András Kovács L.¹, Zsolt Kádár¹, Éva Varga¹, Iván Péter¹, Mehdi Moezzi¹, Imre Schneider¹, Endre Kálmán², Krisztián Molnár³, Dalma Várszegi¹ Department of Dermatology¹, Department of Pathology², Department of Radiology³ University of Pécs, Medical School, Pécs, Hungary

1. CLINICA DERMATOLOGICA
PÉCS
HUNGARIA
DIFFERENTIAL DIAGNOSIS OF LEG ULCERS
- ULCERS OF RARE ETIOLOGIES
András Kovács L.¹, Zsolt Kádár¹, Éva Varga¹, Iván Péter¹, Mehdi Moezzi¹,
Imre Schneider¹, Endre Kálmán², Krisztián Molnár³, Dalma Várszegi¹
Department of Dermatology¹, Department of Pathology², Department of Radiology³
University of Pécs, Medical School, Pécs, Hungary

2. • Aim : chronic wounds without a tendency to heal present a serious public
health and economic issue. With the case reports the authors present ulcers
of rare etiologies, emphasising the importance of performing differential
diagnosis before treatment.
• Methods : in 2012 the authors have treated 268 patients with leg ulcer in
their department of dermatology. In cases of chronic, non-healing ulcers
with an atypical wound and medical history histological examination was
performed in order to establish a correct diagnosis. From the new patients
treated in 2012 the authors present 7 cases of leg ulcers, including 6
various, rarely occuring ulcers.

3. Case 1.: ulcerative basalioma
• female patient, 91 years old
• approx. 2,5 years history of ulcers resistant to conservative therapy on the medial surface of the
middle and lower third of the left leg
• solar damage of the skin: solar keratoses, skin tumors (basal cell carcinoma) of the face and chest
• ulcerative malignant tumor of the skin suspected as the possible cause of the atypical leg wounds
• sampling excision from the border of the leg ulcers – histological examination
• Diagnosis: ulcerative basal cell carcinoma, nodulocystic and infiltrative type
• Therapy: extirpation of the tumors
basalioma- nodulocystic type
basalioma – infiltrative type
basalioma

4. Case 2.: leg ulcer - basalioma
metaplastic subtype
• female patient, 82 years old
• approx. 3 years history of ulcer resistant to conservative
therapy on the dorso-lateral surface of the lower third of the
right leg with a size of 3x2 cm
• angiological examination: varicosity, chronic venous
insufficiency
• skin cancer has been taken into consideration as the
possible cause of the atypical wound
• sampling excision from the border of the ulcer – histological
examination
• Diagnosis: basal cell carcinoma – metaplastic subtype
• Therapy: extirpation of the tumor, covering with skin graft
Histology:
• ulcer covered by crust
• infiltrative tumor forming cellular nests
• the cells do not palisade
• the nuclei are vesiculated
• a central nucleolus is present
• the cytoplasm is mildly vacuolized and cubic

5. Case 3.: squamous cell carcinoma
on the base of chronic leg ulcer
• female patient, 71 years old, post-thrombotic syndrome on the
left leg, varicectomy 3x, chronic venous insufficiency
• recurrent ulcer, above the left inner ankle since the 1980s
• 2x plastic surgery treatment of the ulcer – in the 1990s
• 1998 – healing of the ulcer; 2009 – recurrency of the ulcer,
conservative treatment, no tendency to heal
• 2012 – sampling excision for histological examination of a 6x4 cm
verrucous, hyperkeratotic tissue developed on the tibial side of
the ulcer
• Diagnosis: carcinoma planocellulare partim keratosum invasivum
cutis, Grade 2.
• staging examinations (CT - chest, abdomen, pelvis) negative
• Therapy: extirpation of the ulcer and tumor, super selective
cytostatic treatment administered into the external iliac artery,
oncological management
←
←
←←
well differentiated
squamous cell carcinoma

6. Case 4-5.: pyoderma gangrenosum
• male patient, 70 years old, a rapidly progressive ulcer with a livid-purple
coloured margin has developed on the left leg in the region of the Achilles
tendon following a minor trauma (chafing from his shoes)
• male patient, 52 years old
• progressive ulcer developed 4 months
ago following an insect bite
• no tendency to heal
• vascular surgery: compensated
circulation, no sign of trophic disorder
• sampling excision from the ulcer
• Diagnosis: pyoderma gangrenosum
• ANA, ENA, ANCA, ASCA screen: negative
• Therapy: systemic steroid sine effecto;
4 cycles of cyclophosphamide – healing
excavated, deep ulcer, continuity
of the Achilles tendon has broken
• sampling excision from the ulcer
• Diagnosis: pyoderma gangrenosum
• ANA, ENA, ANCA, ASCA screen: negative
• CA-15-3: (28), CA-19-9: (72,8) positive
• chest CT-scan: esophageal stenosis
• abdominal CT- scan: negative for tumor
• patient would not undergo gastro-
enterological examination
• Therapy: methylprednisolone, colchicine,
necrectomy, transplantation, healing
ulcer with extensive necrosis and massive
granulocyte reaction
• Necrosis and inflammatory infiltration
consisting of granulocytic fields can be
found deep under the ulcer.
• secondary vascular damage
• necrosis of the vessel walls

7. Case 6.: ulcer associated with lichen
sclerosus et atrophicus
• female patient, 61 years old
• skin lesions ongoing for the last 2 years
• sensitive, infiltrated, haemorrhagic, partially bullous plaques,
ulcerations, scars on the extensor surface of the legs
• atrophic hypopigmented macules and plaques with the various
sizes on the extensor surface of the arms, the chest, the
abdomen, around the hip and in the genitofemoral area
• sampling excision from the lesions
• histological examination:
hyperkeratosis, atrophic epidermis, sclerotic dermis, mild basal vacouli -
zation, hypocellular subepithelial zone, below a band-like lymphoid
reaction can be seen, no sign of vasculitis
• Diagnosis: lichen sclerosus et atrophicus

8. Case 7.: ulcer associated with
scleroderma - rheumatoid arthritis
overlap syndrome
• female patient, 58 years old, locomotor symptoms since 1987,
polyarthritis – rheumatologic management
• coxarthrosis l.u., st.p. impl. TEP coxae l.d. (2002)
• bilateral plantar ulcers – osteomyelitis – amputatio dig. ped II.
l.u. (2003)
• ulcer without a tendency to heal on the lateral side of the right
leg, spreading over the foot, since 2005
• nearly unable to walk, severe deformities and degenerative
alterations of the small and large joints
• ulnar deviation and flexion contracture of the fingers on the
hands, ankylosis
• feet: III – IV. mallet finger, hallux valgus, II. finger removed

9. angiography: no sign of arterial stenosis,
early venous filling on the right leg -
sign of chronic venous insufficiency
• immunological management since 2003
• immunoserology: ANA screen: 69,2 U/ml, ENA screen: 10,2 U/ml, Scl-70: 26,9 U/ml, RF IgA: 47,9
U/ml, RF IgM: 275,8 IU/ml, RF IgG: 146,5 U/ml
• rheumatoid arthritis; sclerodactylia; capillary microscopy (Maricq II pattern)
• Diagnosis: rheumatoid arthritis – systemic sclerosis overlap syndrome
• Therapy: depo steroid, non-steroid anti-inflammatory medication, chloroquine, sulfasalazine,
methotrexate, leflunomide, methylprednisolone, cyclophosphamide, pentoxifylline,
fentanyl; currently the underlined
• Etiology of the ulcer is multifactorial: primary disease, inactivity, limb deformity, chronic venous
insufficiency
Histological examination:
• epithelial hyperplasia, elastic fiber degeneration
• chronic inflammatory cell reaction, scarification
• vascular profiferation, no sign of vasculitis

10. • Results: histological examination of ulcers without a tendency to heal performed
based on the clinical picture proved to be beneficial in establishing the correct
diagnosis.
• Histological examination of the ulcer is suggested:
atypical location; atypical wound; unknown etiology; resistance to therapy;
change in the clinical presentation (ulcer base and margin: hyperkeratosis,
abnormal granulation, palisade-like ulcer margin).
• Conclusion: The primary aim of modern wound management is determining the
disease causing the ulcer, treating the condition inducing the healing disorder,
namely causal therapy. In cases of chronic ulcers resistant to therapy, ulcers of
rare etiologies, such as malignancies, pyoderma gangrenosum or ulcers
associated with autoimmune diseases, also have to be considered during
differential diagnosis. Establishing the correct diagnosis as early as possible is
substantial regarding the fate of the patient, the chosen therapy, the effectiveness
and cost of the treatment and the healing of the chronic wound.