basal cell carcinoma workup_ approach considerations, skin biopsy, cytology

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1/6/2016 Basal Cell Carcinoma Workup: Approach Considerations, Skin Biopsy, Cytology

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Basal Cell Carcinoma Workup

Author: Robert S Bader, MD; Chief Editor: William D James, M D more...

Updated: Sep 15, 2015

Approach Considerations

Given that basal cell carcinoma rarely metastasizes, laboratory and imaging studies are not commonly clinicallyindicated in patients presenting with localized lesions. Imaging studies may be necessary when involvement of

deeper structures, such as bone, is clinically suspected. In such cases, CT scans or radiography can be used.

Skin Biopsy

A skin biopsy is often required to confirm t he diagnosis and determine t he histologic subtype of basal cell carcinoma(BCC). Most often, a shave biopsy is all that is required. Nevertheless, in the case of a pigmented lesion where

here may be difficulty distinguishing between pigmented BCC and melanoma, an excisional or punch biopsy maybe indicated; this is to ensure that the depth of the lesion can be determined if it proves to be a malignant

melanoma.

In most cases, a superficial biopsy specimen that contains dermis is all that is required to confirm the diagnosis of BCC, although it is possible to miss the tumor. For example, an ulcerated BCC may reepithelialize with normal

epidermis while tumor is still present at a deeper level. Part or all of the BCC may be sampled, but avoid goingbeyond the clinical margins if the biopsy is only for diagnostic purposes.

Punch biopsy is an easy method to obtain a thick specimen, but is rarely required. The most suspicious area of alesion may be sampled, or multiple biopsy samples may be taken if the tumor is large or has a varied appearance indifferent areas. Avoid punch biopsy if curettage is planned for final treatment.

Occasionally, suspected tumors may require more than a single biopsy to make the diagnosis; therefore, with a highclinical index of suspicion, a second biopsy may be needed to obtain a pathological diagnosis of BCC.

Cytology

To accurately and definitively diagnose BCC of the eyelid, histological confirmation is required and is most

commonly obtained through excisional (shave or punch) biopsy, which provides more information regarding thehistological subtype of BCC. Cytology does provide a rapid alternative that may yield and even help confirm a

diagnosis during the initial visit, however.

The accuracy of this technique has been reported to be good, but its sensitivity in diagnosing BCC of the eyelid isunknown. It is not considered to be sufficiently sensitive in planning surgical management.

A study by Barton et al showed that for patients who underwent cytology followed by excisional biopsy, cytology had

a sensitivity of 92% in diagnosing BCC with a predictive accuracy of 75%. [57] These values were compared to asecond group of patients who had incisional biopsy and histological examination followed by excision withhistological confirmation. The second group showed a sensitivity of 100% in diagnosing BCC with a predictive

accuracy of 96%.

Histologic Findings

Several histologic types of BCC exist. Distinctions are important because clinical detection of tumor margins is more

difficult with certain histologic types.[58] Usually, BCCs are well differentiated and cells appear histologically similar o basal cells of the epidermis.

Tumor cells of nodular BCC, sometimes called basalioma cells, typically have large, hyperchromatic, oval nuclei and

little cytoplasm. Cells appear uniform, and if present, mitotic figures are usually few. The nuclei resemble that of thebasal cells of the epidermis, although they have a larger nuclear-to-cytoplasmic ratio and lack intercellular bridges. A

mitotic figure is very rarely observed. Nodular tumor aggregates may be of varying sizes, but tumor cells tend toalign more densely in a palisade pattern at the periphery of these nests (see the image below).

Nodular basal cell carcinoma. Nodular aggregates of basalioma cells are present in the dermis and exhibit peripheral palisading andretraction artifact. Melanin is also present within the tumor and in the surrounding stroma, as seen in pigmented basal cellcarcinoma.

Cleft formation, known as retraction artifact, commonly occurs between BCC nests and stroma because of shrinkage of mucin during tissue fixation and staining. Some lobules may have areas of pseudoglandular change,

and this is the predominant change in adenoid BCC. In other instances, large tumor lobules may degeneratecentrally, forming pseudocystic spaces filled with mucinous debris. These changes are seen in the nodulocystic

variant of BCC.





Early lesions usually have some connection to the overlying epidermis, but such contiguity may be difficult to

appreciate in more advanced lesions. Increased mucin is often present in the surrounding dermal stroma.

A histopathologic examination of paraffin-embedded sections of BCC usually reveals solid cellular strands,collections of cells with dark-staining nuclei and scant cytoplasm.

The peripheral cell mass is in a palisade arrangement that resembles the basal layer of the epidermis, sometimeswith pseudocystic aspects, and with a variable number of mitoses.

The connective tissue stroma surrounding the tumor islands is arranged in parallel bundles and often shows youngfibroblasts immediately adjacent to the tumor. The specific histologic pattern of each type of BCC varies in terms of desmoplastic reaction of the morpheaform type and in the stromal islands separated by basal cells strands of the

fibroepithelial type. Artificial retraction of the stroma from the tumor islands is frequently observed histologically. Additionally, the stroma i s oft en m ucinous. Cells f rom recurrent B CC often show squamous aspects.

Histologically, BCC is divided into 2 categories: undifferentiated and differentiated. When there is little or nodifferentiation, it is referred to as solid BCC and includes pigmented BCC, superficial BCC, sclerosing BCC, and

infiltrative BCC (a histologic subtype).

Differentiated BCC often has slight differentiation toward cutaneous appendages, including hair (keratotic BCC),sebaceous glands (BCC with sebaceous differentiation), or tubular glands (adenoid BCC). Noduloulcerative (nodular)

BCC is usually differentiated. See the images below.

Histologic pattern of a well-differentiated basal cell carcinoma (original magnification X140). (Image courtesy of Prof Pantaleo Bufo,University of Foggia, Italy)







hen the presence of a dense inflammatory infiltrate obscures the histologic margins of BCC,immunohistochemical stains for cytokeratins can help to identify tumor cells. These stains can be used with fixed or frozen tissue. Such staining with frozen tissue can take as little as 19 minutes, making it practical for use with Mohs

micrographic surgery or with standard excision with frozen section margin control.[59]

Nodular basal cell carcinoma

Nodular or noduloulcerative basal cell carcinoma, the most common type, generally consists of large, round or oval

umor islands within the dermis, often with an epidermal attachment. The solid (nodular) type accounts for approximately 70% of all cases. Artificial retraction of the tumor islands from the surrounding stroma is commonlyseen. Ulcerations may be seen in large tumors.

Micronodular basal cell carcinoma

Another aggressive variant, micronodular B CC, appears as small, nodular aggregates of basaloid cells. See theimage below.

Micronodular basal cell carcinoma often has an absence of retraction artifact. The characteristic histology is small size anduniformity of the tumor nodules. (Image courtesy of Shang I Brian Jiang, MD)

Retraction artifact tends to be less pronounced than in the nodular form of BCC, and subclinical involvement is

often significant. Micronodular basal cell carcinoma is similar to the noduloulcerative type, although the tumor

islands are small (often < 15 cells in diameter).

Pigmented basal cell carcinoma

In pigmented basal cell carcinoma (BCC), benign melanocytes in and around the tumor produce large amounts of

melanin. These melanocytes contain many melanin granules in their cytoplasm and dendrites. Superficial BCC (seehe image below) appears as buds of basaloid cells attached to the undersurface of the epidermis. Nests of various

sizes are often seen in the upper dermis. The tumor cell aggregates typically show peripheral palisading.





Histology of superficial basal cell carcinoma. Nests of basaloid cells are seen budding from the undersurface of the epidermis.(Image courtesy of Michael L Ramsey, MD)

Adenoid basal cell carcinoma

The adenoid type consists of strands of basaloid cells in a reticulate pattern, frequently with prominent stromal

mucin. It may occur with the solid type.

Morpheaform (sclerosing) basal cell carcinoma

The more aggressive morpheaform BCCs have growth patterns resulting in strands of cells rather than round nests,within a fibrous stroma. They constitute approximately 5% of BCCs. Morpheaform BCC arises as thin strands of umor cells (often only 1 cell in thickness) that are embedded in a dense fibrous stroma. The morpheaform basal

cell carcinomas exhibit islands of tumor extending into the tissue and may exhibit perineural invasion in 3% of patients. This finding helps classify these 2 histotypes as the most aggressive, with the highest rates of recurrence

and positive margins after excision.

Infiltrative basal cell carcinoma

This type of BCC accounts for 10% of BCCs. Tumor cells have growth patterns resulting in strands of cellsinfiltrating between collagen bundles rather than round nests.

The strands of infiltrating BCC tend to be somewhat thicker than those seen in morpheaform BCC, and they have aspiky, irregular appearance (see the image below).

Infiltrative basal cell carcinoma. Tumor cells are arranged in narrow strands, and mucin-rich stroma is often present. (Imagecourtesy of Shang I Brian Jiang, MD)

Infiltrating BCC usually does not exhibit the scarlike stroma seen in morpheaform BCC. Peripheral palisading and

retraction are less pronounced in morpheaform and infiltrating BCC than in less aggressive forms of the tumor, andsubclinical involvement is often extensive.

Cystic basal cell carcinoma

Cystic basal cell carcinoma consists of large, round or oval tumor islands within the dermis with mucin present in the

center of the island. This space is caused by central tumor cell degeneration.

Superficial basal cell carcinoma

The (multifocal) superficial type (see the image below) is characterized by numerous small nests of tumor cellsusually attached to the undersurface of the epidermis by a broad base. Approximately 10-15% of all BCCs are of his type. This is the most common pattern seen in BCCs of the shoulder.





Histology of superficial basal cell carcinoma. Nests of basaloid cells are seen budding from the undersurface of the epidermis.(Image courtesy of Michael L Ramsey, MD)

Keratotic basal cell carcinoma

The keratotic type resembles the solid type and its nests of basaloid cells with peripheral palisading. The island

centers display keratinization and squamous differentiation. See the image below.

Keratotic basal cell carcinoma. Rare type characterized by keratocysts. (Image courtesy of Shang I Brian Jiang, MD)

Infundibulocystic basal cell carcinoma

The infundibulocystic type is rare and is usually found on the face. It resembles the keratotic type. Nests arearranged in an anastomosing pattern and lack stroma. Many small, infundibular cyst-like structures with keratinous

material are present. Melanin is sometimes present.

Metatypical basal cell carcinoma

Metatypical BCC is rare. In this type, nests and strands of cells mature into larger and paler cells, and peripheralpalisading, if any, is less developed than in other types. Prominent stroma, prominent mitotic activity, and many

apoptotic cells may be present. This form may be best diagnosed when one evaluates a BCC with features betweenhose of a nodular BCC and squamous cell carcinoma. These tumors are often aggressive, with an increased

endency for lymphatic and perineural spread.

Basosquamous carcinoma

The basosquamous type is controversial. It has been defined as a basal cell carcinoma (BCC) with differentiationowards squamous cell carcinoma (SCC). It is made up of basaloid cells that are a larger, paler, and rounder thanhose of a solid BCC. It also consists of squamoid cells and intermediate cells. Some consider the diagnosis of this

ype most appropriate when one evaluates a tumor with contiguous areas of BCC and SCC. This type is considered

o have metastatic potential and is considered an aggressive skin cancer (see the image below).

Basosquamous basal cell carcinoma. Foci of neoplastic cells with squamous differentiation are present. (Image courtesy of Shang IBrian Jiang, MD)

Fibroepithelioma of Pinkus

The fibroepithelioma type consists of thin, anastomosing strands of basaloid cells in a prominent stroma.





According to some studies, the so-called f ibroepithelioma of Pinkus, considered to be a premalignant skin condition,

must be considered as a fenestrated variant of basal cell carcinoma. [60, 61, 62]

Ultrasonography

The use of ultrasonography is controversial. High-frequency (20 MHz) and ultra-high-frequency (40-100 MHz)

ultrasound systems have been used; their accuracy in delineating malignant lesions from benign lesions remainsinadequate, however, with a success rate of approximately 20%. Furthermore, the claims of reliable tumor sizingand depth of invasion are promising but still passionately debated.

Laser Doppler

As an adjunct tool, laser Doppler may assist ophthalmologists in distinguishing between benign and m alignant

adnexal skin lesions and in establishing the tumor margin.

It is reported that cutaneous perfusion to the eyelids is statistically significantly higher than other regions of the body

(eg, forearm). Furthermore, the mean perfusion in pretarsal skin has been shown to be 50% greater than that inpreseptal skin. In histologically documented basal cell carcinoma of the eyelid, cutaneous perfusion was significantly

greater. [63]

Staging

Basal cell carcinoma rarely metastasizes and is usually not staged, unless the cancer is very large and is suspectedof spreading to other parts of the body. BCC staging may be similar to the staging of squamous cell carcinoma,

which is according to the following scheme:

Stage 0: Cancer involves only the epidermis and has not spread to the dermis

Stage I: Cancer is not large (ie, < 2 cm) and has not spread to the lymph nodes or other organsStage II: Cancer is large (ie, >2 cm) but has not spread to lymph nodes or other organs

Stage III: Cancer has spread to tissues beneath the skin (eg, muscle, bone, cartilage), and/or to regionallymph nodes but not to other organs.

Stage IV: Cancer can be any size and has spread to other organs

High-risk tumors

High-risk BCCs include the following:

Recurrent or incompletely excised BCCPrimary BCC with clinically indistinct borders

Lesions in high-risk (the H, or mask) areas, mainly the embryonic fusion planes (eg, eyelids, nose, ear,nasolabial folds, upper lip, vermillion border, columella, periorbital region, temples, preauricular and

postauricular areas, and scalp)Lesions that develop in cosmetically and functionally important areas (eg, face, genitals, anal and perianal

regions, hands and feet, and the nail unit areas)Tumors with aggressive clinical behavior (ie, growing rapidly or >2 cm)Tumors with aggressive histologic subtype, including sclerosing (morpheaform), basosquamous (metatypical

or keratinizing), perineural, periappendageal, or perivascular invasion, infiltrating, adenoidal, or multicentricTumors that develop in sites with previous radiation therapy

Tumors that develop in immunosuppressed patients

Treatment & Management

Contributor Information and Disclosures

Author Robert S Bader, MD Dermatologist, Section of Dermatology, Department of Medicine, Broward Health - North

Robert S Bader, MD is a member of the following medical societies: American A cademy of Dermatology, Florida

Medical Association, American S ociety for Dermatologic Surgery, American S ociety for MOHS Surgery

Disclosure: Nothing to disclose.

Coauthor(s)Andrew Scott Kennedy, MD Physician-in-Chief, Radiation Oncology

Andrew S cott Kennedy, M D is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Society f or Radiation Oncology, Radiological Society of North

America, Americas Hepato-Pancreato-Biliary Association, American S ociety of Clinical Oncology


Luigi Santacroce, MD Assistant Professor, Medical School, State University at Bari, Italy


Laura Diomede University of Bari School of Medicine, Italy


Specialty Editor BoardFrancisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center Collegeof Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director,

Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American A cademy of Dermatology,

Society for Investigative Dermatology


Acknowledgements

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Health Network; Professor, Temple University School of Medicine

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Cooperative Oncology Group, and European Society for Medical Oncology

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Michael Giono Barakat California Surgical Institute


Daniel Berg, MD, FRCP(C) Professor of Dermatology, Director of Dermatologic Surgery, University of

Washington School of Medicine

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School of Medicine

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Robert A Copeland Jr, MD Chair, Professor, Department of Ophthalmology, Howard University College of

Medicine

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Mark T Duffy, MD, PhD Consulting Staff, Division of Oculoplastic, Orbito-facial, Lacrimal and ReconstructiveSurgery, Green Bay Eye Clinic, BayCare Clinic; Medical Director, Advanced Cosmetic Solutions, A BayCare

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and Society for Neuroscience

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and Ear; Senior Lecturer of Neurosciences:Anatomy and Physiology, Nevada State College

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Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

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Shang I Brian Jiang, MD Associate Clinical Professor of Medicine and Dermatology, Director, Dermatologic andMohs Micrographic Surgery, Program Director, UCSD Dermatologic and Mohs Surgery Fellowship, University of

California School of Medicine, San Diego

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American College of Mohs S urgery, American S ociety for Dermatologic Surgery, and Association of Professors

of Dermatology

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School of Medicine

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