Mimics in Surgical Pathology
Dr. Sunil Lakani
Dr. Salam Al-Sam
Case 3 -
Pseudoepitheliomatous Hyperplasia Mimicking Squamous Cell Carcinoma in Association with a CD30+ Lymphoproliferative Disorder
Dr E. Jaime Calonje
St John's Institute of Dermatology
St Thomas' Hospital, London, UK
Male, 77 years old. The patient presented with an eight week history of a rapidly enlarging,
non-painful, ulcerated, nodule on left side of abdomen. Initially was the size of a pea. No response to
treatment with antibiotics and topical steroids. No purulent discharge but bleeding after trauma. On
examination, there was a 2 x 2 cm friable, fleshy, mobile, ulcerated crusted nodule with surrounding
erythema on left abdomen. No other cutaneous lesions were found and there was no lymphadenopathy.
Clinical diagnosis: ?Keratoacanthoma. ?Squamous cell carcinoma.
Further investigation after biopsy.
Normal full blood count, renal function tests and live function tests.
CT scan of the trunk and pelvis: anterior small mediastinal lymph node and a small pre-carinal lymph
Case 3 - Figure 1
Ulcerated nodule with a squamoproliferative lesion associated with the epidermis and the infundibular
portion of the hair follicles. In the surrounding dermis there is a prominent, fairly polymorphic
infiltrate. In the epidermis and hair follicles there are strands and lobules of pale keratinocytes with
an endophytic growth pattern and focal keratinisation. The keratinocytes in the proliferation are fairly
homogenous with some degree of cytological atypia that tends to be mild. The lobules and strands of
squamous epithelium appear to be infiltrating the dermis. In areas, some nests of keratinocytes display
cystic change and there is exocytosis of neutrophils with formation of microabscesses. The infiltrate
around the squamous proliferation is dense and consists of neutrophils, eosinophils, mature round
lymphocytes and sheets of large atypical lymphoid cells with hyperchromatic nuclei, one or more nucleoli
and pink cytoplasm.
Immunohistochemical stains reveal the following phenotype in the large dermal lymphoid cells: CD2,
CD3, CD4 & CD5: positive. CD7: Focal loss of expression. CD30: Diffuse cytoplasmic and dot-like
perinuclear positivity. EMA and ALK-1: negative.
Pseudoepitheliomatous hyperplasia mimicking squamous cell carcinoma in association with a CD30+
lymphoproliferative disorder (CD30 positive anaplastic large cell lymphoma)
Primary cutaneous anaplastic large cell lymphoma
- Adults 7th decade
- M:F 2-3:1
- Solitary or localised nodules/tumours
- Multifocal lesions ~20%
- Extracutaneous dissemination to regional lymph nodes ~10%
- No preceding LyP, MF or other CTCL
- 75% or more of the cells in the infiltrate are CD30+ cells
- Immunophenotype: usually CD4+ T-cell phenotype
- Most cases are ALK-1 negative (absence of t(2;5)
- ALK-1 +ve: usually indicates cutaneous involvement by systemic
- In systemic cases EMA tends to be positive in tumour cells
- Prognosis of primary cutaneous CD30 positive anaplastic large cell
lymphoma: 5 year survival >90%
- Management: Excision/radiotherapy/chemotherapy
Distinction between CD30 positive anaplastic large cell lymphoma and LyP can only be made based on
very close clinicopathological correlation.
- Now regarded as a CD30 positive lymphoproliferative disease
- Chronic, self healing
- 4-5th decade, rarely children
- M:F 1.5:1
- Trunk, limbs
- Crops of necrotic papules or nodules
- 3-12 weeks to emerge
- Atrophic scarring
- 20% associated with another type of lymphoma (cutaneous T cell
lymphoma, Hodgkin's disease)
- Three histological types of lymphomatoid papulosis have been
described: LyP type A: (80% of cases): clusters of large CD30+ anaplastic cells with reactive
lymphocytes, neutrophils and/or eosinophils in the background. LyP type B: (10% of cases): shows an
epidermotropic infiltrate, has few CD30 positive cells and mimics cutaneous T cell lymphoma. LyP type C:
(10% of cases): shows a monotonous population of large CD30+ in sheets.
Pseudoepitheliomatous hyperplasia may be seen in 28-55% of CD30+ anaplastic large cell lymphomas and
in a smaller percentage of cases of lymphomatoidc papulosis. The degree of hyperplasia is variable but
may be quite prominent as to closely mimic a squamous cell carcinoma. This is particularly true in large
lesions of anaplastic large cell lymphoma. In patients that present with multiple lesions of anaplastic
large cell lymphoma, the differential diagnosis in cases with pseudoepitheliomatous hyperplasia is not
difficult. The main problem arises in patients presenting with a single tumour like in our case. The
problem may be further compounded by the fact that many clinicians tend to perform very small diagnostic
biopsies nowadays. If the biopsy is too superficial and if particular attention is not paid to the
dermal infiltrate, this may result in a misdiagnosis of squamous cell carcinoma and the therapeutic
approach will be wrong. It is also always important, particularly in the case of small samples to play
very close attention to the clinical information. Cutaneous squamous cell carcinomas almost always occur
in the background of sun-damaged skin in elderly patients. If a diagnosis of a cutaneous squamous cell
carcinoma is been considered in a small sample from a site not displaying sun damage, it may be crucial
to defer the diagnosis and to request a further larger specimen. This not only applies to
pseudoepitheliomatous arising in large cell anaplastic lymphoma but to other conditions associated with
The presence of large number of dermal atypical lymphoid cells in the background of
pseudepitheliomatous hyperplasia allows easy distinction from other diseases presenting with
pseudoepitheliomatous hyperplasia listed below.
Differential diagnosis (Pseudoepitheliomatous hyperplasia)
Chronic venous ulceration
Infections (including deep fungal infections, botryomycosis, atypical mycobacteria, verrucous tuberculosis)
Hypertrophic lichen planus
Halogenodermas (iododerma and bromoderma)
Superficial granulomatous pyoderma (a superficial variant of pyoderma gangrenosum)
Basal cell carcinoma
Granular cell tumour
CD30 + lymphoproliferative disorders (CD30+ Anaplastic Large Cell Lymphoma/ Lymphomatoid papulosis)
- Guitart J, Gordon K. Keratoacanthomas and lymphomatoid papulosis. Am J Dermatopathol 1998; 20: 430-433.
- Courville, P, Wechsler J, Thomine E, Vergier B, Fonck Y, Souteyrand P, Beylot-Barry M, Bagot M, Joly P. Pseudoepitheliomatous hyperplasia in cutaneous T- cell lymphoma. A clinical, histopathological and immunohistochemical study with particular interest in epithelial growth factor expression. The French Study Group on Cutaneous Lymphoma. Br J Dermatol 1999; 140: 421-426.
- Scarisbrick JJ, Calonje E, Orchard G, Child FJ, Russell-Jones R. Pseudocarcinomatous change in lymphomatoid papulosis and primary cutaneous CD30+ lymphoma: a clinicopathologic and immunohistochemical study of 6 patients. J Am Acad Dermatol 2001; 44: 239-247.
- Tronnier M, Merz H. Anaplastic large cell lymphoma and keratoacanthoma. Hautarzt 200; 55: 182-185.