Clinical Diagnosis Versus Histological Diagnosis by Punch Biopsy to Determine the Subtype of Basal Cell Carcinoma
- Basal cell carcinoma throughout the world:
Skin cancer is the most common form of cancer, with basal cell carcinoma (BCC) being the
most frequent form of all skin cancers, and the incidence is still rising without future
signs of a plateau. Because there is no national registry for BCC in the Netherlands,
incidence rates are derived from the only register centre in the southern part of our
country. From a recent study we know that approximately 26.625 new patients with BCCs
occurred in 2006 in the Netherlands. The average number of BCC per patient is 1.65,
resulting in 44.000 new BCCs in that year. With an increase of approximately 10% per year
the estimated incidence rate at 2011 will be around 70.800 in the Netherlands. Three
important histopathologic subtypes of BCC can be distinguished, namely superficial, nodular
and aggressive. In the past, nodular basal cell carcinoma (nBCC) was the most common
histopathologic subtype, but superficial basal cell carcinoma (sBCC) and aggressive basal
cell carcinoma (aBCC) are the subtypes with the fastest growing incidences. Nowadays, the
distribution of histopathologic subtypes of BCC is 40.6% nodular, 30.7% superficial and
28.7% aggressive. The shift from nodular BCCs to other subtypes needs accurate detection of
the correct subtype, as treatment per subtype is different. The sharp raising incidence of
10% annually makes BCC an even bigger health problem in the near future.
- Diagnosis of BCC:
BCC is diagnosed with a 3 mm punch biopsy (PB) of the suspected skin lesion. Based on the
most aggressive histopathologic subtype seen in this biopsy, an appropriate treatment is
chosen. Three subtypes are relevant for a suitable treatment choice: superficial, nodular
and aggressive. The last one includes all BCCs with aggressive growth, such as
infiltrative/morpheaform BCC, micronodular BCC, and BCC with squamous differentiation.
Unfortunately, 31-33% of histopathologic subtypes seen on punch biopsies of primary and
recurrent BCCs do not correspond with the subtype seen in the subsequent surgical excision
(SE)/ Mohs micrographic surgery (MMS). The consequence is overtreatment and undertreatment.
- Guidelines on the treatment of basal cell carcinoma:
The national advisory board of Dutch dermatologists and plastic surgeons has published
multidisciplinary guidelines on the treatment of BCCs in 2007. In these guidelines the
different treatment options for all sort of BCCs are discussed and conclusions are drawn for
each treatment option. Recommended treatments for all BCCs regardless of the
histopathological subtype is SE. Both sBCC and nBCC have to be excised with 3 mm margin
while aggressive subtypes need a 5 mm margin. BCCs in the H-zone will be excised with MMS.
Photodynamic therapy (PDT), Imiquimod and 5-fluorouracil (5-FU) are also options for sBCC on
low-risk sites because of better cosmetic results.Recent studies show overall estimated
treatment success at 5-year follow-up of 65% for PDT and 78-80% for Imiquimod. These
percentages are far lower than the 99% overall estimated treatment success of SE in sBCC.
There is no literature on treatment effect of 5-FU at long term follow-up. Only two studies
report 86-87% complete response rate to different 5-FU treatment regimens after 6-12 weeks.
- Treatment of basal cell carcinoma at the Maastricht University Medical Center (MUMC):
In the past, BCC has been a disease of the elderly patient but as a consequence of
recreational sun exposure and tanning beds, more young patients develop a skin cancer as
well. Therefore, cosmetic results play a more important role when choosing a suitable
treatment. Therefore in today's dermatologic practice at the MUMC patients with a sBCC can
be treated non-invasively with PDT, Imiquimod, 5-FU or with SE/MMS. These non-invasive
treatments show good cosmetic results but higher recurrence rates than SE. Any
non-responding or recurrent sBCC has to be retreated with SE/MMS.
- Undertreatment and overtreatment:
Preliminary data from our own study show that in case of a discrepancy between
histopathologic BCC subtype in the PB and excision, 58% of patients are overtreated and 42%
undertreated. Half of the overtreated patients will have a histological nBCC or aBCC on PB,
but only superficial in the SE/MMS. This could be partly due to the fact that the most
suspected part has already been biopsied and is not present in surgical excision anymore.
Overtreatment consists of unnecessary tissue loss because of too wide SE margins. In
addition, large excisions might lead to more complications like scarring, infection,
continued or subsequent bleeding and dehiscent wounds. Undertreated patients have to be
re-treated again in case of positive resection margins with SE, resulting in extra stress
for patients, time and health care costs.
- Clinical diagnosis:
Histological diagnosis of BCC subtype by PB might not be the perfect procedure because of
the 30% mismatch with the subtype seen in the SE/MMS. A potential better way to determine
the BCC subtype might be the clinical diagnosis. To our knowledge, there is no literature
about the observed agreement of the clinical diagnosis to determine the most aggressive
histological subtype of BCC. We want to confirm the hypothesis that the clinical diagnosis
is as good as or even better than the histological diagnosis by PB to determine the most
aggressive BCC subtype. Confirmation of this hypothesis will result in clinical diagnosis
instead of punch biopsies, more patients receiving early and correct treatment, saving time
and health care costs. The conclusions from the proposed study can serve as a basis for
updating guidelines for the diagnosis of BCC.
Time Perspective: Prospective
Diagnostic value of clinical diagnosis
The current proposal aims at establishing the observed agreement of the clinical diagnosis to and histological diagnosis to detect the most aggressive BCC subtype of the entire tumour.
Within 24 hours after the patient presents at the outpatient department of dermatology
Nicole WJ Kelleners-Smeets, MD, PhD
Maastricht University Medical Center, Maastricht, the Netherlands
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
MEC 112041 (35344.068.11)