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) and Erasmus Medical Center (Erasmus MC) Rotterdam.
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 and Erasmus MC 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 sensitivity and specificity of the
clinical diagnosis to determine the subtype of BCC seen in the SE/MMS specimen.
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 BCC subtype
compared to the gold standard of SE/MMS. 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.

To establish the diagnostic value of clinical diagnosis to predict the
histological BCC subtype and compare this by the diagnostic accuracy of PB to
determine the subtype of BCC in the subsequent SE/MMS specimen.

Clinical, prospective, multi-centre study

There is no burden for patients with nBCC or aBCC. The will be treated
according to regular care.

The burden for patients with a sBCC is minimal. The visits and procedures that
will take place mostly don't differ from regular care like physical
examination, photography and punch biopsy. In regular care, patients can choose
between surgical treatment with low recurrence rates or non-invasive treatment
with better cosmetic results. Patient who participate in the study have no
choice and will all be treated with SE or MMS.

The SE will approximately take 30 minutes and the MMS 2-8 hours, depending on
the number of excisionrounds. After injection with a local anaesthetic this is
a painless procedure. The injection can give a burning sensation. Risks of
surgical excision might be scarring, continued or subsequent bleeding,
infection or dehiscent wounds.