111: Basal Cell Carcinoma and Basal Cell Nevus Syndrome Flashcards
What are the primary risk factors for developing Basal Cell Carcinoma (BCC)?
The primary risk factors for BCC include:
- UV radiation exposure
- Light hair and eye color
- Northern European ancestry
- Inability to tan
What are the common clinical features of Basal Cell Carcinoma (BCC)?
Common clinical features of BCC include:
- Translucency
- Ulceration
- Telangiectasias
- Presence of a rolled border
What is the most common subtype of Basal Cell Carcinoma (BCC) and its characteristics?
The most common subtype of BCC is Nodular BCC. Characteristics include:
- Occurs on sun-exposed areas of the head and neck
- Appears as a translucent papule or nodule
- Usually has telangiectasias and often a rolled border
- Larger lesions with central necrosis are referred to as rodent ulcers.
What is the significance of the Sonic Hedgehog (SHH) signaling pathway in Basal Cell Carcinoma (BCC)?
The Sonic Hedgehog (SHH) signaling pathway is pivotal in the pathogenesis of BCC. Key points include:
- Malignant activation of this pathway is a common abnormality in BCCs.
- Common mutations that activate this pathway include loss of PTCH1 or Suppressor of Fused (SUFU) and activation of Smoothened (SMO).
- Approximately 90% of sporadic BCCs have identifiable mutations in at least one allele of PTCH1.
What are the preferred biopsy methods for diagnosing Basal Cell Carcinoma (BCC)?
The preferred biopsy methods for diagnosing BCC are:
- Shave biopsy
- Punch biopsy
How does the clinical presentation of Basal Cell Carcinoma typically manifest on the skin?
BCC typically presents as:
- Translucent papule or nodule
- Ulceration
- Telangiectasias
- Presence of a rolled border
What histological features are commonly observed in Basal Cell Carcinoma?
Common histological features of BCC include:
- Large nuclei with relatively little cytoplasm
- Absence of mitotic features
- Slit-like retraction of stroma forming tumor islands
- Peritumoral lacunae that assist in histopathologic diagnosis.
What are the top three most common subtypes of Basal Cell Carcinoma, and where do they typically occur?
The top three most common subtypes of BCC, in order of frequency, are:
1. Nodular BCC - typically occurs on the head and neck.
2. Superficial BCC - commonly found on the trunk.
3. Morpheaform BCC - also primarily located on the head and neck.
What are the histological features of Pigmented BCC?
- Approximately 75% of BCCs contain melanocytes, but only 25% contain large amounts of melanin.
- Melanocytes are interspersed between tumor cells and contain numerous melanin granules in their cytoplasm and dendrites.
- Tumor cells may contain little melanin, but numerous melanophages populate the stroma surrounding the tumor.
What is the appearance and differential diagnosis of Superficial BCC?
- Appearance: Most commonly presents as a well-demarcated erythematous patch on the trunk, resembling an isolated patch of eczema that does not respond to treatment.
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Differential Diagnoses:
- Squamous Cell Carcinoma (SCC)
- Lichenoid keratosis
- Nummular dermatitis
What are the histological characteristics of Morpheaform (Sclerosing, Infiltrative) BCC?
- Appearance: May have an ivory-white appearance and resemble a scar or morphea.
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Histology:
- Strands of tumor cells embedded within a dense fibrous stroma.
- Tumor cells are closely packed, sometimes only 1-2 cells thick.
- Strands of tumor extend deeply into the dermis, often larger than the clinical appearance.
What is the gold standard treatment for Basal Cell Carcinoma (BCC)?
- The gold standard for treatment of BCC is the removal of tumor with clear margins.
- Most effective treatments include:
- Surgery
- Radiotherapy
What are the recurrence rates for different treatment modalities for primary BCC?
Treatment Modality | Recurrence Rate |
|—————————————|—————–|
| Mohs Micrographic Surgery (MMS) | 1% |
| Standard Excision | 10% |
| Curettage and Desiccation | 7.7% |
| Radiation Therapy (XRT) | 8.7% |
| Cryotherapy | 7.5% |
What are the preferred treatments for recurrent BCC?
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MMS is preferred for:
- Recurrent BCC
- Any BCC that occurs at a site where tissue conservation is desired.
What is the significance of Mohs Micrographic Surgery (MMS) in the treatment of BCC, particularly for recurrent cases?
Mohs Micrographic Surgery (MMS) is significant in the treatment of BCC because:
- It offers superior histologic analysis of tumor margins, allowing for maximal conservation of tissue compared to standard excision.
- The recurrence rate for primary BCCs treated with MMS is only 1%, which is lower than other modalities.
How does the treatment approach differ for recurrent BCC compared to primary BCC?
The treatment approach for recurrent BCC differs from primary BCC in the following ways:
- Recurrent BCC is more likely to be relatively resistant to further treatments, necessitating more aggressive management.
A patient presents with a translucent papule on the head with telangiectasias and a rolled border. What is the most likely subtype of BCC, and what is the recommended treatment?
The most likely subtype is nodular BCC. The recommended treatment is Mohs micrographic surgery (MMS) for its superior histologic analysis and tissue conservation.
A patient with a history of BCC presents with a scar-like lesion on the face. What subtype of BCC should be suspected, and what is the preferred treatment?
The suspected subtype is morpheaform BCC, an aggressive variant. The preferred treatment is Mohs micrographic surgery (MMS).
A patient has a well-demarcated erythematous patch on the trunk that resembles eczema but does not respond to treatment. What is the likely diagnosis, and what histological features support it?
The likely diagnosis is superficial BCC. Histological features include buds of malignant cells extending into the dermis, peripheral palisading cells, and minimal dermal invasion.
A patient with a history of sun exposure presents with a hyperpigmented, translucent papule. What subtype of BCC is this, and what are the differential diagnoses?
This is pigmented BCC. Differential diagnoses include nodular melanoma and seborrheic keratosis.
A patient presents with a pink papule on the lower back. What subtype of BCC is this, and what is the differential diagnosis?
This is fibroepithelioma of Pinkus. The differential diagnosis includes acrochordon (skin tag).
A patient with a history of BCC presents with a lesion showing both basal cell and squamous cell differentiation. What subtype of BCC is this, and what histological features support it?
This is basosquamous BCC. Histological features include infiltrating jagged tongues of tumor cells and areas showing squamous intercellular bridge formation and cytoplasmic keratinization.
A patient with a history of BCC presents with a lesion on the nasofacial junction. What treatment is preferred, and why?
Mohs micrographic surgery is preferred because it is particularly useful for high-risk anatomic sites like the nasofacial junction.
A patient with a history of BCC presents with a lesion on the trunk. What subtype is most likely, and what are the histological features?
The most likely subtype is superficial BCC. Histological features include buds of malignant cells extending into the dermis and minimal dermal invasion.
A patient with a history of BCC presents with a lesion that resembles a scar. What subtype should be suspected, and what is the histological hallmark?
The suspected subtype is morpheaform BCC. The histological hallmark is strands of tumor cells embedded within a dense fibrous stroma.
A patient with a history of BCC presents with a lesion that has both basal cell and squamous cell features. What is the subtype, and what is the clinical significance?
The subtype is basosquamous BCC. It is clinically significant due to its aggressive nature and potential for local destruction.
A patient with a history of BCC presents with a lesion on the retroauricular sulcus. What treatment is preferred, and why?
Mohs micrographic surgery is preferred because it is effective for high-risk anatomic sites like the retroauricular sulcus.
A patient with a history of BCC presents with a lesion on the face. What is the gold standard treatment, and why?
The gold standard treatment is Mohs micrographic surgery because it offers superior histologic analysis and tissue conservation.
A patient with a history of BCC presents with a lesion that has recurred after standard excision. What is the next best treatment option?
The next best treatment option is Mohs micrographic surgery, which has a lower recurrence rate for recurrent BCCs.
A patient with a history of BCC presents with a lesion that has recurred after radiation therapy. What is the next best treatment option?
The next best treatment option is Mohs micrographic surgery, which has a lower recurrence rate compared to radiation therapy.
A patient with a history of BCC presents with a lesion on the face that is poorly delineated. What is the preferred treatment, and why?
The preferred treatment is Mohs micrographic surgery because it is effective for poorly delineated lesions.
A patient with a history of BCC presents with a lesion that has recurred after curettage and desiccation (C&D). What is the next best treatment option?
The next best treatment option is Mohs micrographic surgery, which has a lower recurrence rate for recurrent BCCs.
A patient with a history of BCC presents with a lesion on the face that is larger than 2 cm. What is the preferred treatment, and why?
The preferred treatment is Mohs micrographic surgery because it offers superior margin control for large lesions.
What are the advantages and disadvantages of surgery as a treatment for Basal Cell Carcinoma (BCC)?
Advantages:
- Offers histologic evaluation compared to non-excisional techniques.
- Surgery is the standard of choice for BCC.
Disadvantages:
- Cure rates are inferior to Mohs Micrographic Surgery (MMS) for primary morpheaform BCC, recurrent BCCs, and tumors located in high-risk anatomic areas.
What factors influence the cure rate of curettage and desiccation in treating BCC?
The cure rate of curettage and desiccation is influenced by:
- Operator experience:
- Private practitioners: 94.3% cure rate
- Residents: 81.2% cure rate
- Lesion size:
- Lesions <1.0 cm: 98.8% cure rate
- Lesions 1.0 to 2.0 cm: 95.5% cure rate
- Lesions >2.0 cm: 84% cure rate
What is the cure rate for private practitioners treating BCC?
94.3% cure rate
What is the cure rate for residents treating BCC?
81.2% cure rate
What is the cure rate for lesions less than 1.0 cm in size?
98.8% cure rate
What is the cure rate for lesions between 1.0 to 2.0 cm in size?
95.5% cure rate
What is the cure rate for lesions greater than 2.0 cm in size?
84% cure rate
What are the potential complications associated with cryosurgery for BCC?
Hypertrophic scarring and post-inflammatory pigmentary changes.
What should raise suspicion for recurrent BCC after cryosurgery?
Any recent change in a cryosurgery scar after normal healing.
What is the mechanism of action of Imiquimod 5% cream in treating superficial BCC?
Acts as a Toll-like receptor 7 agonist, inducing interferon-α, tumor necrosis factor-α, and other cytokines.
What are the response rates for superficial BCC treated with Photodynamic Therapy (PDT)?
85% to 93% at 3 months, comparable to cryosurgery at 60 months (75% vs 74%).
What are the recurrence rates for BCC after PDT?
Ranges from 0% to 31%.
What are the advantages of Radiation Therapy (XRT) in treating BCC?
Minimal patient discomfort and avoidance of invasive procedures.
What is perineural invasion (PNI) in the context of BCC?
Defined as the observation of malignant cells in the perineural space of nerves, identified in fewer than 0.2% of cases.
How should perineural invasion (PNI) be managed?
Efforts should be made to clear the tumor, preferably by Mohs Micrographic Surgery (MMS).
What are the advantages of surgery as a treatment for BCC?
Offers histologic evaluation and is the standard of choice for BCC treatment.
What are the limitations of surgery for BCC?
Cure rates are inferior to Mohs Micrographic Surgery (MMS) for certain types of BCC.
How does the curettage and desiccation technique vary based on lesion size?
Cure rates decrease as the size of the primary lesion increases.
What are the potential complications associated with cryosurgery for BCC treatment?
Hypertrophic scarring and post-inflammatory pigmentary changes.
What is the mechanism of action of Imiquimod 5% cream?
Acts as a Toll-like receptor 7 agonist, inducing interferon-α and other cytokines.
What are the response rates for superficial BCC treated with PDT?
85% to 93% at 3 months, with long-term cure rates around 75%.
What are the advantages of using Radiation Therapy (XRT) for BCC treatment?
Minimal patient discomfort and avoidance of invasive procedures.
What is the prognosis for metastatic BCC?
Poor, with a mean survival time of 8-10 months without treatment.
What is Basal Cell Nevus Syndrome (BCNS) also known as?
Nevoid basal cell carcinoma syndrome and Gorlin Syndrome.
What genetic mutation is associated with Basal Cell Nevus Syndrome?
Inactivating mutation in the PTCH1 gene.
What is the prevalence of Basal Cell Nevus Syndrome?
Estimated at 1 in 31,000 to 1 in 60,000 persons.
What are the three most characteristic abnormalities associated with Basal Cell Nevus Syndrome?
Tumors (medulloblastomas or BCCs), pits of palms and soles, and odontogenic cysts of the jaw.
What is the response rate for Vismodegib in treating metastatic BCC?
33.3% response rate.
What are the aggressive histologic characteristics identified as risk factors for BCC?
Morpheaform features, squamous metaplasia, and perineural invasion (PNI).
What factors are associated with the risk of metastasis in basal cell carcinoma (BCC)?
Size of the tumor (>7.5 cm) and a long delay in seeking treatment.
What treatment options are available for metastatic basal cell carcinoma (BCC)?
Platinum-based chemotherapy, combination of cisplatin and paclitaxel, and carboplatin and paclitaxel.
What are the FDA-approved Hedgehog inhibitors for locally advanced or metastatic BCC?
Vismodegib and sonidegib.
What is the significance of mutations in PTCH1 and SMO in basal cell carcinomas (BCCs)?
Mutations in PTCH1 are common in BCNS tumors; mutations in SMO can lead to resistance to PTCH1 inhibition.
What role does PTCH1 play in the hedgehog signaling pathway?
PTCH1 inhibits the hedgehog signaling pathway by inhibiting the function of SMO.
What are the three most characteristic features of Basal Cell Nevus Syndrome (BCNS)?
Tumors (medulloblastomas or basal cell carcinomas), pits of the palms and soles, and keratocystic odontogenic tumors of the jaw.
What are palmoplantar pits and their significance in BCNS diagnosis?
Small defects in the stratum corneum that may aid in diagnosing BCNS.
What skeletal abnormalities are associated with Basal Cell Nevus Syndrome?
Overall larger body size, long limbs with a marfanoid appearance, and large head circumference.
What is the significance of mutations in PTCH1 and SMO in basal cell carcinomas (BCCs)?
Mutations in PTCH1 are the most common in BCNS tumors and are often consistent with UV light-induced mutations. Mutations in SMO can render it resistant to PTCH1 inhibition, leading to upregulation of hedgehog target gene expression, which is crucial for BCC formation.
What role does PTCH1 play in the hedgehog signaling pathway and how does its dysfunction contribute to tumor formation?
PTCH1 inhibits the hedgehog signaling pathway by blocking the function of the SMO receptor. When hedgehog binds to PTCH1, this inhibition is relieved, activating the pathway. Loss of PTCH1 function leads to unregulated SMO activity, resulting in tumor formation.
How do the characteristics of BCCs in patients with BCNS differ from sporadic cases?
BCCs in BCNS patients cannot be distinguished from sporadic cases based on histology. However, they are characterized by their appearance in larger numbers at an early age, often resembling nevocytic nevi or having a translucent, papulonodular appearance.
What are the clinical implications of palmoplantar pits in the diagnosis of BCNS?
Palmoplantar pits are small defects in the stratum corneum that may appear early in life and can aid in the diagnosis of BCNS. Their presence, along with other symptoms, can indicate the syndrome’s diagnosis.
What skeletal abnormalities are commonly associated with BCNS, and how might they present clinically?
Skeletal abnormalities in BCNS often manifest as overall larger body size compared to family members, long limbs with a marfanoid appearance, large head circumference, and frontal bossing.
What is the significance of odontogenic cysts in patients with BCNS, and how do they typically present?
Odontogenic cysts are often the first detectable abnormality in BCNS and may be asymptomatic, diagnosed only through radiographs. They can cause pain, swelling, and loss of teeth, particularly in the mandibular jaw.
A patient with multiple BCCs and a family history of similar lesions is suspected of having a genetic syndrome. What syndrome is likely, and what gene mutation is associated?
The likely syndrome is Basal Cell Nevus Syndrome (BCNS), associated with mutations in the PTCH1 gene.
A patient with BCNS presents with jaw cysts and palmoplantar pits. What is the pathogenesis of these findings?
Jaw cysts are due to inappropriate SHH induction of dental epithelium, and palmoplantar pits are thought to result from aborted attempts to generate hair follicles in the palms.
A patient with BCNS has a large head circumference and frontal bossing. What other skeletal abnormalities might be present?
Other skeletal abnormalities may include long limbs with a marfanoid appearance and abnormalities of the ribs, spine, and phalanges.
A patient with BCNS has multiple BCCs in sun-protected areas. What factors accelerate BCC formation in these patients?
Sunlight and ionizing radiation accelerate BCC formation in BCNS patients.
A patient with BCNS is undergoing genetic counseling. What is the inheritance pattern of the associated gene mutation, and what is the likelihood of transmission to offspring?
The inheritance pattern is autosomal dominant. There is a 50% likelihood of transmission to offspring.
What are the major complications associated with Basal Cell Nevus Syndrome (BCNS)?
Major complications include developmental delay, physical impairment in children, childhood tumors (such as medulloblastoma), and locally aggressive BCCs that rarely metastasize.
What are the recommended management strategies for patients with Basal Cell Nevus Syndrome (BCNS)?
The most important aspects of management include frequent examination of the skin for lesions, counseling about avoidance of sun exposure, and early treatment of small tumors.
What is the significance of genotyping in the context of Basal Cell Nevus Syndrome (BCNS)?
Genotyping is significant because it allows for prenatal diagnosis of BCNS, which is potentially achievable for interested families.
What are the non-surgical approaches recommended for the treatment of Basal Cell Carcinoma (BCC) in BCNS patients?
Non-surgical approaches include minimization of discomfort and scarring, topical treatments such as 5-FU, imiquimod, and PDT, and retinoids.
What are the potential side effects of oral vismodegib in the treatment of BCC?
Potential side effects of oral vismodegib (150mg/day) include muscle cramps, loss of taste, and hair loss.
What are the major complications associated with Basal Cell Nevus Syndrome (BCNS) during childhood or adolescence?
Major complications include developmental delay, physical impairment in children, childhood tumors (such as medulloblastoma), and locally aggressive BCCs.
How does the presence of jaw cysts relate to the diagnosis of Basal Cell Nevus Syndrome (BCNS)?
Jaw cysts often appear at the start of the 2nd decade of life and are considered a significant indicator in the evaluation for BCNS.
What is the significance of genotyping and identification of the PTCH1 gene in patients suspected of having Basal Cell Nevus Syndrome (BCNS)?
Genotyping and identification of the PTCH1 gene are crucial for confirming the diagnosis of BCNS, as mutations in this gene are associated with the syndrome.
What is the typical latency period between time of UV damage and clinical onset of BCC?
20 - 50 years
Why is BCC rare in individuals with dark skin?
Because of the inherent photoprotection of melanin and melanosomal dispersion.
What are the 4 risk factors for BCC formation?
- UVR 2. Light hair and eye color 3. Northern European ancestry 4. Inability to tan
What are the top 3 most common forms of BCC?
- Nodular 2. Superficial 3. Morpheaform
What type of treatment for BCC appears to have good cosmetic outcomes?
Photodynamic therapy (PDT)
What is the standard treatment of choice for BCC?
Surgical excision
What are the risk factors for BCC metastasis?
Morpheaform, squamous metaplasia, perineural invasion (PNI)
What is the FDA approved drug for metastatic BCC that may lead to tumor resistance?
Sonidegib
Fill in the blanks: ___ and ___ accelerated BCC formation in BCNS patients.
Sunlight and radiation
What is the first detectable abnormality in BCNS?
Jaw cysts
What is frequently the initial sign of BCNS?
Medulloblastoma
Which drug is the most effective in preventing formation of new BCCs in BCNS patients?
Vismodegib 150mg/day
What are the 3 most important aspects of management for BCNS?
- Frequent examination 2. Counseling about sun avoidance 3. Early treatment of small tumors
T/F: BCNS patients have multiple BCCs which are locally aggressive and have the potential to metastasize.
True
Fill in the blanks: Suspect BCNS in a patient with BCCs before age of ___, odontogenic keratocysts before age of ___, and with ___ or more palmar or plantar pits.
20, 15, 3
