What is LPD?
"...the enigmatic disorder known as disseminated peritoneal leiomyomatosis. DPL is very rare condition in which "fibroid" tumorlets numbering from a handful to hundreds are scattered about the peritoneal surfaces and omentum in the abdominal cavity. The way that we think about DPL changed after [Quade] laboratory published about paper showing that DPL tumorlets are "metastatic" from a single tumor clone. Despite this uniclonal origin, in most cases, DPL behaves as a clinically benign process, with many cases presenting incidentally and the rest of cases presenting because of symptoms related to the mass effect of these many tumorlets. In a very small number of cases, DPL seems to "transform" into leiomyosarcoma, another uniclonal, but malignant smooth muscle tumor. Consequently, for most patients, chemotherapy has little effect and the side effects cause more harm than benefit. DPL, like uterine fibroids (benign smooth muscle tumors that we diagnose as leiomyomas), is composed of benign smooth muscle tumor cells that are hormonally sensitive, and reducing the level of estrogen and progesterone by GnRH agonists (e.g., Lupron) and oopherectomy seems to help, but these obviously leave the patient in a postmenopausal state, which has important implications for bone, heart, and reproductive health. A few cases of hormone-secreting ovarian tumors have been associated with DPL as well. If mass effect symptoms are present, debulking surgery helps as long as the procedure is through and that the microscopic tumorlets don't grow back.
...patients with DPL should see a gynecologic oncologist (a doctor trained in the surgical management of tumors of the female genital tract), preferably one who practice in a university setting as they will be more likely to have managed a case or two. Unfortunately, there is no one out there that has taken care of large numbers of DPL patients. In New York, I would consider going to the Memorial-Sloane Kettering Cancer Center. Here at [Brigham and Women’s Hospital ], I would recommend seeing Dr. Mike Muto or Dr. Ross Berkowitz (or another member of their group)."
"Leiomyomatosis peritonealis disseminata (LPD), also known as diffuse peritoneal leiomyomatosis, is a rare disease in which multiple smooth muscle or smooth muscle-like nodules develop subperitoneally in any part of the abdominal cavity [1].
These nodules, though histologically benign, cannot be distinguished macroscopically from peritoneal carcinomatosis.
The aetiology is thought to be smooth muscle metaplasia of the subperitoneal mesenchyme [2]. About 100 documented cases were found in the English language literature; LPD patients are mainly females of reproductive age [3], and only rarely have cases affecting men been reported [4,5].
The condition is associated with high levels of exogenous and endogenous female gonadal steroids (e.g. pregnancy, prolonged exposure to oral contraceptives and/or combined hormonal replacement therapy, granulomatous cell tumours of the ovary) [4,6], indicating that oestrogens and progestins play an important role in the pathogenesis of LPD as they do in leiomyomata uteri.
Most LPD cases are clinically benign, and in some instances the lesions may partially or completely regress [5,7]. Alternatively, LPD may progress, recur or (rarely) undergo malignant transformation [8].
LPD is most common in women of reproductive age. More than half of all patients are pregnant or taking oral contraceptives at the time of diagnosis [14].
Quade et al. showed (in 1997) that LPD has molecular-genetic and cytogenetic features suggesting that individual tumourlets are monoclonal, with a pathogenesis similar to leiomyomata uteri. In LPD, the smooth muscle cells are influenced by oestrogens [7,15], and sex steroid receptors have been identified in nearly all cases [16]. LPD can be associated with other oestrogen-dependent diseases including endometriosis, ovarian clear cell carcinoma, endometrial carcinoma [17] and ovarian fibrothecoma [2]. Recently, two cases of development of LPD and ovarian Brenner tumour during tamoxifen [cancer drug] therapy have been reported [18-22].
Although LPD is most common in premenopausal women, cases have been reported in postmenopausal women using [23] or not using [13,24,25] hormone replacement therapy (HRT). The identification of luteinizing hormone (LH) receptors in LPD nodules from a postmenopausal woman suggests that the typical postmenopausal increase in LH levels might affect the pathogenesis of this condition [22].
Recently, familial occurrence of LPD has been described, showing an autosomal dominant model with varying degrees of penetrance [26].
Most patients with LPD present without specific symptoms and many documented cases of LPD have been discovered incidentally during surgery (caesarean section, laparotomy or laparoscopy). Sometimes patients may present with mostly non-specific symptoms, such as irregular, heavy uterine bleeding and pain or a mass in the lower abdomen [27], discomfort, urinary frequency (due to the effect of the mass on the bladder), gastrointestinal bleeding and peritonitis (following erosion of LPD implants in the bowel wall) [7,13,18,28]. Sometimes patients experience symptoms directly related to LPD: urosepsis secondary to obstruction of the ureters, and an acute abdomen due to ovarian torsion [29].
Sonographic and CT findings reported in the literature include non-specific, solid, and complex soft tissue masses that are often large and mimic a leiomyomatous uterus. In some cases, the masses grow in a fashion similar to that of normal uterine parenchyma, whereas others demonstrate heterogeneous enhancement. Diagnosis may be confused with peritoneal carcinomatosis if the masses are present diffusely throughout the abdomen and pelvis. Peritoneal carcinomatosis, however, is often associated with tumour cake, ascites and liver metastases, which have not been reported with LPD [29].
Magnetic Resonance (MR) findings include masses similar in signal intensity to skeletal muscle or uterine parenchyma, and when sarcomatous transformation occurs these are not significantly different from the features of benign implants. If the masses are located in the pelvis adjacent to the iliac vessels, they may be confused with lymphadenopathy [5,14,30-33]. Moreover, some multiple, pedunculated leiomyomas arising from the uterus may mimic LPD implants. Final diagnosis relies on histological examination [34] and immunohistochemical evaluation.
Sometimes, LPD may recur in patients taking HRT [13,24,25] even after hysterectomy and bilateral salpingo-oophorectomy [23], or in patients who have undergone in vitro fertilization [35]. Matthews and Speers reported a patient who died after a fourth recurrence of LPD and distant metastases 10 years after hysterectomy. Each recurrence seems to be more likely to produce morphological evidence of sarcoma [23].
Malignant transformation of LPD is uncommon and only ten cases have been documented in the English literature [8,29]. Of these, only three occurred in postmenopausal women (so seven cases of malignant transformation in premenopausal women)[29,36]. The interval between initial detection of LPD and the development of sarcoma varies from synchronous diagnosis to 8 years.
In most reports of malignant LPD, no history of oestrogen exposure was found. Bekkers hypothesized that LPD without exogenous or increased endogenous oestrogen exposure, and without expression of ER/PR by tumour cells, may represent a different entity carrying a higher risk of malignant transformation [3].
On the basis of these observations, we can affirm that no established guidelines exist regarding the management of LPD. However, therapy needs to be individualised according to the patient's age, hormonal and reproductive status and symptomatology. Different drugs (gonadotropin realising hormone agonist (GnRH agonist), megestrol acetate, danazol) have been considered in some cases but with poor results. If intestinal and bladder mass effect symptoms are prominent, a surgical approach is indicated [37]."
BMC Cancer. 2006; 6: 127.
Published online 2006 May 10. doi: 10.1186/1471-2407-6-127.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1481579
...patients with DPL should see a gynecologic oncologist (a doctor trained in the surgical management of tumors of the female genital tract), preferably one who practice in a university setting as they will be more likely to have managed a case or two. Unfortunately, there is no one out there that has taken care of large numbers of DPL patients. In New York, I would consider going to the Memorial-Sloane Kettering Cancer Center. Here at [Brigham and Women’s Hospital ], I would recommend seeing Dr. Mike Muto or Dr. Ross Berkowitz (or another member of their group)."
"Leiomyomatosis peritonealis disseminata (LPD), also known as diffuse peritoneal leiomyomatosis, is a rare disease in which multiple smooth muscle or smooth muscle-like nodules develop subperitoneally in any part of the abdominal cavity [1].
These nodules, though histologically benign, cannot be distinguished macroscopically from peritoneal carcinomatosis.
The aetiology is thought to be smooth muscle metaplasia of the subperitoneal mesenchyme [2]. About 100 documented cases were found in the English language literature; LPD patients are mainly females of reproductive age [3], and only rarely have cases affecting men been reported [4,5].
The condition is associated with high levels of exogenous and endogenous female gonadal steroids (e.g. pregnancy, prolonged exposure to oral contraceptives and/or combined hormonal replacement therapy, granulomatous cell tumours of the ovary) [4,6], indicating that oestrogens and progestins play an important role in the pathogenesis of LPD as they do in leiomyomata uteri.
Most LPD cases are clinically benign, and in some instances the lesions may partially or completely regress [5,7]. Alternatively, LPD may progress, recur or (rarely) undergo malignant transformation [8].
LPD is most common in women of reproductive age. More than half of all patients are pregnant or taking oral contraceptives at the time of diagnosis [14].
Quade et al. showed (in 1997) that LPD has molecular-genetic and cytogenetic features suggesting that individual tumourlets are monoclonal, with a pathogenesis similar to leiomyomata uteri. In LPD, the smooth muscle cells are influenced by oestrogens [7,15], and sex steroid receptors have been identified in nearly all cases [16]. LPD can be associated with other oestrogen-dependent diseases including endometriosis, ovarian clear cell carcinoma, endometrial carcinoma [17] and ovarian fibrothecoma [2]. Recently, two cases of development of LPD and ovarian Brenner tumour during tamoxifen [cancer drug] therapy have been reported [18-22].
Although LPD is most common in premenopausal women, cases have been reported in postmenopausal women using [23] or not using [13,24,25] hormone replacement therapy (HRT). The identification of luteinizing hormone (LH) receptors in LPD nodules from a postmenopausal woman suggests that the typical postmenopausal increase in LH levels might affect the pathogenesis of this condition [22].
Recently, familial occurrence of LPD has been described, showing an autosomal dominant model with varying degrees of penetrance [26].
Most patients with LPD present without specific symptoms and many documented cases of LPD have been discovered incidentally during surgery (caesarean section, laparotomy or laparoscopy). Sometimes patients may present with mostly non-specific symptoms, such as irregular, heavy uterine bleeding and pain or a mass in the lower abdomen [27], discomfort, urinary frequency (due to the effect of the mass on the bladder), gastrointestinal bleeding and peritonitis (following erosion of LPD implants in the bowel wall) [7,13,18,28]. Sometimes patients experience symptoms directly related to LPD: urosepsis secondary to obstruction of the ureters, and an acute abdomen due to ovarian torsion [29].
Sonographic and CT findings reported in the literature include non-specific, solid, and complex soft tissue masses that are often large and mimic a leiomyomatous uterus. In some cases, the masses grow in a fashion similar to that of normal uterine parenchyma, whereas others demonstrate heterogeneous enhancement. Diagnosis may be confused with peritoneal carcinomatosis if the masses are present diffusely throughout the abdomen and pelvis. Peritoneal carcinomatosis, however, is often associated with tumour cake, ascites and liver metastases, which have not been reported with LPD [29].
Magnetic Resonance (MR) findings include masses similar in signal intensity to skeletal muscle or uterine parenchyma, and when sarcomatous transformation occurs these are not significantly different from the features of benign implants. If the masses are located in the pelvis adjacent to the iliac vessels, they may be confused with lymphadenopathy [5,14,30-33]. Moreover, some multiple, pedunculated leiomyomas arising from the uterus may mimic LPD implants. Final diagnosis relies on histological examination [34] and immunohistochemical evaluation.
Sometimes, LPD may recur in patients taking HRT [13,24,25] even after hysterectomy and bilateral salpingo-oophorectomy [23], or in patients who have undergone in vitro fertilization [35]. Matthews and Speers reported a patient who died after a fourth recurrence of LPD and distant metastases 10 years after hysterectomy. Each recurrence seems to be more likely to produce morphological evidence of sarcoma [23].
Malignant transformation of LPD is uncommon and only ten cases have been documented in the English literature [8,29]. Of these, only three occurred in postmenopausal women (so seven cases of malignant transformation in premenopausal women)[29,36]. The interval between initial detection of LPD and the development of sarcoma varies from synchronous diagnosis to 8 years.
In most reports of malignant LPD, no history of oestrogen exposure was found. Bekkers hypothesized that LPD without exogenous or increased endogenous oestrogen exposure, and without expression of ER/PR by tumour cells, may represent a different entity carrying a higher risk of malignant transformation [3].
On the basis of these observations, we can affirm that no established guidelines exist regarding the management of LPD. However, therapy needs to be individualised according to the patient's age, hormonal and reproductive status and symptomatology. Different drugs (gonadotropin realising hormone agonist (GnRH agonist), megestrol acetate, danazol) have been considered in some cases but with poor results. If intestinal and bladder mass effect symptoms are prominent, a surgical approach is indicated [37]."
BMC Cancer. 2006; 6: 127.
Published online 2006 May 10. doi: 10.1186/1471-2407-6-127.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1481579
Telling LPD Articles
LPD Articles and Case Studies
- (2008) Anastrozole for LPD in a postmenopausal woman
- LPD induced by GnRH Agonist
- Progesterone receptor activity in leiomyomatosis peritonealis disseminata.
- Malignant Degeneration in Leiomyomatosis Peritonealis Disseminata
- Disseminated Peritoneal Leiomyomatosis Presenting as Severe Hypochromic Microcytic Anemia (2004)
- Posthysterectomy pelvic adenomyotic masses observed in 8 cases out of a series of 1405 laparoscopic subtotal hysterectomies.(2007)
- Removal of pelvic leiomyomata and endometriosis five years after supracervical hysterectomy.(2006)
- Recurrent leiomyomatosis peritonealis disseminata after hysterectomy and bilateral salpingo-oophorectomy during combined hormone replacement therapy.
- Leiomyomatosis peritonealis disseminata with malignant change in a post-menopausal woman.
- A Case of Leimyomatosis Peritonealis Disseminata Combined with Advanced Gastric Cancer [in a man]
- 2007, Aug. Computed tomography of pancreatic implantation with malignant transformation of leiomyomatosis peritonealis disseminata in a man.
- 2006, BMC Cancer,LPD Case Study (English)
- Peritoneal Cancer (including LPD)
- (2008) Anastrozole for LPD in a postmenopausal woman
Related Articles
- Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression, Aug. 2007
- estrogen receptor modulators and aromatase inhibitors against Benign Metastasizing Leiomyomas, The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 7 3183-3188
- Leiomyomatosis peritonealis disseminata occurring in a postmenopausal woman (1995,1996).
- Restoration of human chorionic gonadotropin response in human myometrial smooth muscle cells by treatment with follicle-stimulating hormone (FSH): evidence for the presence of FSH receptors in human myometrium. European Journal of Endocrinology, Vol 134, Issue 2, 225-231,
- Leiomyomatosis-Like Lymphangioleiomyomatosis of the Colon in a Female with Tuberous Sclerosis
- Dermatofibroma is a clonal proliferative disease
- Epstein-Barr Virus-associated Leiomyomatosis and Posttransplant Lymphoproliferative Disorder in a Child (2003)
- GnRH Agonist Explained, (blog with comments)
- Hormones Explained: LH, FSH, Estrogen etc.
- Leiomyomatosis-Like Lymphangioleiomyomatosis of the Colon in a Female with Tuberous Sclerosis
- CT Scans (LPD vs. other Neoplasms)
- Colon Leiomyomatosis [in a male]
- Smooth muscle tumors associated with X-linked Alport syndrome: carrier detection in females.
- clues to the pathogenesis of fibroids
- Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43.
- Treatments for Uterine Fibroids [also LPD?]
- 2007, Jun. Extra-uterine pelvic leiomyoma: diagnosis and practical management
- 2002, Prolonged GnRH Agonist and Add-Back Therapy
- Hormone-Dependent Tumor
Alternative and Complimentary Treatments. Hmmm...
- Calcium D Glucarate (by American Cancer Society)
- Calcium D-Glucarate (Spanish)
- 2007, Aug. Lycopene and other carotenoids inhibit estrogenic activity of 17beta-estradiol and genistein in cancer cells.
- 2007, Aug. Lycopene activity against chemically induced DNA damage in Chinese hamster ovary cells.
- 2007, Jul. What the FDA says about Lycopene
- Somebody I Know Cured His Cancer
- Chinese Herbal Therapy for Uterine Fibroids [and LPD?]
- Juicing Against Cancer (but not benign tumors like fibroids) - what about LPD?
- Calcium D Glucarate (by American Cancer Society)
- Calcium D-Glucarate (Spanish)
- Calcium D Glucarate (by American Cancer Society)
- Calcium D-Glucarate (Spanish)
Spanish Articles
- 2007. Miércoles 1 Agosto 2007. Cirugia Espanola. Volumen 82 - Número 02 p. 125 - 127 (Spanish). No Link.
- 2005, Leiomiomatosis Peritoneal Diseminada (Spanish)
- 2004, LPD (Spanish)
- 2004, Leiomioma disecante cotiledoneo de utero. Presentación de un caso y revisión de la literatura. (Spanish) Not exactly about LPD but related.
- 2004, (Spanish) Leiomiosarcoma bien diferenciado de ovario. [Not LPD but related]
- 2001, Cirugia Espanola, LPD Case Study (Spanish)
- 1998, Leiomiomatosis peritoneal diseminada. Presentación de un caso y revisión de la literatura (Spanish)
- 1998, Leiomiomatosis peritoneal diseminada. Presentación de un caso y revisión de la literatura (Spanish)
- 1997, LEIOMIOMATOSIS PERITONEAL DISEMINADA (DISSEMINATED PERITONEAL LEIOMYOMATOSIS )