-up Ruptured Ectopic PG, PIC No NR NR No Asymptomatic Parous
Nullip 15
18
Sawh (2003) 1 Ross (1989) 1 2
NED at 36mo PIC, Hemo-Peritoneum No No No No
No No No No On US, CT On CT Pelvic Pain, fever Asymptomatic Nullip Nullip
3 4 McFadden (1986) 1
16 15
Acute abdominal pain, peritonitis
Lost to follow-up NED at 8mo PIC, HS Adhesions Mature Teratoma, PIC
PIC, Adhesions PIC, Adhesions
Appy RO. L. Ovarian wedge res Appy No No No No No On US No Pelvic Pain Pelvic Pain 11 13 Amesse (Present Study) 1 2
Nullip. Nullip
Post Op Dx Prior Surgery Endo metriosis PID Pelvic Mass Presentation Parity Age (Yrs) Author & Case
Table I. Clinical Features of Peritoneal Inclusion Cysts in Adolescent Females and Data Summary of Four Reported Cases
Pelvic pain; NED at 37 mo Pelvic pain; NED at 26 mo
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
Follow-up
46
recorded for one adolescent. While the collective data is at variance with previous reports of adult females where peritoneal inclusion cysts usually occur in background of PID and/or endometriosis, this observation is not unexpected.2,5e8 None of our patients were sexually active and were, in general, too young to have endometriosis and this may well have been true for three of four adolescents previously reported. With one exception, in our group there was a history of previous abdominal or pelvic surgery with durations between prior surgery and laparoscopy 7 months, 19 months, and 33 months for cases 1, 2 and 3, respectively. Appendectomy was the most common prior surgery (2/3, 67%) and the appendix was perforated in one patient. Another patient underwent laparotomy for ovarian torsion and two subsequent laparoscopies for recurrent ovarian cysts. A history of previous abdominal surgery in our series correlates with similar reports of adult women, but is at variance with the previous cases of adolescent females. Indeed, of the previous reports, three of four patients gave a negative history of prior surgery and it is likely that this finding may be related to the small sample size.2,5e10 Clinical follow-up data were obtained on six of eight adolescents: three from our series and three from previous reports. The mean follow-up period for our group was 23.7 months (range, 8 months to 37 months) and represented a shorter duration than that recorded for the previous four cases (mean, 124 months; range, 36 months to 253 months). Both in our group and the previous reports, one patient was lost to follow-up. Only one (1/6 5 17%) recurrence was reported and it was from one previous report. This observation suggests that local recurrences in female adolescents may be less likely than in adult females, in whom recurrences approach nearly 50%.3,9 For the single adolescent with local recurrence, the profile was similar to multiple recurrences reported in adults. Indeed, she experienced five recurrences up to 214 months post operatively until age 39 years at which time there was no evidence of disease.9 Two adolescents in our series still complained of pelvic pain, although less pronounced, after surgery. One of the two was subsequently diagnosed with depression, and receives antidepressant therapy. She also experienced a witnessed seizure one year post operatively, unrelated to the surgery. Ultrasound at 2 months post operatively revealed normal size ovaries in one of our cases and minimal free fluid in the cul de sac in two. There was no evidence of recurrences. All of our patients, as well as the four previously reported, were managed surgically for the stated indications. However, we recommend in young adolescents that treatment strategies be individualized until larger studies have been conducted and definitive
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
management guidelines have been established. Whether this entity represents a reactive response to injury (trauma, surgery) or a neoplasia has not been definitively determined and this limits our ability to accurately predict their behavior. However, data from our study and the other three series provides some insight into behavioral trends. The peritoneal cysts in this age group appear to follow a less aggressive course than that reported in adults. The cysts do not appear to parallel the waxing and waning of functional ovarian cysts, possibly related to the lowto-absent expression in cyst walls of estrogen and progesterone receptors.10 It is unknown whether the cysts over time can spontaneously regress or enlarge to potentially compress abdominal structures. Thus, in some cases, where peritoneal cysts have been discovered in the absence of pelvic pain and bladder or compressive symptoms, it may be advisable to follow the patient over time using transvaginal and/or transabdominal ultrasound or if necessary, CT scan. The major pathologic features of the peritoneal inclusion cysts described in this series together with data retrieved from four reported cases are summarized in Table 2. The cul de sac was the only anatomic location for all 12 cysts in our group and of the previous reports, the pelvis, cul de sac, ovarian surface and colon were all recorded.7,9,10 The cysts in our study were smaller, ranging from 1 cm to 7 cm, than the 3 cm to 19 cm range recorded in the previous series and were also smaller than those described in reports of children and adult females. In addition, the cysts in our group were neither large, confluent masses nor free floating.7e10,16,17 They were structurally uncomplicated, and except for one case, did not adhere to pelvic or abdominal viscera and
47
were uninvolved in coexisting adhesions. Moreover, they were not associated with complications such as hemoperitoneum or ovarian adherence as was previously reported in one adolescent.7 The presence of a well-formed pedicle identified in all 12 cysts in our series was unusual. This finding was not recorded in previous reports of female adolescents and has been rarely described as a structural component of peritoneal inclusion cysts occurring in other populations. In one rare description, Ross and coworkers in their series of 25 cases reported that a cyst was attached by a pedicle to the right adnexa, not the peritoneum as was the case in all our cases.9 It is possible that pedicles are a normal component of peritoneal inclusion cysts, but have been largely overlooked and thus, underreported. The microscopic architecture of our cysts was similar to previous reports, but none of the mesothelialassociated changes occasionally reported in adolescent females, children and adult females were identified.7,9,10,16,17 Only a trivial variation was identified in a specimen from a patient with a prior perforated appendix. The variation was characterized by mild to moderate reactive mesothelial changes and chronic inflammatory infiltrate with mild septal fibrotic expansion (case 3). Absent from all the cases was smooth muscle, distinguishing it from the similarappearing lymphangioma.1 A number of authors have contributed to defining the immunophenotype of peritoneal inclusion cysts and, together with electron microscopic studies, established the mesothelial origin of the cyst-lining cells.2,6,7,10,19 Mesothelial cells characteristically reveal strong positive immunoreactivity for calretinin and cytokeratin antibodies and negative staining for
Table 2. Pathologic Features of Peritoneal Inclusion Cysts in Adolescent Females and Data Summary of Four Reported Cases
Author & Case Amesse (Present 1 2 3 4 McFadden (1986) 1 Sawh (2003) 1 Ross (1989) 1 2
Location Study) Cul de Cul de Cul de Cul de
sac sac sac sac
Size Range (cm)
2-5 4-7 1.5-3.6 1-2
Number of Cysts
Cysts Attached to:
Micro:
Serosa
Adhesions
MMP
SM
3 2 4 3
No No Yes No
No No Yes No
-
-
Immunohistochemistry: A
Cal
CK
CEA
B72.3
-
þ þ þ þ
þ þ þ þ
þ* -
-
Surface, left ovary
6
multiple
Yes
No
NR
NR
NR
NR
þ
-
NR
Cul de sac; colon
6
2
NR
NR
þ
þ
-
þ
NR
NR
NR
pelvis pelvis
19 NR
multiple multiple
NR NR
NR NR
NR NR
NR NR
NR NR
NR NR
NR NR
NR NR
NR NR
Abbreviations: A 5 adenomatoid tumor-like patterns; Cal 5 calrenin; CK 5 cytokeratin; Micro 5 microscopic findings; MMP 5 mural mesothelial proliferations; NR 5 not recorded; SM 5 squamous metaplasia; þ 5 strong, positive immunreactivity; þ* 5 rare, focal positive immunoreactivity; - 5 negative immunoreactivity.
48
Amesse et al: Peritoneal Inclusion Cysts in Adolescent Females
CEA and B72.3 antibodies. The immunostaining pattern in all our cases was similar and correlated with previous reports. One of our four cases displayed rare, focal positive immunoreactivity for the CEA antibody. This finding, while at variance with most reports, may represent a normal variation in the staining profile. Peritoneal inclusion cysts are uncommon lesions and of those reported, only a small percentage have undergone immunohistochemical studies. It is possible that some cysts, such as those identified in our series, may express focal positive immunoreactivity for CEA. Supporting this concept, a recent report described in a peritoneal inclusion cyst the presence of positive CEA immunostaining.20 Peritoneal inclusion cysts identified in young adolescent females share presenting symptoms and histories of previous abdominal surgeries similar to those reported in other female adolescents and adults. However, female adolescents may be less likely to present with a palpable mass and for this reason, radiographic studies such as ultrasound and CT scans are recommended. The cysts may also be less likely to arise in association with a history of PID and/or endometriosis. Moreover, local recurrences and associated complications reported in adult females appear to be less likely to occur. The cases in our series also differed morphologically from those previously reported by having a smaller cyst size, uncomplicated gross and microscopic appearances, the presence of a welldefined pedicle and general noninvolvement with adhesions and pelvic structures. References 1. Mennemeyer R, Smith M: Multicystic, peritoneal mesothelioma: a report with electron microscopy of a cases mimicking intra-abdominal cystic hygroma (lymphangioma.). Cancer 1979; 44:692 2. Moore JH Jr, Crum CP, Chandler JG, et al: Benign cystic mesothelioma. Cancer 1980; 45:2395 3. Katsube Y, Mukai K, Silverberg SG: Cystic mesothelioma of the peritoneum: a report of five cases and review of the literature. Cancer 1982; 50:1615 4. Schneider V, Partridge JR, Gutierrez F, et al: Benign cystic mesothelioma involving the female genital tract: report of four cases. Am J Obstet Gynecol 1983; 145:355 5. Carpenter HA, Lancaster JR, Lee RA: Multilocular cysts of the peritoneum. Mayo Clin Proc 1982; 57:634
6. Sienkowski IK, Russell AJ, Dilly SA, et al: Benign cystic mesothelioma: an electron microscopic and immunohistochemical study of two male patients. J Clin Pathol 1986; 39:440 7. McFadden DE, Clement PB: Peritoneal inclusion cysts with mural mesothelial proliferations: a clinicopathological analysis of six cases. Am J Surg Path 1986; 10:844 8. Weiss SW, Tavassoli FA: Multicystic mesothelioma. An analysis of pathologic findings and biologic behavior in 37 cases. Am J Surg Pathol 1988; 12:737 9. Ross MJ, Welch WR, Scully RE: Multilocular peritoneal inclusion cysts (so-called cystic mesotheliomas). Cancer 1989; 64:1336 10. Sawh R, Malpica A, Deavers MT, et al: Benign cystic mesothelioma of the peritoneum: a clinicopathologic study of 17 cases and immunohistochemical analysis of estrogen and progesterone receptor status. Hum Pathol 2003; 34: 369 11. Lascano EF, Villamayor RD, Llauro JL: Loose cysts of the peritoneal cavity. Ann Surg 1960; 152:836 12. Walker AR, Putnam TC: Omental, mesenteric, and retroperitoneal cysts: a clinical study of 33 new cases. Ann Surg 1973; 178:13 13. Safioleas M, Constantinos K, Michael S, et al: Benign multicystic peritoneal mesothelioma: a case report and review of the literature. World J Gastroenterol 2006; 12: 5739 14. Hanukoglu A, Gewurtz G, Zaidel L, et al: Benign cystic mesothelioma of the peritoneum: the occurrence of an adult entity in a child. Med Pediatr Oncol 1992; 20:169 15. Niggli FK, Gray TJ, Raafat F, et al: Spectrum of peritoneal mesothelioma in childhood: clinical and histopathogical features including DNA cytometry. Pediatr Hematol Oncol 1994; 11:399 16. McCullagh M, Keen C, Dykes E: Cystic mesothelioma of the peritoneum: a rare case of ‘‘ascites’’ in children. J Pediatr Surg 1994; 29:1205 17. Gonzalez-Crussi F, Sotelo-Avila C, deMello DE: Primary peritoneal, omental, and mesenteric tumors in childhood. Semin Diagn Pathol 1986; 3:122 18. Amesse LS, Moulton R, Zhang YM, et al: Expression of HOX gene products in normal and abnormal trophoblast tissue. Gynecol Oncol 2003; 90:512 19. Urbanczyk K, Skotniczny K, Kucinski J, et al: Mesothelial inclusion cysts (so-called benign cystic mesothelioma)— a clinicopathological analysis of six cases. Pol J Pathology 2005; 56:81 20. Holtzman RN, Heymann AD, Bordone F, et al: Carbohydrate antigen 19-9 and carcinoembryonic antigen immunostaining in benign multicystic mesothelioma of the peritoneum. Arch Pathol Lab Med 2001; 125:944