Daryll Klein R.

Joaquin

Case Report
Squamous cell carcinoma in situ (Bowens disease)

Identifying Data
LG, an outspoken 72-year-old female, married, Filipino, residing in Quezon City.

Source and Reliability. Patient is remarkably reliable. She responds well and appropriately to questions asked.

Chief Complaint: Wart

History of Present Illness: One year prior to consult, patient noticed a 0.5 cm raised verrucous slow growing nodule at
the left thigh. This was associated with itchiness of 6/10 and pain of 5/10. Patient denied of any trauma, bleeding,
ulceration, or any other associated signs and symptoms.
During the interim, patient reported of progression and growth of the skin lesion. Patient also reported of
frequently scratching it. She however denied of any medications taken, ointments applied, or consults done during this
time.
Because of persistence and enlargement of the skin lesion, patient then decided to seek consult in our institution.
She was initially assessed as a case of seborrheic keratosis, rule out BCC, and with this, a skin punch biopsy was done to
confirm diagnosis.

Past Medical History

Family History
Mother has DM. With family history of hypertension for both sides. No family history of skin diseases.

Personal and Social History

Physical Examination

Solitary, 2.5 cm, well defined greyish brown hyperkeratotic verrucous plaque on top of a red plaque, on left
anterior thigh.
Histopathologic findings

The stratum corneum is alternatingly hyperkeratotic with parakeratosis and hyperkeratotic and basket weaved.
The epidermis is acanthotic with multiple dyskeratotic cells and large atypical keratinocytes.
Pleomorphism and hyperchromatism are noted. There is also crowding of epidermal cells.

Salient Features
Subjective Objective
72 year old female Solitary, 2.5 cm, well defined greyish brown hyperkeratotic
One-year history of enlarging, non healing skin verrucous plaque on top of a red plaque, on left anterior
lesion associated with itch and pain thigh.
alternatingly hyperkeratotic stratum with parakeratosis and
No history of trauma, bleeding or ulceration
basket weaved, as well as acanthtoic epidermis with multiple
Non smoker
dyskeratotic cells and large atypical keratinocytes, and
No previous history of skin disease
pleomorphism and hyperchromatism.

Differential Diagnoses
Seborrhoeic keratosis Highly considered as this is one of the most common skin disorders among elderly patients,
that tends to appear as 'stuck on' with a waxy or scaly appearance with varying degrees of pigmentation. However,
biopsy will only show proliferation of keratinocytes without atypia, often with pseudohorn cysts; hence this was ruled
out.
Basal cell carcinoma also highly considered as this is the most common skin malignancy. This usually appears as
pearly papules or plaques with rolled borders, telangiectasias, and ulceration when tumors become larger. However,
biopsy result tend to show tumor nests with basaloid differentiation with large nuclei and scant cytoplasm, and
significant keratinocyte atypia are also not found; hence this skin condition was also ruled out.
Squamous cell carcinoma highly considered also as this skin condition may also appear as exophytic, fungating,
verrucous nodules or plaques on skin. Histopathologic findings will usually reveal larger cells, with prominent nucleoli,
as well as foci of keratinization and formation of squamous whorls, which were seen in the patients skin lesion, hence
SCC, particularly Bowens disease, is highly considered.

Impression
Squamous cell carcinoma in situ, Bowens disease
Assessment
Squamous cell carcinoma is considered a malignant tumor of the skin that arises from the proliferation of atypical,
transformed keratinocytes in the skin that have undergone uncontrolled proliferation due to mutations and malignant
transformation of the cells. It is the second most common non-melanoma skin cancer worldwide (after basal cell cancer).
SCCs are most frequently observed in photoexposed skin, often in those >40 years of age. Also, SCC is the most common
skin cancer in patients with darker skin types, such as the patient.
Incidence also varies dramatically depending on cumulative sun exposure, and geographic latitude. In addition to
solar UV exposure, other factors are known to increase the risk of SCC, such as ionizing radiation, burns, previous
psoralen and UV-A light therapy, hereditary skin conditions, environmental toxins such as arsenic and tar, human
papillomavirus, and some immunocompromised states.
SCC ranges from in situ tumors, often called Bowen's disease, to invasive tumors and metastatic disease. In this
particular case, Bowens disease is actually a growth of cancerous cells that is confined only to the outer layer of the skin.
It is not a serious condition; however it can still progress into invasive squamous cell carcinoma if not managed
appropriately, which would already involve the deeper layers of the skin and may later on spread or metastasize. The rate
of transformation of Bowens in to invasive squamous cell carcinoma (SCC) is approximately 3%; although the
transformation rate is relatively low, immediate assessment and management are still warranted for such cases.

Diagnostic Approach
Presumptive diagnosis of Bowen disease is suspected based upon clinical findings, a detailed patient history and
a thorough clinical evaluation; however, skin biopsy confirms the diagnosis.
Initially, a thorough skin examination should be performed, including dermoscopy. Good lighting and possibly
handheld lenses may also be used. Patients with SCC of the skin often present with multiple actinic keratoses, which may
present as skin-colored, yellowish, or erythematous, ill-defined, irregularly shaped, small, scaly macules or plaques
localized to sun-exposed areas of the body. Any changes in shape or size, increased redness, induration, inflammation, or
bleeding of any such lesion should prompt investigation of a potential squamous cell carcinoma.
And to confirm the diagnosis of SCC, a biopsy must be performed. A punch biopsy is preferable to a curette
biopsy, as the full thickness of the epidermis and dermis can be viewed to establish whether there is any invasive disease
amounting to a cutaneous SCC.
Histological analysis of skin specimens routinely uses hematoxylin and eosin. The histological appearance
depends on the type of SCC but usually shows keratinocyte atypia. In Bowens disease, histopathology would usually
display full-thickness atypia that is confined to the epidermis, with an intact basement membrane. The involvement of the
entire thickness of the epidermis follows, and there is an absent granular layer, as well as parakeratosis.

Treatment Approach
The methods used to treat SCC in situ vary depending on tumor size and location, patient history, and
practitioner. Treatment can be surgical, locally destructive, or pharmacological.
Local destruction with liquid nitrogen or cryotherapy is commonly applied. This often results in a delayed
formation of a vesicle or bulla. In patients with darker skins, cryotherapy may cause hypopigmentation in the long term.
Electrodessication and curettage is another common method but carries the risk of depigmentation and scarring.
The dermatologist curettes the clinically apparent tumor, then coagulates the wound bed with electric current to dryness.
The eschar is curetted twice more with subsequent electrodessication.
Photodynamic therapy, whereby a topical photosensitizer, such as 5-aminolevulinic acid (ALA) or
methylaminolevulinic acid (MAL), induces protoporphyrin accumulation that results in cell death with exposure to visible
light, is now widely used and compares well with other methods. Studies have shown that the efficacy of photodynamic
therapy is similar to the cure rate of other traditional therapies, such as cryotherapy and electrodessication and curettage,
with superior cosmetic outcomes. The photochemical reaction causes death of actively dividing cells, which may result in
peeling, crusting, or blistering.
Conventional surgery is used for non-cosmetically sensitive locations and those <2 cm in diameter. Tumors <2
cm in diameter, not extending into subcutaneous fat, require at least a 4-mm margin. Mohs surgery, on the other hand, is
usually used for tumors on cosmetically sensitive areas such as the face, tumors >2 cm in diameter, and all recurrent
tumors. Tumors >2 cm in diameter that invade subcutaneous fat or involve high-risk locations such as the face require a
minimum of 6-mm margins. Of note, Mohs surgery provides the highest cure rate for SCC, at >97% for primary tumors. In
addition, it allows for optimal tissue sparing, as only the additional areas that carry tumors are removed.
Topical chemotherapy with fluorouracil (field therapy) targets abnormal cells by providing high local
concentrations of this chemotherapeutic agent without adverse systemic effects. The advantage of this approach is that
numerous lesions in an affected area are treated. Responsive lesions will become erosive within a few days to weeks
depending on the concentration of medication and frequency of application. Another option is topical imiquimod cream,
which was originally approved for treatment of genital warts.
Radiotherapy is another option for treatment of Bowen's disease, particularly those cases that are deemed
unresectable or in patients who are poor surgical candidates. A high rate of tumor control, with minimal morbidity and
preservation of normal tissues, has been demonstrated in most literatures.
A review of treatments for SCC in situ showed that when comparisons were made between surgical excision,
curettage, electrodesiccation, cryotherapy, 5-fluorouracil, imiquimod, radiation, photodynamic therapy, and lasers, no
single treatment was superior; hence, the specific situation of each individual patient must be taken into account in
determining management.

Prevention
Sunscreens with UV-A and UV-B spectrum coverage or sunblocks should be advised for secondary prevention.
Similarly, physical sun protection with clothing and hats, and sun avoidance should be emphasized. Emerging evidence
suggests that celecoxib may be an effective chemopreventive agent at decreasing the incidence of non-melanoma skin
cancer in patients with numerous actinic keratoses. Systemic retinoids have also been used as intervention for preventing
SCCs.

Prognosis
The risk of progression of Bowens disease to invasive squamous cell carcinoma ranges from 3-5%; whereas, the
3-year cumulative risk of a subsequent SCC after an index SCC is 18%. Lesions <2 cm in diameter have less than half the
local recurrence rate after excision (7%) compared with lesions >2 cm (17%), and less than one third of the rate of
metastasis. Overall prognosis depends on the depth of tumor invasion, histological pattern, and immunological status of
the patient.
References

Anna, Z., John, K., Maria, T., George, K., Ivelina, B., Ioanna, K., ... & Vassilis, K. (2012). The potential role of radiation
therapy in Bowen's disease: a review of the current literature. Reviews on recent clinical trials, 7(1), 42-46.
Barr, R. J. (1991). Classification of cutaneous squamous cell carcinoma. Journal of cutaneous pathology, 18(4), 225-226.
BathHextall, F. J., Matin, R. N., Wilkinson, D., & LeonardiBee, J. (2013). Interventions for cutaneous Bowen's disease.
The Cochrane Library.
Cassarino, D. S., DeRienzo, D. P., & Barr, R. J. (2006). Cutaneous squamous cell carcinoma: a comprehensive
clinicopathologic classification. Journal of cutaneous pathology, 33(4), 261-279.
Elmets, C. A., Viner, J. L., Pentland, A. P., Cantrell, W., Lin, H. Y., Bailey, H., ... & Richmond, E. (2010). Chemoprevention
of nonmelanoma skin cancer with celecoxib: a randomized, double-blind, placebo-controlled trial. Journal of the
National Cancer Institute, 102(24), 1835-1844.
Farasat, S., Siegrid, S. Y., Neel, V. A., Nehal, K. S., Lardaro, T., Mihm, M. C., ... & Sharfman, W. H. (2011). A new
American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma: creation and
rationale for inclusion of tumor (T) characteristics. Journal of the American Academy of Dermatology, 64(6),
1051-1059.
Farmer, K. C., & Naylor, M. F. (1996). Sun exposure, sunscreens, and skin cancer prevention: a year-round concern. The
Annals of pharmacotherapy, 30(6), 662-673.
Gordon, L. G., Scuffham, P. A., van der Pols, J. C., McBride, P., Williams, G. M., & Green, A. C. (2009). Regular
sunscreen use is a cost-effective approach to skin cancer prevention in subtropical settings. Journal of
Investigative Dermatology, 129(12), 2766-2771.
Morton, C. A., Brown, S. B., Collins, S., Ibbotson, S., Jenkinson, H., Kurwa, H., ... & Stringer, M. (2002). Guidelines for
topical photodynamic therapy: report of a workshop of the British Photodermatology Group. British Journal of
Dermatology, 146(4), 552-567.
Motley, R., Kersey, P., & Lawrence, C. (2003). Multiprofessional guidelines for the management of the patient with primary
cutaneous squamous cell carcinoma. British journal of plastic surgery, 56(2), 85-91.
Schmults, C. D., Karia, P. S., Carter, J. B., Han, J., & Qureshi, A. A. (2013). Factors predictive of recurrence and death
from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. JAMA dermatology, 149(5),
541-547.
Shimizu, I., Cruz, A., Chang, K. H., & Dufresne, R. G. (2011). Treatment of squamous cell carcinoma in situ: a review.
Dermatologic Surgery, 37(10), 1394-1411.