This paper was presented at the 44th Annual Meeting of the American Society of Dermatopathology, 21 October 2007 Baltimore, MD, USA.
Localized lymphedema (elephantiasis): a case series and review of the literature
Article first published online: 28 JUN 2008
© 2008 John Wiley & Sons A/S
Journal of Cutaneous Pathology
Volume 36, Issue 1, pages 1–20, January 2009
How to Cite
Lu, S., Tran, T. A., Jones, D. M., Meyer, D. R., Ross, J. S., Fisher, H. A. and Carlson, J. A. (2009), Localized lymphedema (elephantiasis): a case series and review of the literature. Journal of Cutaneous Pathology, 36: 1–20. doi: 10.1111/j.1600-0560.2008.00990.x
- Issue published online: 31 DEC 2008
- Article first published online: 28 JUN 2008
- Accepted for publication January 2, 2008
Background: Lymphedema typically affects a whole limb. Rarely, lymphedema can present as a circumscribed plaque or an isolated skin tumor.
Objective: To describe the clinical and pathologic characteristics and etiologic factors of localized lymphedema.
Methods: Case–control study of skin biopsy and excision specimens histologically diagnosed with lymphedema and presenting as a localized skin tumor identified during a 4-year period.
Results: We identified 24 cases of localized lymphedema presenting as solitary large polyps (11), solid or papillomatous plaques (7), pendulous swellings (4), or tumors mimicking sarcoma (2). Patients were 18 females and 6 males with a mean age of 41 years (range 16–74). Anogenital involvement was most frequent (75%) – mostly vulva (58%), followed by eyelid (13%), thigh (8%) and breast (4%). Causative factors included injury due to trauma, surgery or childbirth (54%), chronic inflammatory disease (rosacea, Crohn’s disease) (8%), and bacterial cellulitis (12%). Eighty-five percent of these patients were either overweight (50%) or obese (35%). Compared with a series of 80 patients with diffuse lymphedema, localized lymphedema patients were significantly younger (41 vs. 62 years old, p = 0.0001), had no history of cancer treatment (0% vs. 18%, p = 0.03), and had an injury to the affected site (54% vs. 6%, p = 0.0001). Histologically, all cases exhibited dermal edema, fibroplasia, dilated lymphatic vessels, uniformly distributed stromal cells and varying degrees of papillated epidermal hyperplasia, inflammatory infiltrates and hyperkeratosis. Tumor size significantly and positively correlated with history of cellulitis, obesity, dense inflammatory infiltrates containing abundant plasma cells, and lymphoid follicles (p < 0.05). A history of cellulitis, morbid obesity, lymphoid follicles and follicular cysts predicted recurrent or progressive swelling despite excision (p < 0.05).
Conclusions: Localized lymphedema should be considered in the etiology of skin tumors when assessing a polyp, plaque, swelling or mass showing dermal edema, fibrosis and dilated lymphatics on biopsy. A combination of lymph stasis promoting factors (trauma, obesity, infection and/or inflammatory disorders) produces localized elephantiasis.
The skin lymphatic system forms a vascular network that drains interstitial fluid from dermis and subcutis and returns it to the blood.1,2 Lymphatic vessels are also an important pathway for immune cell trafficking and antigen delivery.3 Impairment of lymphatic drainage due to (congenital) abnormal vessel development, damaged lymphatic vessels from infection, trauma, surgery or radiation, persistent inflammation or obstruction due metastases or parasite infestation causes stagnation of proteins and associated water in the interstitium, which leads to lymphedema.4–6 The protein-rich interstitial fluid of lymphedema leads to inflammation and an accumulation of fibroblasts, adipocytes and keratinocytes that transform the initially soft swollen tissue into a hard fibrotic tissue with stiff, thickened skin.2,3 Whole-limb (diffuse) lymphedema is typically a progressive and lifelong condition for which no curative treatment exists. Complications of lymphedema include impaired limb function, recurrent bouts of cellulitis – which aggravate the lymphedema and accelerate skin changes, and rarely malignancies such as lymphangiosarcoma (Stewart-Treves syndrome), squamous cell carcinoma, lymphoma, melanoma and Kaposi’s sarcoma.4–6
Probably because of limited collateral drainage, cutaneous lymphedema most commonly affects the extremities, but on careful examination, the lymphedema is more extensive with involvement of the associated quadrant of the trunk.4 In its earliest stages, lymphedema is soft and pitting; however, with persistence, lymphedema has a brawny, non-pitting appearance likened to peau d’orange because of accentuation of skin folds and follicular ostia. Most of the swelling occurs in the subcutaneous tissue, but the skin exhibits the most changes, which, when severe, is termed elephantiasis. Elephantiasis describes massive enlargement of a limb or the external genitalia because of chronic lymphedema, and it is characterized by brawny skin that resists wrinkling and is thickened with redundant skin folds, hyperkeratosis, verrucous papules and nodules, and florid papillomatosis.4–6 Histopathologically, lymphedema is a fibroinflammatory process.7,8 Typically, elephantiasis diffusely involves the body part affected by lymphedema (legs more than arms and genitalia episodically);8 exceptionally, lymphedema involves circumscribed region of skin producing a solitary, large polyp,9–29 indurated (solid) plaque,30–68 papillomatous plaque,69–80 pendulous swelling81–90 or large, sarcoma-like mass.91–115 Herein, we report the clinicopathologic findings of a consecutive series of 24 cases of localized lymphedema (elephantiasis) and review the literature on this phenomenon.
Material and methods
A retrospective case–control study of localized polypoid, pendulous or tumefactive lymphedema (elephantiasis) was performed. Potential cases were first identified by a natural language computer search for the diagnostic description of ‘lymphedema’ over a 4-year period (2003–2006) on pathology reports from skin or anogenital specimens from the Department of Pathology, Division of Dermatopathology at Albany Medical College (Table 1). From this pool of cases, a second selection was made based on the clinical data submitted with the pathology report. Specifically, the cases selected for study were those cases that had a clinical description of a localized tumor depicted as a ‘mass’, ‘swelling’, ‘tumor’, ‘plaque’, ‘lesion’, ‘tag’, ‘wart’, ‘hemorrhoid’, ‘condyloma’, or ‘polyp’ (Table 2). From this cohort of localized, tumorous lymphedema or elephantiasis, all demographic and clinical information were retrieved from the pathology records, hospital records and the submitting physician’s clinical notes. All histologic material was retrieved for light microscopy review. Cases were excluded from the study if they did not show the minimal histologic criteria for lymphedema, consisting of dermal edema, fibroplasia (increase in fine, widely spaced, dermal collagen bundles), dilated lymphatic vessels and uniformly distributed spindle and dendritic cells (Fig. 1). In addition, if the patients had a history of previous biopsy or excision from the affected site, the original biopsy material was retrieved and histologically reviewed.
|Number (%)||Age*||Female:male ratio||Localized lymphedema, n (%)†||Cancer (%)‡||Injury (%)‡||Chronic inflammation (%)‡||Infection (%)‡||Unknown cause (%)§|
|All cases||104||57 ± 19 (1.5–95)||77:27 (3:1)||24 (23)||13||14||27||14||38|
|Diffuse lymphedema||80||62 ± 17 (1.5–95)||59:21 (3:1)||18||6||29||15||38|
|Localized lymphedema†||24||41 ± 14 (16–74)||18:6 (3:1)||0||54||8||12||29|
|Anogenital (vulva¶)||28 (26)||44 ± 18 (1.5–85)||24:4 (6:1)||18 (75)||4||33||18||15||29|
|Extremities (leg¶)||17 (16)||64 ± 15 (34–88)||12:5 (5:2)||2 (12)||12||6||35||18||29|
|Head and neck (eyelid¶)||38 (37)||66 ± 12 (43–93)||22:16 (5:4)||3 (8)||8||10||28||8||54|
|Trunk (breast¶)||21 (20)||51 ± 21 (14–98)||20:1||1 (5)||40||5||25||20||25|
|Case||Age||Sex||Site||Morphology (size, cm)*||Duration||Clinical diagnosis||Associated (etiologic) factors||Additional histologic findings†||Body mass index‡||Recurrence (time)|
|1||39||M||Perianal||Polyp (1.5)||1 year||Perianal skin tag||Trauma||Perifolliculitis, LSC, scar,||29||UK|
|2||41||M||Perianal||Polyp (2.5)||> 2 years||Hemorrhoid||UK||LSC, scar||22||UK|
|3||33||F||Perianal||Polyp (1)||1 year||Skin tag||fourth degree perineal laceration during NSVD||LSC||25||None (2 years)|
|4||53||F||Perianal||Verrucous plaque (2.7)||1 year||Abscess||Crohn’s disease with fistula-in-ano and seton stitches||LSC, scar, syringofibroadenoma, papillomatosis||29||None (5 months)|
|5||61||M||Penis, meatus||Pedunculated, cauliflower-like mass (4.5)||3 months||Giant condyloma||Lysis of urethral stricture||Lymphoid follicles. LSC, papillomatosis, scar||70||None (12 months)|
|6||25||F||Vulva-vagina||Papillomatosis plaque (3)||3 months||Polyposis, dyspareunia||NSVD, episotomy site||Papillomatosis, scar||27||Recurrence (6 months)|
|7||46||F||Vulva||Papillomatous plaque (14)||36 years||Condyloma, cellulitis||Multiple vulvar surgeries, DM, HTN, RI, cellulitis, mother has lymphedema||Cysts, perifolliculitis, granulomas, LSC, papillomatosis, scar||40||Persistent disease (7 months)|
|8||50||F||Vulva||Polyps x2 (1.2)||2 years||Papillomas||NR||LSC, scar||26||None (36 months)|
|9||53||F||Vulva||Polyp (1)||UK||Skin tag||None||LSC, papillomatosis, scar||NR||NR|
|10||37||F||Vulva||Pendulous tissue (3)||Years||Redundant labia, dyspareunia||HPV anogenital region, excision and ablative therapy||LSC, papillomatosis||26||None (24 months)|
|11||26||F||Vulva||Polyp (2)||6 months||Skin tag||Occurred after NSVD||Lichen sclerosus, scar||25||None (17 months)|
|12||27||F||Vulva||Polyp (2)||3 months||Condyloma||Pregnancy related, excised after NSVD||Fibrosing neutrophilic vasculitis, LSC, papillomatosis||28||UK|
|13||28||F||Vulva||Polyp (1.5)||UK||Skin tag||NR||LSC, papillomatosis||NR||NR|
|14||59||F||Vulva||Polyp (0.6)||UK||Lesion||UK||Cysts, perifolliculitis, granulomas, LSC, scar||30||None (12 months)|
|15||39||F||Vulva||Papillomatous Plaque (1)||2 years||Lesion||Vaginal prolapse and rectocele||Papillomatosis||36||None (24 months)|
|16||38||F||Hymen||Polyp (1)||1 year||Skin tag||Pregnancy, 2° perineal tear||None||24||None (8 months)|
|17||40||F||Vulva||Plaque (1.5)||2 years||Mass||Pregnancy NSVD 2 years ago, vulvar cryosurgery (age 19)||Candidiasis, papillomatosis, scar||24||None (6 months)|
|18||19||F||Vulva||Pendulous tissue (5)||>2 years||Redundant labia||NR||LSC, peri-sebaceous adenitis||NR||NR|
|19||34||M||Thigh||Papillomatosis plaque (20)||>3 years||Papillomatosis plaque||Quadriplegic, ulcers, skin graft at site, cellulites||Cysts, folliculitis, granulomas, LSC, papillomatosis, scar||40||Persistence|
|20||49||F||Thigh, abdomen||Mass, 9.5 kg (30)||2–3 years||Cellulitis, necrotic tumor||Cellulitis, DM, hypothyroidism, HTN||LSC, lymphoid follicles, scar||60||Persistent edema at site (8 months)|
|21||43||F||Conjunctiva||Plaque (1.5)||2 years||Lesion||Retinal detachment, scleral buckle removed 7 years ago, scar||Eosinophils, lymphoid hyperplasia, scar||25||None (23 months)|
|22||59||M||Eyelid||Pendulous swelling (2.5)||1 year||Infiltrative process, rule out cancer||Rosacea, DM, congestive heart failure, lower leg edema||Perifolliculitis, folliculitis, demodex||60||Progression (73 months)|
|23||74||M||Eyelid||Pendulous swelling (5)||NR||Dermatochalasis||UK||Perifolliculitis||25||None (42 months)|
|24||16||F||Breast||Mass (3)||NR||Hemangioma||NR||Perifolliculitis, scar||NR||NR|
In addition to light microscopic review of hematoxylin and eosin (H&E) stained tissue sections, evaluation of elastic tissue content was assessed by Verhoeff-Van Gieson (VVG) staining. Utilizing the Ventana ES automated DAB immunohistochemical system (Ventana Medical System, Tucson, AZ, USA), the expression of the following proteins was evaluated: actin (prediluted; Ventana Medical Systems), CD31 (1 : 20; Dako, Carpinteria, CA, USA), CD34 (prediluted; Ventana Medical Systems), CD68 (1 : 100; Dako), D2-40 (1 : 200; Dako), desmin (prediluted; Ventana Medical Systems), Factor XIIIa (1 : 1000; CalBiochem, San Diego, CA, USA), S-100 protein (prediluted; Ventana Medical Systems), smooth muscle actin (1 : 100; Vector Laboratories, Burlingame, CA, USA), and vimentin (1 : 400; Dako).
Statistical analysis was carried out with the STATA (College Station, TX) statistical package. Differences between groups were tested by the chi-square test for dichotomous variables and by the Student’s t-test for continuous variables. Correlations between study variables were examined by linear regression and pairwise covariance methods. Prediction of outcome (recurrent tumor growth and/or progression to involve surrounding area) was assessed using logistic regression methods. The criterion for significance was p ≤ 0.05.
A total of 104 cases were identified from 64,500 dermatopathology reports (0.002%) with the histologic diagnosis of lymphedema. Lymphedema was not clinically suspected or listed as a co-morbid condition in any patient. Table 1 summarizes the demographic data, site of lymphedema and probable etiologic factor for lymphedema in this cohort. Of these patients with lymphedema, 24 (23%) had localized lymphedema. Compared with patients with diffuse lymphedema, localized lymphedematous patients were significantly younger (41 vs. 62 years old, p = 0.0001), did not have any form of cancer treatment (0% vs. 18%, p = 0.03), were significantly more likely to have history of trauma to the site (54% vs. 6% p = 0.0001), and less likely to have a coexisting, chronic inflammatory process (8% vs. 29%, p = 0.03). The anogenital region was significantly more frequently affected by localized lymphedema compared with cases of diffuse lymphedema [18/24 (75%) vs. 10/80 (12%), respectively] than the extremities (8% vs. 20%), the head and neck (12% vs. 41%), and the trunk (8% vs. 24%; p = 0.0001). No etiology or associated disease was found in about one-third of all cases; in the case of eyelid lymphedema, these patients had surgery for ptosis because of dermatochalasis or blepharochalasis from an unknown inflammatory cause. Overall, women were more frequently affected by lymphedema, particularly in the anogenital region and trunk, than men with a mean ratio of 3 : 1; trunk (breast) involvement had the highest female to male ratio of 20 : 1.
Table 2 lists the clinical and pathologic findings of patients identified with localized lymphedema. This series of patients consisted of 18 females and 6 males (ratio 3 : 1) with mean and median age of 41 and 40 years (range 16–74). The tumors were long standing; the duration of these lymphedematous tumors ranged from 4 months to 36 years, with a mean and median duration of 3.3 and 2 years, respectively. The most common clinical presentation was an isolated, polypoid tumor found in 46%, followed by a solid or papillomatosis plaque in 29%, a pendulous swelling in 17% and a large mass in 8%. The anogenital region was most frequently affected (75%) and polypoid tumors were found only in this region, found in 11/18 (61%). The eyelid and conjunctiva were involved in 12%, chest or abdomen in 4% and extremity (thigh) in 8%. Notably, the majority of patients, 85%, had a body mass index (BMI) greater than normal (> 18.5 and < 25) with a mean and median BMI of 34 and 28, respectively, with a range of 22–70. Half of these patients were classified as overweight (BMI ≥ 25 and < 30) and 35% as obese (10%) or morbidly obese (25%) (BMI ≥ 30 and < 40, and BMI ≥ 40, respectively). A history of trauma to the region occurred in 54% of patients, most frequently because of a recent spontaneous vaginal delivery (25%) associated with vulvovaginal and/or perineal tear or an episotomy. Episodes of cellulitis occurred in three patients (13%). Two patients (8%) had coexisting chronic inflammatory diseases, rosacea and Crohn’s disease, affecting the involved site. In 7/24 (39%) cases, no known causative factor or associated medical condition could be identified to explain the presence of tumorous, localized lymphedema. After mean and median follow-up time of 20 and 14 months, respectively (range 5–73 months), tumor persistence or progression occurred in 28% after excision or tumor debulking. Patients who had tumors greater than 3 cm in size, or who were obese (BMI ≥ 30) were significantly more probable to have tumor persistence or recurrence than those who had small tumors or had BMI < 30 (both 57% vs. 10%.; p = 0.04, chi-square test). In addition, all three patients with history of cellulitis had large tumors (mean size 21 cm vs. 2 cm, p = 0.02, Student’s t-test, considering unequal variance). By logistic regression analysis, the history of cellulitis and obesity (BMI ≥ 30) significantly predicted for poor outcome (p ≤ 0.05) and a trend implicating a tumor size greater than 3 cm (p = 0.08).
The histologic features that varied among the cases were the density and distribution of the inflammatory infiltrates, the composition of the infiltrates and the presence or absence of superficial lymphangioma-like areas, dermal scarring (dense dermal fibrosis), papillomatosis, follicular (epidermoid) cysts, folliculitis and perifolliculitis, and lichen simplex chronicus (psoriasiform epidermal hyperplasia, hypergranulosis and hyperkeratosis). Table 3 summarizes the pathologic findings for all the cases. It is notable that six patients exhibited a scar out of eight patients who did not report trauma to the site or the history was unknown. If a scar is assumed to represent evidence of past trauma to the region, then skin injury occurred at the site of localized lymphedema in 79% of this cohort. Neutrophilic infiltrates were associated with acute suppurative folliculitis with the exception of case 12 with leukocytoclastic vasculitis. Case 12, vulvar lymphedematous fibroepithelial polyp, exhibited a large fibroinflammatory nodule attributed to chronic localized fibrosing leukocytoclastic vasculitis, which is one cause of cutaneous inflammatory pseudotumors.116 Other singular histologic observations included: case 11, vulvar lymphedematous fibroepithelial polyp with coexisting lichen sclerosus, which has been described in conventional fibroepithelial polyps117 and case 21, indurated conjunctival plaque that arose after scleral buckle removal, which had an eosinophil-rich inflammatory infiltrate implicating a hypersensitivity reaction, perhaps to retained scleral buckle material.
|All cases||Tumor size||p value||Body Mass Index||p value||Cellulitis History||p value|
|Summary (%)||≤ 3 cm (n = 18) (%)||> 3 cm (n = 6) (%)||< 25 (n = 3) (%)||≥ 25 and < 30 (n = 10) (%)||≥ 30 (n = 7) (%)||Absent (n = 21) (%)||Present (n = 3) (%)|
|Density of inflammation|
|Superficial and deep perivascular||42||39||50||33||60||46||38||67|
|Predominately plasma cells||33||20||67||0.06||0||30||71||0.07||24||100||0.03|
|Scar/dense dermal fibrosis||67||67||67||NS||67||60||86||NS||62||100||NS|
|Lichen simplex chronicus||79||72||100||NS||33||80||86||NS||76||100||NS|
Several histologic features significantly correlated with increasing tumor size: increasing density of the inflammatory infiltrate (r = 0.2, p = 0.03, linear regression), increasing plasma cell density (r = 0.4, p = 0.03, pairwise covariance analysis), and increasing frequency of lymphoid follicles (r = 0.6, p = 0.001, pairwise covariance analysis). Tumors greater than 3 cm were more likely to have a moderate or dense inflammatory infiltrate that was composed mostly of plasma cells and significantly more likely to have lymphoid follicles (p = 0.006, chi-square test) (Table 3). Tumors from patients with morbid obesity were significantly more probable to show dense inflammatory infiltrates associated with granulomas and/or lymphoid follicles, have superficial lymphangioma-like areas and show follicular cysts (p ≤ 0.04, chi-square test) (Table 3). Patients with a history of cellulitis were significantly more likely to have a dense inflammatory infiltrate consisting predominately of plasma cells that was associated with granulomas, lymphoid follicles and/or follicular cysts (p ≤0.03, chi-square test) (Table 3). With respect to outcome, the presence of lymphoid follicles or follicular (epidermoid) cysts significantly predicted for local recurrence or persistent swelling (20/16 odds ratio, respectively, p ≤0.04 logistic regression); no other histologic features predicted for adverse outcome. Several correlations were also identified amongst the histologic findings evaluated. The presence of superficial lymphangiomas was significantly related to increased plasma cell density (r = 0.4, p = 0.03, pairwise covariance analysis) (Fig. 2). Lastly, a positive relationship was identified for granulomas and follicular cysts (r = 0.8, p = 0.0001, pairwise covariance analysis).
Analysis of elastic tissue
Evaluation of elastic tissue content by VVG staining revealed fragmentation, clumping, and/or loss of mature elastic fibers throughout the reticular dermis and submucosa. In the papillary dermis and areas of superficial fibrous edema, fine, widely spaced and crisscrossing elastic fibers (oxytalan and elaunin) could be identified (so-called dissociation of elastic fibers118) (Fig. 3).
The stromal multinucleate and dendritic cells strongly and diffusely expressed vimentin. At most, one-half of all dendritic stromal cells expressed factor XIIIa. CD68 was expressed by a lesser number of stromal cells, mostly macrophages and multinucleated stromal cells (< 25%) (Fig. 3). No dermal stromal cells expressed CD34; however, a minority of spindle and dendritic cells of subcutaneous septae in the case of massive localized lymphedema (case 20) expressed CD34. Rare macrophages were labeled by S-100 protein, mostly within subepidermal lymphocytic infiltrates. S-100 protein also highlighted intraepidermal Langerhans’ cells, whose numbers did not appear to be either increased or decreased within the spinous layer. Desmin, smooth muscle actin and actin were not expressed by stromal cells, but were expressed by the media of the muscular vessels.
All endothelial cells of small and muscular vessels and lymphatics expressed CD31 and CD34. Dilated lymphatics also expressed CD31 and CD34, but with less intensity and often in a discontinuous pattern. D2-40 expression was limited to lymphatic endothelium, which represented at most 25% of all vessels. In some tumors, basal keratinocytes of both keratinizing and non-keratinizing squamous epithelium regionally expressed D2-40 in a membranous pattern (Fig. 4).
Following below are the clinicopathologic findings and course of vulvar lymphedematous fibroepithelial polyps and four unusual cases of patients who had severe, localized elephantiasis at various sites. From a clinical viewpoint, these latter four cases were diagnostically challenging as no one suspected lymphedema with progression to elephantiasis as the underlying cause for the tumors.
Illustrative case reports
Cases 8, 9, 11–14 and 16: vulvar lymphedematous fibroepithelial polyps
These seven women all presented with firm, asymptomatic vulvar polyps of 1-year duration (range 3 months to 2 years) clinically suspected to be conventional skin tags/fibroepithelial polyps or condyloma. In three cases, the polypoid tumor occurred within 1 year after normal spontaneous delivery; no known etiologic factor was reported for the other cases. Of the patients whose BMI was known, only one was morbidly obese. Histologically, the lymphedematous polyps had minimal superficial inflammatory infiltrates. Numerous multinucleated cells could be found throughout the edematous fibrotic stroma (Fig. 5). No recurrences or persistence was reported after excision with mean follow-up time of 18 months (range 8–36 months).
Case 5: large lymphedematous polyp of the penis
A 61-year-old white male was referred to Urological Surgery Department in Albany Medical Center for a 1-year history of a progressively enlarging, distal polypoid penile mass that arose 3 months after dilation of a bulbar urethral stricture. Clinically, the tumor was suspected to be giant condyloma, verrucous carcinoma, or squamous cell carcinoma (Fig. 6). He was morbidly obese (BMI = 70) and had hypercholesterolemia and varicose veins. On examination, the tumor was 4-cm pedunculated, cauliflower-like lesion attached by 1-cm stalk to the inferior lip of the urethral meatus near the coronal sulcus in the midline over the urethra. The shaft of penis, bilateral testes and epididymides were all normal. The mass was excised and urethroplasty performed. During the surgery, inspection of the base of the polyp revealed firm, fibrotic tissue. Histologic examination revealed fronds and digitations with lymphedematous core (edematous fibrosis with lymphangiectases), regions of superficial lymphangioma formation, and deep dermal scarring with plasma cell predominate inflammatory infiltrate and lymphoid follicle formation (Fig. 7). After 12-month follow up, he has not experienced a recurrence.
Case 7: papillomatous plaque of vulva associated with follicular cysts
A 46-year-old female, morbidly obese (BMI = 40) presented for medical care because of lower abdominal and vulvar cellulitis and a 14-cm papillomatous vulvar plaque, clinically suspected to be condyloma acuminatum. She had a long history of anogenital tumors. At the age of 10, she was diagnosed with rectal ‘warts’. At the age of 23, she developed ‘wart’-like lesions in the vaginal area, which were burning and painful. In the following years, these lesions increased in number and size, resulting in multiple vulvovaginal resections. Ten years before this surgery, a 10-pound, inflammatory mass was removed. Her medical history was significant for diabetes mellitus, hypertension and renal insufficiency. Her mother had elephantiasis of the lower extremities. The patient received antibiotics for cellulitis and the vulvar mass was surgically excised (Fig. 8). Histologically, in addition to the common characteristics of lymphedema, dense plasma-cell-rich infiltrates and lymphoid follicles were present often adjacent to ectatic vascular spaces. In addition, scattered granulomas could be found, often in the vicinity of small infundibular cysts (Fig. 8). These later features implicated the possibility of coexisting hidradenitis suppurativa, a reported cause of localized elephantiasis.50,70,77,101,102,115 After 7-month follow up, she still has vulvar and perineal swelling.
Case 19: papillomatous plaque of thigh after skin graft harvest
A 32-year-old white male was referred for treatment of persistent ‘verrucous’ plaques affecting the hips and upper thighs. He was quadriplegic because of traumatic spine injury 7 years ago. This moribund condition was complicated by morbid obesity (BMI = 40), anasarca and deep venous thromboses. With respect to his cutaneous findings, he first presented with foul smelling verrucous papules at these locations that drained clear yellow fluid. Culture of these sites revealed mixed bacterial infections. These initial lesions persisted and expanded after excision and massage therapy. Over the 2 years preceding this medical visit, he had had multiple excisions that progressively grew wider, some of which required skin grafts. Despite debulking and excision, his verrucous tumors progressed to involve skin graft and donor sites. One of the most notably histologic features common to all his biopsy and excision specimens were the presence of superficial and deep plasma-cell-rich infiltrates, lymphoid follicles, rare aggregates of foreign body type giant cells and small follicular cysts (Fig. 9). Antibiotics, excision and massage therapy have not resulted in diminishment of his verrucous plaques.
Case 22: pendulous swellings of the eyelid secondary to rosacea
A 59-year-old, morbidly obese (BMI > 60) white male first presented for medical care with a large left upper eyelid ‘mass’ that created a marked secondary ptosis and obstructed his vision (Fig. 10). This tumor was successfully treated with ‘debulking’ excision and pathologically interpreted as chronic lymphedema. No known cause was determined for its appearance such as ocular trauma, erysipelas, angioedema, thyroid disease or systemic lupus erythematosus. Over the next 5 years, he developed central facial erythema, mild rhinophyma and progressive swelling of both lower eyelids and his right upper eyelid (Fig. 10). The changes were similar in quality to those noted on his initial presentation for the left upper lid. Allergy testing performed by another physician was negative. He did not have a furrowed tongue or facial weakness. Additional biopsies of the right upper and lower lids revealed chronic lymphedema, lymphocytic perifolliculitis and rare foci of suppurative folliculitis (Fig. 11). Based on the clinical and pathologic findings, rosacea was diagnosed and treated with minocycline 100 mg b.i.d. After 1 month of minocycline therapy, no clinical improvement was noted. In all, he has experienced 61 months of persistent and progressive lymphedema.
Lymphedema is not a reportable disease, so epidemiologic data is scant. Worldwide, an estimated 140–250 million people suffer from lymphedema, mostly because of filariasis in developing nations.119 In Germany, the German Society of Phlebology (Bonner Venestudie, 2003 from119) estimated the prevalence of lymphedema to be 1.8% (2% women; 1.5% men). In Western countries, the populations primarily affected by lymphedema are patients treated for malignancy, particularly women with breast and gynecologic cancer.6,119–122 For breast cancer treatment, the frequency of arm lymphedema 9.5 years after treatment varies dependent on the type of surgery and use of adjuvant radiotherapy from 21% after lumpectomy without postoperative radiation therapy to 40% after modified radical mastectomy with postoperative radiation therapy.123 Lower extremity lymphedema is most prevalent for vulvar cancer patients at 36%.121 In contrast, for minor surgery without lymphadenectomy, the frequency of transient or permanent lymphedema is unknown. In addition to trauma and surgery, chronic inflammatory dermatoses can cause or exacerbate pre-existing lymphedema.119,124 For example, 24% of rosacea patients have lymphedema as assessed by clinical examination.125 In non-phymatous rosacea, alterations in lymphatic homeostasis may occur early as significantly increased expression of vascular endothelial growth factor (VEGF) and increased number of lymphatics has been observed compared with non-lesional skin.126 This case series culled from 4 years of skin biopsy and excision specimens from a community and tertiary dermatopathology service serving the Capital District of New York (population of 794,293 in the year 2000) has shown that chronic localized (tumorous) lymphedema is exceptionally rare. Compared with the more common presentations of diffuse, whole-limb lymphedema, local skin injury because of trauma or non-cancer-related surgery is the presumptive etiologic factor in over half of patients by history and in over three-quarters by history and histologic evidence of scarring. Chronic inflammatory disorders and infection (cellulitis) play a primary role in a minority of cases. Abnormally high BMI was a significant cofactor in the majority of cases. Similarly, review of the world’s literature reveals that localized lymphedema is a rare phenomenon, documented mostly as case reports and as a handful of small case series.
The world’s literature was searched for reports describing ‘localized lymphedema’, ‘localized elephantiasis’, ‘elephantoid lymphedema’, ‘lymphedematous’ tumors, lymphedema/elephantiasis affecting an isolated body part such as the ear, nose, eyelids, face or anogenital region (filarial scrotal elephantiasis cases were excluded), and lymphedema complicating chronic, localized inflammatory dermatoses. The details listed in Table 4 reveal a demographic profile, spectrum of clinical and pathologic findings, outcomes and etiologic factors comparable to those described for our case series. One of the most striking features of all these reports is the plethora of names used to classify these presentations, some of which recognize the lymphedematous nature of the tumors (e.g. massive localized lymphedema and lymphedematous fibroepithelial polyps), others that recognize the underlying disorder (e.g. rosaceous lymphedema and scar lymphedema), and some that simply label the disease based on the clinical presentation (e.g. stasis papillomatosis and solid persistent facial edema). The average age of patients affected was 45 years (mean of means) with means per body site ranging from 19 years for facial involvement to 63 years of age for nasal involvement. Interestingly, overall more cases of male involvement were found [131 vs. 105 (mean ratio 4 female to 5 males)], which could be attributed to reporting bias based on site of involvements. Anogenital reports of localized lymphedema were relatively equal between the sexes. However, facial, nose, ear and eyelid lymphedema was more common in males than females (because of more severe acne and more frequent phymatous rosacea in men127), and abdomen and lower extremity localized lymphedema was more commonly reported in females (because of higher prevalence of morbid obesity and sedentary habits128). Lymphedematous tumors ranged from polypoid tumors in the anogenital region, to solid plaques with or without papillomatosis affecting all sites, to large masses associated with obesity affecting the scrotum, proximal limbs or abdomen. The majority of patients did not have recurrence after excision or debulking surgery. While local injury (i.e. surgery, trauma or vaginal delivery) was reported factor in many cases, morbid obesity, underlying systemic disease like hypothyroidism and diabetes mellitus, chronic inflammatory disorders involving the folliculosebaceous unit like rosacea, acne vulgaris and hidradenitis suppurativa, and bacterial cellulitis were also commonly reported as the underlying etiologic factors. The pathologic findings of these varied cases lead to the recognition that chronic lymphedema with progression to elephantiasis was the underlying pathogenesis for the tumors.
|Site||Sex||Age||Morphology size||Duration||Associated (etiologic) factors||Other nosology||Treatment||Outcome||References|
|Abdomen (pannus)||7 F, 1 M||∼48 years (26–76)||Mass, nodules; up to 59 cm or 19 kg||Months–4 years||Cellulitis; congestive heart failure; hypothyroidism; Ischemia; morbid obesity||Elephantiasis nostras cutis; massive localized lymphedema; massive localized lipolymphedema pseudotumor; verrucous and elephantoid lymphedema||Panniculectomy, wide local excision||No recurrence, majority; recurrence, minority||91,92,94,96,98,100,105|
|Anus||18 F, 22 M||47 years (17–74)||Polyps, 0.9 cm, 0.5–4 cm||NR||Local irritation, injury or infection, pregnancy||Anal papillae, fibroepithelial polyp of the anus||Excision||No recurrence||13, 18–20|
|Arm||2 F, 1 M||38 years (2–58)||Plaque, mass, 28 and 40 cm||NR||Linear morphea, morbid obesity||Massive localized lymphedema||Excision||NR||54,93|
|Ear||13 F, 16 M||39 years (4–66)||Enlargement, polyps unilateral 44%||9.6 years (0.5–30)||Eczema, erysipelas, pediculosis capitis, psoriasis, rosacea, trauma (frost bite)||Otophyma, elephantiasis||Debulking, ILCS, rosacea therapy, testosterone||Improvement, all||57–65,67,79,80|
|Eyelids||4 F, 7 M||61 years (44–88)||Swelling, plaque, unilateral 54%||20 months (3 weeks to 6 years)||Erysipelas, rosacea, SCC with radical neck dissection and XRT||Blepharophyma, chronic eyelid lymphedema 2nd to acne rosacea, elephantoid edema of the eyelids, lymphedema of eyelids, Morbihan’s disease, periorbital edema, periorbital lymphedema, rosacea lymphedema||Debulking, blepharoplasty, oral anti-rosacea Rx||Recurrence/persistence 54%, improved 46%||52,81,83-88|
|Face||9 F, 28 M||19 years (17–25)||Plaque(s) of central face (forehead, eyelids, nasal saddle, nasolabial folds, and cheeks); ‘upstream’ scar swelling||1.6 years (9 days to 13 years)||Acne, lymphoma, orofacial granulomatosis (Melkersson-Rosenthal syndrome), rosacea, U-shaped (trapdoor) scars||Morbihan’s disease, rosacea lymphedema, scar lymphedema, solid persistent facial edema||Isotrentoin, lymph massage, surgery/scar revision||Improvement 54% with isotrentoin, scar revision – improvement 75%||30–44,46,47,49,51,53,55,56,82,89|
|Foot||2 F, 1 M||57 years (42–80)||Mass (unilateral 33%), 5 cm||NR||Alcoholic neuropathy and hepatopathy, hypothyroidism, ischemia, morbid obesity||Elephantiasis nostra cutis, localized lymphedema, stasis papillomatosis||Antibiotics, excision||NR||69,74,103|
|Leg/thigh||21 F, 18 M||47 years (2–75)||Plaque or mass (unilateral 70%), up to 71 cm or 38.2 kg||3 months to 43 years||Acid burn, cellulitis, hypothyroidism, linear morphea, lymphadenectomy, lymphangioma, morbid obesity, morphea, psoriasis, trauma (blunt), U-shaped (trapdoor) and curvilinear scars, vein stripping||Chronic obesity lymphoedematous mucinosis, elephantiasis nostras cutis, massive localized lymphedema, massive localized lipolymphedema pseudotumor, scar lymphedema, stasis papillomatosis, unilateral edema, verrucous and elephantoid lymphedema||Panniculectomy/resection, conservative wide resection||Improved/no recurrence persistence or recurrence 33%||53,54,68,69,72,73,76,93,94,97,99,100,103,105,106,108–112|
|Nose||1F, 11 M||63 years (34–82 years)||Enlargement, polypoid nodules, 11 cm, 2–25 cm||4.8 years (1–10 years)||Granuloma faciale, rosacea||Giant rhinophyma||CO2 laser, debulking||Improvement – majority||22–27|
|Penis||12 M||∼39 years (10–59)||Polyp, plaque, diffuse swelling, 4.1 cm, 2–7.5 cm||6 months to 10 years||Anogenital granulomatosis, cancer, cellulitis, chronic condom catheter use, Crohn’s disease, idiopathic, hidradenitis suppurativa, multiple sclerosis, paraphimosis, paraplegia||Lymphedematous fibroepithelial polyp, fibroepithelial polyp, lymphangioma||Excision||No recurrence 5, recurrence 2, persistence||16,17,21,48,50,66,90,113,115|
|Scrotum||14 M||40 years (11–58)||Enlargement (swelling), mass, or plaque (39–80 cm)||4 months to 36 years||Anogenital granulomatosis, diabetes mellitus, hidradenitis suppurativa, lymphogranuloma venereum, morbid obesity, penectomy and bilateral inguinal lymphadenectomy, phimosis, recurrent cellulitis, spina bifida, urinary tract infection||Genital lymphangioma, (giant) scrotal elephantiasis, scrotal lymphedema||Antibiotics, debulking surgery||Improved or no recurrence||48,69,77,94,102,104,107,113,114|
|Vulva||28 F||∼38 years (16–45)||Polyps, plaque, mass, 1–12 cm||Weeks to 4 years||Congenital lymphedema, Crohn’s disease, exogenous hormones, genital mutilation, hidradenitis suppurativa, lichen planus, hypertrophic, morbid obesity, pregnancy and vaginal delivery, Quadriplegia||Fibroepithelial stromal polyp, cellular pseudosarcomatous fibroepithelial stromal polyp, atypical myxoid fibroepithelial polyp, papillomatosis, lymphangiectases, cavernous lymphangioma||Local excision, vulvectomy||Improvement/no recurrence 70%, recurrence/persistence 30%||9–12,15,29,70,77,78,90,94,95,101|
For patients with whole-limb swelling, the most common presentation of lymphedema, evaluation includes careful history searching for prior surgical or radiation therapy for cancer and other risk factors for lymphedema, such as prior trauma to, or infection (cellulitis) of the affected limb.6,119 Physical and laboratory examination (e.g. circumferential measurements, bioimpedance, lymphoscintigraphy) focuses on differentiating signs of lymphedema from other causes of systemic or localized swelling such as cardiac or renal failure, protein losing conditions, lipedema, deep vein thrombosis, chronic venous insufficiency, myxedema, and cyclic or idiopathic edema.6 Most lymphedema patients are diagnosed clinically and/or by imaging and do not require biopsy to confirm the presence of lymphedema. However, based on this 4-year survey of skin biopsies, there exists a rare and small population of patients who have clinically unrecognized lymphedema that manifests either as a lymphedematous skin tumor or as diffuse involvement of a body site as a complication of pre-existing inflammatory, infectious or neoplastic disorders. The spectrum of tumorous lymphedema ranges from a solitary polyp to solid plaque that can develop papillomatosis, to a large, sarcoma-like mass. In this population, cancer and its treatment do not play a role, whereas local trauma because of tear or laceration predates the acquisition of the tumor in over half the cases. As the overwhelming majority of local trauma and surgical excisions are not associated with clinically persistent lymphedema (likely because of collateral lymphatic drainage), the nature of the injury to the lymphatics must play a role in the acquisition of localized lymphedema.
Transverse facial scars and S- and U-shaped scars can result in so-called scar lymphedema, which is differentiated from inflammatory edema by its placement on one side of a scar31,32,53 (Fig. 12). Scar lymphedema typically subsides in 6–8 months after injury; however, if the swelling persists past this point, this phenomenon has been attributed to the ‘trap-door’ effect (outward bulging of the skin circumscribed by the retracted scar) where fat is bunched up by bands of contracted scar tissue. Other mechanisms postulated for the ‘trap door’ effect include mechanical forces, fibrosis and lymph stasis. Recently, in a study assessing lymphatic drainage in scar lymphedema, no lymphatic flow could be shown bridging the scar in 8 of 11 patients with U-shaped or linear scars.53 In addition, no lymphatic channels could be found in Z-plasty flaps of two patients with multiple prior Z-plasty revisions to the limbs of curvilinear scars.53 These findings implicate lymphedema in the pathogenesis of persistent scar lymphedema and show that, in some cases, lymphatic drainage is not re-established across some types of scar. Therefore, specific types of skin injury can lead to loss of lymphatic drainage from localized areas of skin. Persistent localized lymphedema from such skin injuries can potentially progress to the end stage of lymphedema, elephantiasis. Based on our observations, skin inflammation, clinical or subclinical, probably plays a role in the development of localized elephantiasis.
Lymphedematous swelling can be broken into distinct stages:119, 129
- 1Stage 0 – latency: subclinical lymphedema due to impaired lymph transport
- 2Stage 1 – reversible: high protein, pitting edema (recedes with elevation); focal fibrotic alterations
- 3Stage 2 – spontaneously irreversible: brawny-hard, non-pitting swelling (does not recede with elevation); fibrosclerosis and adipocyte proliferation
- 4Stage 3 – elephantiasis: hard, non-pitting swelling, exaggerated skin folds, papillomatosis, hyperkeratosis; verrucous and papillated epidermal hyperplasia, fibrosclerosis and adipocyte proliferation
All stages of lymphedema show inflammatory changes that consist of increased numbers of capillaries and fibroblasts, dilated lymphatics, inflammatory – mostly macrophage infiltrates, expression of human leukocyte antigen-DR by epidermal and dermal constituents, and hyperproliferation of keratinocytes.118,130–132 In addition, decreased lymph flow (low output failure) results in impaired lymphocyte and Langerhans’ cell trafficking from skin to regional lymph nodes and impedes clearance of foreign antigens. These alterations make lymphedematous skin susceptible to infection, neoplasia and immune disorders.130,133 For progression to elephantiasis to occur, additional inflammatory insults or burdens superimposed on the existing immune deficiency of lymphedema appear crucial.119,131,134–136 Filariasis is the most common world-wide cause of lymphedema and provides a clinical example of the role of inflammation in the progression of lymphedema. Asymptomatic microfilaremia (absent host response) does not progress to amicrofilaremic, anti-filiarial antibody-positive lymphatic disease.135 In contrast to patients with symptomatic lymphatic filariasis, increasing frequency of episodes and duration of dermatolymphangioadenitis positively correlate with progression of lymphedema.134 Compared with surgically induced lower limb lymphedema, filarial lymphedema skin shows significantly more epidermal proliferation, denser inflammatory infiltrates, more numerous lymphangiectases and numerous macrophages (CD68+).131 Lack of clearance of filarial and bacterial antigens from and colonization of the lymphedematous skin, surface and deep (dermal) tissues, by commensal bacteria137 probably contributes to this environment of persistent, severe inflammation driving progressive limb enlargement and surface papillomatosis. Therapy against filaria with doxycycline leads to significant improvement in filarial lymphedema 138. Specifically, the mean stage of lymphedema in the doxycycline-treated patients was significantly lower compared with placebo patients, and this reduction of lymphedema stages was manifested as better skin texture, a reduction of deep folds, fewer deep skin folds, reduction in plasma levels of VEGF-C/sVEGFR-3, and a reduction in the number or dilated lymphatics.138 In this study’s cohort, those patients with a history of cellulitis, dense inflammatory infiltrates and lymphoid follicle formation (a sign of persistent antigen) had the largest tumors and were less likely to be helped by local excision. Furthermore, the presence of cysts and surrounding granulomas implicate keratin debris as another source antigen contributing to the progression of tumorous lymphedema. As not all patients with chronic inflammatory disorders such as hidradenitis suppurativa progress to lymphedema and elephantiasis, an underlying predisposition must exist that allows clinically apparent lymphedema to occur. As 85% of this cohort had abnormally high BMI, obesity is the most likely candidate to have created a state of latent lymphedema (subclinical, low output lymphedema).119
Morbid obesity is not only a cause or an exacerbating factor for numerous systemic diseases such as coronary artery disease, hypertension and diabetes mellitus. It is also a causative factor of numerous chronic skin diseases such as fibroepithelial polyps (acrochordons), acanthosis nigricans, pressure ulcers, intertrigo, plantar hyperkeratosis and lymphedema.139 Obesity and lymphedema are more than sum of two diseases.119 In morbid obesity, the lymphatics are overwhelmed by gross increase in adipose tissue that has mechanical and infectious consequences. Increased abdominal adipose tissue pushes the diaphragm above its normal position, impairing its movement and leading to decreased lymph flow. Decreased muscular function, peripheral vascular disease and mechanical obstruction of major lymphatic vessels also leads to decreased lymph flow. In addition, the large and numerous pendulous skin folds of obesity cause skin friction and maceration, which leads to intertrigo. The breakdown of skin barrier found in intertrigo and its warm moist environment allows secondary bacterial and yeast infections to occur. These secondary infections may well be a contributive factor in the development of massive localized lymphedema (sarcoma-like mass) arising on the trunk and extremities of morbidly obese individuals. All the patients in one series of massive localized lymphedema complained of chronic intertrigo.105
The muscles act as a lymph pump;140 thus, muscle paralysis would be expected to produce lymph stasis and predispose to lymphedema. In support of this supposition is the presence of quadriplegia in case 19 and a case of vulvar lymphedema,95 and paraplegia in most of the patients with penile lymphedematous fibroepithelial polyps.16,17 Condom catheter use was reported in the later cases. The pressure asserted by these condom catheters could have further decreased the lymphatic transport to the point where localized lymphedema could develop.16,17,21
Vulvar lymphedematous fibroepithelial polyps were the most common tumor in our series. Reports of vulvar fibroepithelial stromal polyps have many features in common with our series including recent pregnancy.9–11,15,28,29 All these polyps exhibited edematous to myxoid dermis, increased number of blood vessels, dilated lymphatics and numerous spindle, stellate and multinucleated cells similar to that found in our cases. Smooth muscle expression by the stromal cells was described for vaginal not vulvar tumors,10 which corroborates our results that show no smooth muscle or myofibroblast differentiation of the tumorous lymphedema stromal cells. However, cytologic atypia, and mitotic figures including atypical mitoses were not identified in our series.28 These later feature might be secondary to chronic irritation, ischemic injury or putative tumor progression facilitated by decreased immune surveillance found in chronic lymphedema.133
In addition to the requisite histologic features used to identify cases of lymphedema in this series, lymphedematous skin shows fragmentation and loss of mature elastic fibers, and increased numbers of FXIIIa+ and CD68+ dermal spindle, dendritic and multinucleated cells.7,26,97,118 This phenotype was also common to our series. Disruption or loss of elastic fibers, which help to maintain tissue form and structural integrity to lymphatic vessels,118 may underlie the pathogenesis of polypoid tumors, pendulous swellings and masses shown by lymphedematous tumors. Loss of elastic tissue in localized lymphedema has been described in a handful of cases.22,65,87,91 For example, Marzano et al.87 showed complete loss of elastic fibers in a rosacea patient who developed massive elephantoid eyelid lymphedema. Interestingly, obese patients may suffer edematous eyelids and the floppy eyelid syndrome. This syndrome is suspected to be the result of eyelid eversion during sleep;141 however, chronic lymphedema because of morbid obesity is another possibility. Upregulation of matrix-metalloproteinases (MMP) activity with subsequent fragmented elastic fibers has been proposed as the pathogenic mechanism.142,143 Increased expression of MMP has also been described in chronic lymphedema and an experimental mouse model of lymphedema.118,132
Currently, there is no consensus on how to mange chronic (whole limb) lymphedema. Compressive garments, intensive bandaging and lymphatic massage serve as the foundation for therapy.6 For patients unresponsive to these conservative methods, surgery with excision or debulking, microsurgical anastomoses and circumferential suction-assisted lipectomy can be used;6 the latter approach appears to hold promise for long-term relief of symptoms.144 Phymatous rosacea provides a working model for the treatment of localized lymphedema. Surgical therapy is mainstay in the treatment of phymatous rosacea, usually involving a combination of partial thickness skin excision and dermaplaning followed by dermabrasion.127 Laser techniques, cryosurgery and other modalities can also be used.127 In this series of localized lymphedema, the majority of lymphedematous tumors were cured with excision, and those that recurred or progressed were associated with factors known to aggravate lymphedema: obesity, cellulitis, signs of persistent inflammation such as lymphoid follicles and follicular cysts – the presumptive antigenic site and/or source of keratinous debris for chronic inflammation. In addition to excision or debulking, medical therapy targeting the underlying inflammatory process, to quell chronic, severe inflammations such as antibiotics for cellulitis and antibiotics plus isotrentoin for rosacea will probably be required to control refractory, localized tumorous lymphedema, in addition to excision or debulking.
Decreased local immunosurveillance occurs in lymphedematous skin increasing the risk for malignancy.133 For example, basal cell carcinomas occur significantly more frequently in rhinophyma (lymphedematous rosacea) than normal nasal skin,145 and squamous cell carcinoma has been reported in isolated penile lymphedema.66 Therefore, the suspicion for skin cancers should be elevated in areas of longstanding lymphedema that develop tumors.
Localized lymphedema should be considered in the etiology of skin tumors when assessing a polyp, plaque, swelling or mass showing dermal edema, fibrosis and dilated lymphatics on biopsy. A combination of lymph stasis promoting factors produces circumscribed elephantiasis. For example, trauma transecting lymphatic drainage pathways to a region of subclinical (latent) lymphedema because of obesity will be responsible for the development of localized clinical lymphedema (reversible and spontaneously irreversible stages). Additional episodic and/or chronic inflammatory insults to this region caused by bacterial cellulitis or persistent inflammation directed at the contents of follicles and cysts from follicular disruption from disorders such as hidradenitis suppurativa, will promote progression to localized elephantiasis. As the prevalence of lymphedema in association with inflammatory dermatoses and neoplasms is unknown, we recommended reporting its presence in pathology reports. This data may prove invaluable in determining the impact of lymphedema on the development of cutaneous infections, autoimmune disorders and neoplasia.133
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