Massive Localized Lymphedema of the Vulva: Report of a Case and Review of the Literature Debra S. Heller, MD,1,2 Valerie A. Fitzhugh, MD,1 Bernadette Cracchiolo, MD, MPH,2 Theodore Barrett Jr., MD,2 and Rudy S. Suidan, MD2 Departments of 1Pathology and Laboratory Medicine and 2Obstetrics, Gynecology, and Women’s Health, Rutgers New Jersey Medical School, Newark, NJ
h Abstract Massive localized lymphedema (MLL) is a recently described entity associated with obesity, most often on the thighs. It rarely occurs on the vulva, and it may pose diagnostic difficulty for both clinician and pathologist in this setting. Case. An obese 55-year-old woman underwent excision of bilateral polypoid vulvar masses. Histology confirmed the diagnosis of MLL. Conclusions. Although MLL is not common on the vulva, with the increasing incidence of obesity in the population, more cases can be anticipated, and an awareness of this lesion is important. h Background.
Key Words: vulvar diseases, lymphedema, obesity
M
assive localized lymphedema (MLL) is a recently described entity associated with obesity. It presents as a poorly circumscribed mass, often pedunculated. The most common location is the medial thigh, and it can interfere with ambulation. The first impression may be a soft tissue sarcoma. Rarely it occurs on the vulva, with fewer than 20 reported cases [1]. The highest Correspondence to: Debra S. Heller, MD, Department of Pathology, UH/ E158, UMDNJ-New Jersey Medical School, 185 S Orange Ave, Newark, NJ 07103. E-mail: [email protected] The author has declared that there are no conflicts of interest.
Ó 2013, American Society for Colposcopy and Cervical Pathology Journal of Lower Genital Tract Disease, Volume 18, Number 2, 2014, E46YE49
clinical association in all locations is obesity. In the vulva, the differential also includes aggressive angiomyxoma, which is more infiltrative, and more likely to recur. We present a case and review the literature.
CASE An obese 55-year-old postmenopausal woman G5P5005 presented with several years’ history of bilateral labial swelling, associated with pain and itching. Swelling was worsened by prolonged standing and walking and improved with lying down or wearing tight underwear and clothing. She had not had sexual intercourse for 5 years. Medical history was significant for poorly controlled diabetes mellitus, hypertension, asthma, history of septic arthritis of the right knee, atopic dermatitis, seizure disorder, and bipolar disorder. Surgical history was significant for 3 cesarean deliveries. The patient had a body mass index of 33 kg/m2. On examination, the patient was noted to have bilateral polypoid labial masses (right = 9.0 7.0 cm, left = 6.0 5.0 cm) that were firm, with no tenderness or erythema. This was associated with a peau d’orange appearance of the mons pubis and left perirectal ulceration. There were no other abnormalities on pelvic examination. A magnetic resonance image of the pelvis showed bilateral anterior exophytic vulvar masses associated with infiltration of the mons pubis (see Figure 1),
Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
Massive Localized Lymphedema of the Vulva
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Figure 1. Axial T2 magnetic resonance image demonstrates 2 exophytic, solid masses (see arrows) arising from the left and right anterior vulva with heterogeneous high signal intensity. The images abut each other at the midline and infiltrate the mons pubis.
no inguinal or pelvic lymphadenopathy, and a normalsized leiomyomatous uterus. Appearance at the magnetic resonance image was felt to be benign. The patient underwent a bilateral excision of the masses and left perirectal ulceration for symptomatology and cosmesis. Because of the benign impression on the magnetic resonance image, biopsy was not performed before excision. Pathology Grossly, the lesions were polypoid in configuration and covered by wrinkled skin (see Figure 2). Histologically, the lesion was poorly circumscribed and was composed of fibrillar collagen with interspersed adipose tissue. At
Figure 2. The excised masses were polypoid and covered by markedly wrinkled skin.
the junction of the collagen and adipose was a capillary proliferation, with influx of perivascular lymphocytes (see Figure 3). The lesion was positive for CD68, HHF35, CD34, and Factor XIIIA, and rare cells were stained for smooth muscle actin. The lesion was negative for S100, desmin, estrogen receptor, and progesterone receptor. A-Catenin was noncontributory. The combination of histologic and immunohistochemical findings resulted in a diagnosis of MLL.
DISCUSSION Massive localized lymphedema was first described in 1998 by Farshid and Weiss [2]. Massive localized lymphedema is a rare lesion in the vulva and uncommon
Figure 3. Histology showed an intertwining of adipose tissue and fibrillar collagen bundles, with prominent vessels at the interface. The vessels show a perivascular chronic inflammatory infiltrate.
Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
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in soft tissue. It is associated with obesity but has also been seen in association with immobilization, as well as after surgery or blunt trauma [3]. Not only is this lesion a challenge for providers who treat women but also for the pathologists who see these specimens as well. In 1 series, it was noted that many of the cases had been sent out in consultation and that the originating pathologist had frequently not received useful clinical information such as body habitus [4]. Most series report a female predominance [2, 4], and it usually is seen as a large pedunculated mass arising from the medial thigh [4], although a variety of other foci have been described, including abdominal pannus [5], penis, and scrotum [6, 7]. Our patient, in addition to the excised symptomatic vulvar lesions, seems to have continuity of the condition with the mons pubis. Massive localized lymphedema in the mons has also been reported [8]. Massive localized lymphedema is often a large polypoid lesion, poorly circumscribed, with overlying skin changes of ‘‘peau d’orange,’’ with dermal lymphangectasia and fibrosis, squamous cell hyperplasia (lichen simplex chronicus), and ulceration, as was seen in our case. Histologically, it is poorly circumscribed. There is a widening of fibroconnective tissue septa, proliferation of capillaries at the adipose/fibrous septal interface, and lymphocytic infiltration of the vascular tissue. The connective tissue septa can show lymphedema and contain rare multinucleated cells, scattered mildly atypical fibroblasts, and fibrillary collagen [2]. The adipose tissue lacks mitotic figures or lipoblasts, distinguishing it from liposarcoma [9]. In a literature review of vulvar lesions, Fadare et al. [2] found 17 cases and added 2 more. Age range was from 19 to 59 years, with a mean of 38.5 years. The lesions appeared as polyps, papillomatous plaques, massive pedunculated masses, or diffuse enlargement and had been present from 3 months to 36 years. Mean size was 6.1 cm. Excision of the lesions usually resulted in a cure; however, there were 3 cases of persistent disease. Local recurrence of MLL may occur in 14% to 50% of cases [10]. Rarely, subsequent development of a malignant lesion, angiosarcoma, has been described in MLL occurring in soft tissue [11]; hence, these patients need long-term follow-up. It has long been known that angiosarcoma can arise in the setting of longstanding lymphedema after breast cancer surgery (Stewart-Treves syndrome) [11]. The mechanism of MLL is thought to be lymphatic obstruction or alterations in hydrostatic/oncotic pressure [1]. Another possible contributing mechanism is
ischemia [12]. Of interest is an association in some reported cases with hypothyroidism [12], and perhaps the mechanism is similar to the development of myxedema. Differential diagnosis of vulvar MLL includes vulvar specific lesions, such as fibroepithelial polyps, angiomyfibroblastoma, cellular angiofibroma, and superficial myofibroblastoma, as well as aggressive angiomyxoma, which has a much higher recurrence potential [1, 13]. A variety of soft tissue neoplasms may also be of concern, such as liposarcoma [14], as well as vascular lesions and fibromatosis [4]. Liposarcoma is the most common histopathologic differential lesion. Liposarcoma is distinguished by the presence of atypical lipoblasts. If needed, a murine double minute 2 stain can be performed and will be positive in liposarcoma and negative in MLL. Imaging studies may help in the distinction because aggressive angiomyxoma is more likely to be deep-seated, whereas MLL is superficial, remaining above the fascia and sparing muscle [1, 12]. The soft tissue on imaging appears reticular [7]. Alcian blue staining will stain the myxoid stroma of aggressive angiomyxoma but not the lymphedematous stroma of MLL [1]. Massive localized lymphedema is more likely to show inflammatory cells around vessels and multinucleated cells, as well as alterations in overlying skin such as fibrosis, lymphangectasia, and squamous cell hyperplasia [1]. With the increasing incidence of obesity in the population, it is likely that more cases of vulvar MLL will present to clinicians. An awareness of this entity is important because the sarcomatous lesions in the differential carry much greater consequences. Clinicians should consider this as a possibility, particularly in obese patients. The lesion should also be familiar to pathologists who encounter gynecologic specimens. Of note, a superficial biopsy may make histopathologic diagnosis of this entity difficult, and adequate subcutaneous tissue is needed. Acknowledgment The authors thank Dr Robert Kurman for reviewing this case.
REFERENCES 1. Fadare O, Brannan SM, Arin-Silasi D, Parkash V. Localized lymphedema of the vulva: a clinicopathologic study of 2 cases and a review of the literature. Int J Gynecol Pathol 2011;30:306Y13. 2. Farshid G, Weiss SW. Massive localized lymphedema in the morbidly obese: a histologically distinct reactive lesion simulating liposarcoma. Am J Surg Pathol 1998;22:1277Y83. 3. Tenhagen M, Lodewijk L, Cense HA, Busch ORC. Clinical appearance and management of massive localized
Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
Massive Localized Lymphedema of the Vulva
lymphedema in morbidly obese patients: report of 2 cases. Updates Surg October 16, 2012 [E-pub ahead of print]. 4. Manduch M, Oliveira AM, Nascimento AG, Folpe AL. Massive localized lymphoedema: a clinicopathologic study of 22 cases and review of the literature. J Clin Pathol 2009;62: 808Y11. 5. Asch S, James WD, Castelo-Soccio L. Massive localized lymphedema: an emerging dermatologic complication of obesity. J Am Acad Dermatol 2008;59(suppl 5):S109Y10. 6. Lee S, Han JS, Ross HM, Epstein JI. Massive localized lymphedema of the male external genitalia: a clinicopathologic study of 6 cases. Hum Pathol 2013;44:277Y81. 7. Champaneria MC, Workman A, Kao H, Ray AO, Hill M. Reconstruction of massive localized lymphedema of the scrotum with a novel fasciocutaneous flap: a rare case presentation and a review of the literature. J Plast Rec Aes Surg 2013;66:281Y6. 8. Brewer MB, Singh DP. Massive localized lymphedema: review of an emerging problem and report of a complex case in the mons pubis. Ann Plast Surg. 2012;68:101Y4.
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9. Bogusz AM, Hussey SM, Kapur P, Peng Y, Gokaslan ST. Massive localized lymphedema with unusual presentations: report of 2 cases and review of the literature. Int J Surg Pathol 2011;19:212Y6. 10. Narayanarao T, Suvarchala A, Krishnababu G. Pseudosarcoma-massive localized lymphadema in morbidly obeseVa rare entity: case report. Int J Surg Case Reports 2012; 3:389Y91. 11. Shon W, Ida CM, Boland-Froemming JM, Rose PS, Folpe A. Cutaneous angiosarcoma arising in massive localized lymphedema of the morbidly obese: a report of five cases and review of the literature. J Cutan Pathol 2011;38:560Y4. 12. Wu D, Gibbs J, Corral D, Intengan M, Brooks JJ. Massive localized lymphedema: additional locations and association with hypothyroidism. Hum Pathol 2000;31:1162Y8. 13. Fitzhugh VA, Heller DS. Mesenchymal lesions of the vulva. J Low Genit Tract Dis 2011;15:134Y45. 14. Evans RJ, Scilley C. Massive localized lymphedema: a case series and literature review. Can J Plast Surg 2011;19: e30Y1.
Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
h Abstract Massive localized lymphedema (MLL) is a recently described entity associated with obesity, most often on the thighs. It rarely occurs on the vulva, and it may pose diagnostic difficulty for both clinician and pathologist in this setting. Case. An obese 55-year-old woman underwent excision of bilateral polypoid vulvar masses. Histology confirmed the diagnosis of MLL. Conclusions. Although MLL is not common on the vulva, with the increasing incidence of obesity in the population, more cases can be anticipated, and an awareness of this lesion is important. h Background.
Key Words: vulvar diseases, lymphedema, obesity
M
assive localized lymphedema (MLL) is a recently described entity associated with obesity. It presents as a poorly circumscribed mass, often pedunculated. The most common location is the medial thigh, and it can interfere with ambulation. The first impression may be a soft tissue sarcoma. Rarely it occurs on the vulva, with fewer than 20 reported cases [1]. The highest Correspondence to: Debra S. Heller, MD, Department of Pathology, UH/ E158, UMDNJ-New Jersey Medical School, 185 S Orange Ave, Newark, NJ 07103. E-mail: [email protected] The author has declared that there are no conflicts of interest.
Ó 2013, American Society for Colposcopy and Cervical Pathology Journal of Lower Genital Tract Disease, Volume 18, Number 2, 2014, E46YE49
clinical association in all locations is obesity. In the vulva, the differential also includes aggressive angiomyxoma, which is more infiltrative, and more likely to recur. We present a case and review the literature.
CASE An obese 55-year-old postmenopausal woman G5P5005 presented with several years’ history of bilateral labial swelling, associated with pain and itching. Swelling was worsened by prolonged standing and walking and improved with lying down or wearing tight underwear and clothing. She had not had sexual intercourse for 5 years. Medical history was significant for poorly controlled diabetes mellitus, hypertension, asthma, history of septic arthritis of the right knee, atopic dermatitis, seizure disorder, and bipolar disorder. Surgical history was significant for 3 cesarean deliveries. The patient had a body mass index of 33 kg/m2. On examination, the patient was noted to have bilateral polypoid labial masses (right = 9.0 7.0 cm, left = 6.0 5.0 cm) that were firm, with no tenderness or erythema. This was associated with a peau d’orange appearance of the mons pubis and left perirectal ulceration. There were no other abnormalities on pelvic examination. A magnetic resonance image of the pelvis showed bilateral anterior exophytic vulvar masses associated with infiltration of the mons pubis (see Figure 1),
Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
Massive Localized Lymphedema of the Vulva
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Figure 1. Axial T2 magnetic resonance image demonstrates 2 exophytic, solid masses (see arrows) arising from the left and right anterior vulva with heterogeneous high signal intensity. The images abut each other at the midline and infiltrate the mons pubis.
no inguinal or pelvic lymphadenopathy, and a normalsized leiomyomatous uterus. Appearance at the magnetic resonance image was felt to be benign. The patient underwent a bilateral excision of the masses and left perirectal ulceration for symptomatology and cosmesis. Because of the benign impression on the magnetic resonance image, biopsy was not performed before excision. Pathology Grossly, the lesions were polypoid in configuration and covered by wrinkled skin (see Figure 2). Histologically, the lesion was poorly circumscribed and was composed of fibrillar collagen with interspersed adipose tissue. At
Figure 2. The excised masses were polypoid and covered by markedly wrinkled skin.
the junction of the collagen and adipose was a capillary proliferation, with influx of perivascular lymphocytes (see Figure 3). The lesion was positive for CD68, HHF35, CD34, and Factor XIIIA, and rare cells were stained for smooth muscle actin. The lesion was negative for S100, desmin, estrogen receptor, and progesterone receptor. A-Catenin was noncontributory. The combination of histologic and immunohistochemical findings resulted in a diagnosis of MLL.
DISCUSSION Massive localized lymphedema was first described in 1998 by Farshid and Weiss [2]. Massive localized lymphedema is a rare lesion in the vulva and uncommon
Figure 3. Histology showed an intertwining of adipose tissue and fibrillar collagen bundles, with prominent vessels at the interface. The vessels show a perivascular chronic inflammatory infiltrate.
Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
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&
HELLER ET AL.
in soft tissue. It is associated with obesity but has also been seen in association with immobilization, as well as after surgery or blunt trauma [3]. Not only is this lesion a challenge for providers who treat women but also for the pathologists who see these specimens as well. In 1 series, it was noted that many of the cases had been sent out in consultation and that the originating pathologist had frequently not received useful clinical information such as body habitus [4]. Most series report a female predominance [2, 4], and it usually is seen as a large pedunculated mass arising from the medial thigh [4], although a variety of other foci have been described, including abdominal pannus [5], penis, and scrotum [6, 7]. Our patient, in addition to the excised symptomatic vulvar lesions, seems to have continuity of the condition with the mons pubis. Massive localized lymphedema in the mons has also been reported [8]. Massive localized lymphedema is often a large polypoid lesion, poorly circumscribed, with overlying skin changes of ‘‘peau d’orange,’’ with dermal lymphangectasia and fibrosis, squamous cell hyperplasia (lichen simplex chronicus), and ulceration, as was seen in our case. Histologically, it is poorly circumscribed. There is a widening of fibroconnective tissue septa, proliferation of capillaries at the adipose/fibrous septal interface, and lymphocytic infiltration of the vascular tissue. The connective tissue septa can show lymphedema and contain rare multinucleated cells, scattered mildly atypical fibroblasts, and fibrillary collagen [2]. The adipose tissue lacks mitotic figures or lipoblasts, distinguishing it from liposarcoma [9]. In a literature review of vulvar lesions, Fadare et al. [2] found 17 cases and added 2 more. Age range was from 19 to 59 years, with a mean of 38.5 years. The lesions appeared as polyps, papillomatous plaques, massive pedunculated masses, or diffuse enlargement and had been present from 3 months to 36 years. Mean size was 6.1 cm. Excision of the lesions usually resulted in a cure; however, there were 3 cases of persistent disease. Local recurrence of MLL may occur in 14% to 50% of cases [10]. Rarely, subsequent development of a malignant lesion, angiosarcoma, has been described in MLL occurring in soft tissue [11]; hence, these patients need long-term follow-up. It has long been known that angiosarcoma can arise in the setting of longstanding lymphedema after breast cancer surgery (Stewart-Treves syndrome) [11]. The mechanism of MLL is thought to be lymphatic obstruction or alterations in hydrostatic/oncotic pressure [1]. Another possible contributing mechanism is
ischemia [12]. Of interest is an association in some reported cases with hypothyroidism [12], and perhaps the mechanism is similar to the development of myxedema. Differential diagnosis of vulvar MLL includes vulvar specific lesions, such as fibroepithelial polyps, angiomyfibroblastoma, cellular angiofibroma, and superficial myofibroblastoma, as well as aggressive angiomyxoma, which has a much higher recurrence potential [1, 13]. A variety of soft tissue neoplasms may also be of concern, such as liposarcoma [14], as well as vascular lesions and fibromatosis [4]. Liposarcoma is the most common histopathologic differential lesion. Liposarcoma is distinguished by the presence of atypical lipoblasts. If needed, a murine double minute 2 stain can be performed and will be positive in liposarcoma and negative in MLL. Imaging studies may help in the distinction because aggressive angiomyxoma is more likely to be deep-seated, whereas MLL is superficial, remaining above the fascia and sparing muscle [1, 12]. The soft tissue on imaging appears reticular [7]. Alcian blue staining will stain the myxoid stroma of aggressive angiomyxoma but not the lymphedematous stroma of MLL [1]. Massive localized lymphedema is more likely to show inflammatory cells around vessels and multinucleated cells, as well as alterations in overlying skin such as fibrosis, lymphangectasia, and squamous cell hyperplasia [1]. With the increasing incidence of obesity in the population, it is likely that more cases of vulvar MLL will present to clinicians. An awareness of this entity is important because the sarcomatous lesions in the differential carry much greater consequences. Clinicians should consider this as a possibility, particularly in obese patients. The lesion should also be familiar to pathologists who encounter gynecologic specimens. Of note, a superficial biopsy may make histopathologic diagnosis of this entity difficult, and adequate subcutaneous tissue is needed. Acknowledgment The authors thank Dr Robert Kurman for reviewing this case.
REFERENCES 1. Fadare O, Brannan SM, Arin-Silasi D, Parkash V. Localized lymphedema of the vulva: a clinicopathologic study of 2 cases and a review of the literature. Int J Gynecol Pathol 2011;30:306Y13. 2. Farshid G, Weiss SW. Massive localized lymphedema in the morbidly obese: a histologically distinct reactive lesion simulating liposarcoma. Am J Surg Pathol 1998;22:1277Y83. 3. Tenhagen M, Lodewijk L, Cense HA, Busch ORC. Clinical appearance and management of massive localized
Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
Massive Localized Lymphedema of the Vulva
lymphedema in morbidly obese patients: report of 2 cases. Updates Surg October 16, 2012 [E-pub ahead of print]. 4. Manduch M, Oliveira AM, Nascimento AG, Folpe AL. Massive localized lymphoedema: a clinicopathologic study of 22 cases and review of the literature. J Clin Pathol 2009;62: 808Y11. 5. Asch S, James WD, Castelo-Soccio L. Massive localized lymphedema: an emerging dermatologic complication of obesity. J Am Acad Dermatol 2008;59(suppl 5):S109Y10. 6. Lee S, Han JS, Ross HM, Epstein JI. Massive localized lymphedema of the male external genitalia: a clinicopathologic study of 6 cases. Hum Pathol 2013;44:277Y81. 7. Champaneria MC, Workman A, Kao H, Ray AO, Hill M. Reconstruction of massive localized lymphedema of the scrotum with a novel fasciocutaneous flap: a rare case presentation and a review of the literature. J Plast Rec Aes Surg 2013;66:281Y6. 8. Brewer MB, Singh DP. Massive localized lymphedema: review of an emerging problem and report of a complex case in the mons pubis. Ann Plast Surg. 2012;68:101Y4.
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9. Bogusz AM, Hussey SM, Kapur P, Peng Y, Gokaslan ST. Massive localized lymphedema with unusual presentations: report of 2 cases and review of the literature. Int J Surg Pathol 2011;19:212Y6. 10. Narayanarao T, Suvarchala A, Krishnababu G. Pseudosarcoma-massive localized lymphadema in morbidly obeseVa rare entity: case report. Int J Surg Case Reports 2012; 3:389Y91. 11. Shon W, Ida CM, Boland-Froemming JM, Rose PS, Folpe A. Cutaneous angiosarcoma arising in massive localized lymphedema of the morbidly obese: a report of five cases and review of the literature. J Cutan Pathol 2011;38:560Y4. 12. Wu D, Gibbs J, Corral D, Intengan M, Brooks JJ. Massive localized lymphedema: additional locations and association with hypothyroidism. Hum Pathol 2000;31:1162Y8. 13. Fitzhugh VA, Heller DS. Mesenchymal lesions of the vulva. J Low Genit Tract Dis 2011;15:134Y45. 14. Evans RJ, Scilley C. Massive localized lymphedema: a case series and literature review. Can J Plast Surg 2011;19: e30Y1.
Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
