Initial presentation of stasis dermatitis mimickingsolitary lesions: A previously unrecognized

clinical scenario

Joshua Weaver, MD,a and Steven D. Billings, MDa,b

Cleveland, Ohio

Background: Stasis dermatitis is a common skin condition secondary to chronic venous insufficiency.Characteristic dermatologic changes in well-developed disease include bilateral erythematous, scaly, andslightly discolored papules and plaques on the lower legs. Earlier signs, such as prominent superficial veinsand pitting ankle edema, are well known. Early recognition of signs and appropriate diagnosis can lead totimely treatment that can prevent painful complications, such as leg ulcers which are at risk fordevelopment of squamous cell carcinoma.

Objective: Herein we describe a yet unrecognized early sign of venous dermatitis—a solitary lesion, somemimicking neoplastic processes.

Methods: Thirty-seven cases of stasis dermatitis submitted with the clinical diagnosis of a solitary lesion wereidentified. Thirty-three had no clinical history of venous insufficiency. All cases of stasis dermatitis presentingfor the first time as a solitary lesion were reviewed retrospectively both clinically and pathologically.

Results: Squamous cell carcinoma was most commonly suspected (33%), followed by basal cell carcinoma(24%), and a variety of other solitary lesions. The histopathology was characteristic of stasis dermatitis in allcases with absent or mild spongiosis (82%), variable acanthosis and dermal fibrosis, and proliferation ofpapillary dermal thick-walled vessels were prominent (2-3+) in nearly all cases ( $ 90%) along withhemosiderin-laden macrophages and extravasated red blood cells ( $ 95%).

Limitations: The study is limited by its retrospective nature and absence of clinical images on all cases.

Conclusion: Stasis dermatitis may present as a solitary lesion mimicking a neoplasm. Early recognition ofstasis dermatitis can lead to appropriate treatment and possibly prevent further morbidity. ( J Am AcadDermatol 2009;61:1028-32.)

INTRODUCTION

Stasis dermatitis is a cutaneous manifestationand marker of increased venous pressure ofthe lower extremities. It is a common condi-

tion affecting predominantly middle-aged to elderly

From the Departments of Anatomic Pathologya and Dermatology,b

Cleveland Clinic.

Funding sources: None.

Conflicts of interest: None declared.

A portion of this work was presented at the 45th Annual Meeting of

the American Society of Dermatopathology in San Francisco, CA.

Reprint requests: Steven D. Billings, MD, Department of Anatomic

Pathology/L25, The Cleveland Clinic. 9500 Euclid Ave, Cleveland,

OH 44195. E-mail: billins@ccf.org.

0190-9622/$36.00

ª 2009 by the American Academy of Dermatology, Inc.

doi:10.1016/j.jaad.2009.04.025

1028

individuals that usually presents as erythematous,slightly yellow to brown pigmented patches over thebilateral lower legs with or without conspicuousvaricose veins. Most cases are caused by insufficientdeep venous system valves preventing proper returnof blood to the central circulation through themuscular pumping action of the lower legs. Venousvalvular insufficiency can be caused by prior throm-bophlebitis or congenital fragility. Pregnancy,obesity, and other causes of increased abdominalpressure can also lead to chronic venousinsufficiency.

Abbreviations used:

H&E: hematoxylin-eosin (stain)PAS: periodic acideSchiff

J AM ACAD DERMATOL

VOLUME 61, NUMBER 6

Weaver and Billings 1029

Stasis dermatitis can be associated with signifi-cant complications. Long-standing stasis dermatitisaccounts for approximately half of chronic legulcers.1 Chronic venous leg ulcers lead to significantdecreases in the quality of these patients’ livesthrough physical pain, negative emotions, andmonetary loss.2 Development of squamous cellcarcinoma in long-standingchronic venous ulcers isanother risk that patientswith stasis dermatitis face.Therefore diagnosis of stasisdermatitis early in the pro-cess is important as it mayallow for earlier interventionto potentially prevent thesecomplications.

Although most cases arediagnosed clinically throughhistory and physical find-ings, a biopsy is often em-ployed if there is no clearhistory and physical findingsare atypical. Histologically,stasis dermatitis demon-strates a lobular proliferationof thick-walled blood ves-sels in the papillary dermiswith a variable proportion ofother features including ex-travasated red blood cells,hemosiderin-laden macrophages, and dermal fibro-sis.3 The variation of dermal changes is thought tobe related to the age of the lesion with prominentfibrosis and siderophages in long-standing disease.The distribution of siderophages can help distin-guish stasis dermatitis from pigmented purpuricdermatosis, with the macrophages present through-out the dermis in the former, but only in the upperone third of the dermis in the latter.3 Variablechanges of the epidermis occur as well, such asspongiosis, parakeratosis, and development of acrust. The variation of these changes depend onwhether there is an overlying eczematous derma-titis thought to be caused by the oversensitivenature of the skin in stasis dermatitis—so-called‘‘autoeczematization’’.

The initial stage of venous insufficiency is cus-tomarily edema of the lower legs. However, we havenoted many cases of stasis dermatitis on skin biopsyspecimens submitted with differential diagnosesconsistent with a solitary disease process. Hereinwe report a series of cases describing a previouslyundocumented phenomenon of stasis dermatitispresenting in an initial evaluation clinically as a

solitary lesion and in some cases mimicking a neo-plastic process.

METHODSA computerized search through the pathology

archives at the Cleveland Clinic was performedusing the keywords ‘‘stasis dermatitis’’ in the diag-

nosis field between Jan 1,1992 (time when clinicaldata from the pathology req-uisition form were added tothe database) and March 25,2008. All electronic andphysical clinical charts wereavailable for review docu-menting at the initial visit:presence or absence of ahistory of stasis dermatitis,presence or absence of ahistory of another concur-rent or metachronous ecze-matous process, evidence ofpedal edema on physicalexamination, symptoms ofdependent ankle swellingduring prolonged standing,clinical presentation and de-scription of the lesion, age,sex, and the clinical differ-ential diagnosis. Availablefollow-up information

through the electronic and physical clinical chartswas reviewed to document the development ofclassic broader patches of stasis dermatitis. Forinclusion in the study, the cases had to clinicallypresent as a solitary lesion, and the patient couldnot have an already established diagnosis of stasisdermatitis or chronic vascular insufficiency.

Cases meeting the selection criteria were reviewedfor histological changes including the degree ofacanthosis, spongiosis, parakeratosis, proliferationof vessels, dermal fibrosis, presence of hemosiderin-laden macrophages, thickness of vessels, and hemor-rhage based on a scale from +1 to +3 (mild, moderate,or severe). Additionally, the presence or absence ofspongiotic vesicle and crust formationwasnoted.Anyavailable additional special stains (eg, Gomori meth-enamine silver) and recuts were also reviewed. Inaddition, two deeper hematoxylin-eosinestained(H&E) sections were performed to rule out possiblepreviously unrecognized preneoplastic/neoplasticprocesses left in the paraffin block that could other-wise explain the presence of a solitary lesion.Furthermore, all cases with H&E findings of intraep-idermal neutrophils, intraepidermal lymphocytes, or

CAPSULE SUMMARY

d Stasis dermatitis can commonly (7%)manifest early as a solitary lesion beforemore typical clinical diagnostic changesdevelop.

d These solitary lesions most commonlyclinically mimic neoplasms, includingSCC (33%) and BCC (24%).

d The histopathology of stasis dermatitisconsists predominantly of dermalchanges including lobular proliferationof thick-walled papillary dermal bloodvessels with evidence of dermalhemorrhage. Epidermal changes areusually mild.

d Early recognition of this clinical scenarioof stasis dermatitis initially presenting asa solitary lesion can lead to appropriatetreatment and prevent further morbidity.

J AM ACAD DERMATOL

DECEMBER 2009

1030 Weaver and Billings

Table I. Demographics, clinical features, and diagnosis

Patient No. Sex Age (y) Clinical morphologic description (if available) Clinical diagnosis

1 F 59 15-mm scaly plaque w/ central erosion on R lower leg ISK2 F 42 12-mm scaly nummular patch on L pretibial area SCC3 F 49 7-mm scaly erythematous papule on L pretibial area BCC4 F 67 9-mm erythematous atrophic plaque w/ smooth surface on R medial malleolus ISK5 M 61 Erythematous red firm papule on L lower leg GA6 F 59 2-cm erythematous atrophic plaque w/ minimal circumferential scale w/

adjacent hypopigmented scar on R pretibial legScar

7 M 64 7-mm erythematous scaly patch on L medial lower leg ISK8 M 79 Small flesh-colored flat plaque on R leg BCC9 M 76 Thick keratotic area on lower leg SCC

10 F 52 8-mm erythematous scaly papule on R mid anterior pretibial leg BCC11 F 64 6-cm ulcer with surrounding mild erythema on R lower anterior leg PG12 F 82 Not available GA13 F 89 L posterior leg ulcer SCC14 F 77 Erythematous papule on R lower leg SCC15 F 60 8-mm erythematous scaly irregular plaque on R lateral calf SCC16 M 57 1-cm lesion w/ central erosion on L leg Nevus17 F 53 2-cm, somewhat eczematous, erythematous irregular patch on L pretibial area BCC18 M 87 Erythematous plaque w/ ulceration on R lower leg SCC19 F 75 13-mm erythematous shallow plaque on L pretibial leg GA20 F 57 Not available BCC21 F 66 3-cm shiny atrophic plaque, slightly hypopigmented on L pretibial leg Scar22 M 64 Not available Kaposi sarcoma23 F 78 Erythematous scaly plaque on L lateral calf BCC24 M 74 Not available AK25 F 84 2.3-cm violaceous crusted plaque on L medial ankle SCC26 F 68 Not available BCC27 F 79 Not available SCC28 F 66 2-cm erythematous plaque w/ scale on R lower leg BCC29 M 46 Erythematous plaque with central ulceration and crust on R lower leg PG30 F 76 Not available SCC31 M 56 Not available Scar32 M 61 5-mm papule on L ankle SCC33 M 65 18-mm firm erythematous scaly nodule on L lower leg SCC

AK, Actinic keratosis; BCC, basal cell carcinoma; F, female; GA, granuloma annulare; ISK, irritated seborrheic keratosis; L, left; M, male; PG,

pyoderma gangrenosum; R, right; SCC, squamous cell carcinoma.

impetiginized serum crust were evaluated with aperiodic acideSchiff stain, if fungal stains were notperformed during initial evaluation, in order to ruleout the possibility of superficial dermatophytosis.

The study was approved by the institutionalreview board of the Cleveland Clinic.

RESULTSThe initial query identified 483 cases with the

primary diagnosis of stasis dermatitis. Of the initial483 cases, 37 patients presented with a clinicaldiagnosis of a solitary lesion. Four patients with ahistory of chronic venous insufficiency were ex-cluded from the study, leaving 33 cases for the study,representing 7% of all cases of stasis dermatitis (TableI). None of the remaining 33 patients had history of apreviously diagnosed nummular eczema or irritant

dermatitis prior to the biopsy of the lower leg solitarylesion.

Demographically, this under-recognized eventoccurred in the usual setting for stasis dermatitis:the lower extremities of older adults (average age, 66years-old), with a female predominance (female:-male, 1.8). Eleven cases (33%) had evidence of pedaledema on initial physical examination; however,only 3 patients (9%) were elicited to describe symp-toms of ankle swelling after prolonged standing.Detailed clinical descriptions were available on asubset of cases (n = 29). The most common presen-tation was a single erythematous plaque on the lowerportion of the leg, affecting either lower extremitywith equal frequency (right:left, 0.8) (Fig 1). Theexact location of the lesions on the lower legs couldnot be ascertained in the majority of cases due to the

J AM ACAD DERMATOL

VOLUME 61, NUMBER 6

Weaver and Billings 1031

lack of additional detail provided in the clinical notesduring the retrospective chart reviews. Only 3 caseswere specifically mentioned to have occurred on themedial malleolus, which is the classic location of theinitial onset of stasis dermatitis; however, this num-ber is likely an underestimation because of thelimitations of this retrospective study. The averagesize of the lesion was 1.6 cm. Out of a total of 21 casesdescribed as a papule, plaque, nodule, or patch; themost common presentation was a plaque (57%),followed by papule (24%), patch (14%), and nodule(5%). Fifty-six percent of cases presented with someerythema, 40% described scaling, while only 24%were eroded.

The most common clinical diagnosis was squa-mous cell carcinoma (33%) followed by basal cellcarcinoma (24%). Another 3 (9%) cases were thoughtclinically to be consistent with a granuloma annulareand another 3, irritated seborrheic keratosis. Otherclinical differential diagnoses included scars, pyo-derma gangrenosum, actinic keratosis, Kaposi’s sar-coma, nevus, and a neoplasm, not otherwisespecified.

The histopathology of all the cases demonstratedthe classical morphologic picture of stasis dermatitiswith variable acanthosis and mild spongiosis of theepidermis and underlying proliferation of thick-walled blood vessels in the papillary dermis withdeposition of hemosiderin and extravasation of redblood cells (Fig 2). Spongiotic change in the epider-mis was absent or mild (0 or 1+) in 27 cases (82%),and spongiotic vesicles were never demonstrated.Parakeratosis was present in roughly half of the cases(58%), which correlated with the clinical impressionof a scale also approximately half of the time. Aserum crust was only identified in 5 cases (15%). Thecharacteristic lobular proliferation of thick-walled

Fig 1. The most common clinical presentation of stasisdermatitis mimicking a solitary lesion was a single ery-thematous plaque on the lower portion of either leg.

blood vessels in the papillary dermis was alwayspresent; in the vast majority of the cases ([90%), thisfinding was moderate to marked (2-3+). Evidence ofhemorrhage including extravasated erythrocytes,hemosiderin deposition, and siderophages wereessentially always present ([95%). Some dermalfibrosis was present in all cases, but in variableproportions.

All recuts or levels performed at the time oforiginal diagnosis (n = 6; 18%) and all subsequentdeeper levels performed (n = 33; 100%) showedsimilar histologic findings as the original H&E slideswith no evidence of an additional process that couldexplain a localized lesion. Special stains (Gomorimethenamine silver, PAS, Steiner, Gram, andTwort’s) for microorganisms were performed duringthe initial evaluation on 9 of the cases (27%). All werenegative for fungal or bacterial organisms. Six casesrequired additional PAS stain for the histopathologicfindings of intraepidermal neutrophils, intraepider-mal lymphocytes, or impetiginized serum crust torule out dermatophyte infection. None of the casesshowed evidence of fungal forms on PAS stain. Only

Fig 2. A, Skin biopsies of all cases demonstrated classicalmorphologic picture of stasis dermatitis with mild acan-thosis and spongiosis of the epidermis and underlyingproliferation of thick-walled blood vessels in papillarydermis. B, Evidence of hemorrhage including extravasatederythrocytes, hemosiderin deposition, and siderophageswere essentially always present. (A and B, Hematoxylin-eosin stain; original magnifications: A, 3100; B, 3400.)

J AM ACAD DERMATOL

DECEMBER 2009

1032 Weaver and Billings

one case had an iron stain performed, which waspositive for hemosiderin within macrophages.

Follow-up clinical data were available for 31 of 33patients (94%) and demonstrated that 64% (14/22) ofpatients undergoing biopsy during 2004 and earlierdeveloped classic broader patches of stasis dermati-tis, whereas only 11% (1/9) of patients undergoingbiopsy during 2005 and since have currently devel-oped classic findings of stasis dermatitis.

DISCUSSIONStasis dermatitis caused by chronic venous insuf-

ficiency is a common condition that affects olderindividuals. The diagnosis is typically straightfor-ward and made on routine history and physicalexamination by identifying the usual dermatologicmanifestations—pruritic bilateral scaly erythematouspapules and plaques located on the lower third ofthe legs. Hyperpigmentation and hair loss may alsobe associated with the above findings. The hyper-pigmentation is usually a yellow-brown discolor-ation thought to be secondary to the hemosiderindeposition from extravasated red blood cells whichis then engulfed by dermal macrophages. In aminority of cases melanin in the form of dermalmelanophages and melanocytes have been impli-cated in contributing to the hyperpigmentation ofstasis dermatitis.4 The pigment incontinence may beexplained by resolution of a concurrent eczematousprocess; so-called autoeczematization which hasbeen described in this population. Initial signs beforethe characteristic lower leg skin changes includecongestion and dilation of the saphenous vein withfibrosis and pitting edema of the medial aspect of theankle and lower shins.5

Early diagnosis and appropriate treatment withcompression therapy in combination with patienteducation can help prevent the development ofpainful and difficult-to-treat venous stasis ulcersand therefore decreases the risk of development ofan ulcer-associated malignancy.6-9

Herein we have demonstrated the rare occurrenceof stasis dermatitis presenting as a solitary lesion asan initial manifestation before more typical clinicallydiagnostic changes. This early manifestation of stasisdermatitis accounts for 7% of all cases of stasisdermatitis in our clinical material. Importantly, thepatients had no history of chronic venous insuffi-ciency; therefore the solitary lesion frequently mim-icking a neoplasm was the initial presenting sign ofdisease. Interestingly, 64% of patients (14/22) withfollow-up longer than 4 years had already pro-gressed to a more definitive clinical picture withthe development of classic broad patches of stasisdermatitis, whereas only 11% of patients (1/9) with

less extensive follow-up had undergone the sameprocess. These findings suggest that a relatively long(4 years) period of time is required for the solitarypatch of stasis dermatitis to progress to a moredefinitive clinical picture. The remaining 8 patientswithout significant progression of their stasis derma-titis are most likely still at risk of developing a classicclinical picture of stasis dermatitis down the line.Therefore the evidence supports the findings thatstasis dermatitis can initially present as a solitarylesion with or without other classic signs or symp-toms of chronic venous insufficiency; furthermore asignificant subset of these patients go on to developmore classic broad patches of typical stasis changeson their legs.

As it is well-known that patients with a long-standing history of stasis dermatitis with associatedulcers are at risk of developing squamous cellcarcinoma and rarely basal cell carcinoma,7-9 der-matologists and dermatopathologists should also beaware that stasis dermatitis may clinically mimicneoplasms. Furthermore, the histopathology ofstasis dermatitis has not been extensively describedin the literature. This series emphasizes that thedermal changes including the lobular proliferationof thick-walled papillary dermal blood vessels andevidence of dermal hemorrhage are the essentialfindings in stasis dermatitis. Epidermal changes areusually mild in the lesions clinically mimickingneoplasms.

REFERENCES

1. James WD, Berger TG, Elston DM. Andrews’ Diseases of the skin

clinical dermatology. 10th ed. Philadelphia: Saunders Elsevier;

2006. p. 845-7.

2. Phillips T, Stanton B, Provan A, Lew R. A study of the impact of

leg ulcers on quality of life: financial, social, and psychologic

implications. J Am Acad Dermatol 1994;31:49-53.

3. Weeden D. Skin pathology. 2nd ed. Edinburgh: Churchill

Livingstone; 2002. p. 112.

4. Kim D, Kang WH. Role of dermal melanocytes in cutaneous

pigmentation of stasis dermatitis: a histopathological study of

20 cases. J Korean Med Sci 2002;17:648-54.

5. Worley CA. ‘It hurts when I walk:’ venous stasis disease—differ-

ential diagnosis and treatment. Dermatol Nurs 2006;18:582-3.

6. Erickson CA, Lanza DJ, Karp DL, Edwards JW, Seabrook GR,

Cambria RA, et al. Healing of venous ulcers in an ambulatory

care program: the roles of chronic venous insufficiency and

patient compliance. J Vasc Surg 1995;22:629-36.

7. Baldursson B, Sigurgeirsson B, Lindelof B. Leg ulcers and

squamous cell carcinoma. An epidemiological study and a

review of the literature. Acta Derm Venereol 1993;73:171-4.

8. Baldursson BT, Hedblad MA, Beitner H, Lindelof B. Squamous

cell carcinoma complicating chronic venous leg ulceration: a

study of the histopathology, course and survival in 25 patients.

Br J Dermatol 1999;140:1148-52.

9. Combemale P, Bousquet M, Kanitakis J, Bernard P. Malignant

transformation of leg ulcers: a retrospective study of 85 cases.

J Eur Acad Dermatol Venereol 2007;21:935-41.