121: Neoplasias and Hyperplasias of Muscular and Neural origin Flashcards
What are the three categories of benign neoplasms of the skin with smooth muscle differentiation?
The three categories are: 1. Piloleiomyomas (synonym: pilar leiomyoma) 2. Solitary leiomyoma (including dartic, vulvar, nipple, and areolar types) 3. Angioleiomyomas (deriving from smooth muscle tissue of vessel walls)
What is the typical presentation of piloleiomyomas?
Piloleiomyomas typically appear as multiple, firm, brown-red to pearly discrete papulonodules. In the nascent stage, they are more easily palpable than visible. They commonly occur on the face, back, and extensor sites of the extremities.
What genetic mutation is commonly associated with multiple cutaneous leiomyomas?
Most patients presenting with multiple cutaneous leiomyomas have a germline loss-of-function mutation in the fumarate hydratase (FH) gene, which may also act as a tumor suppressor gene.
What is Reed syndrome and its association with leiomyomas?
Reed syndrome, also known as multiple leiomyomatosis, is characterized by women developing early onset uterine leiomyomas along with multiple cutaneous leiomyomas. The cutaneous tumors typically occur in the late second or third decade of life prior to the diagnosis of uterine lesions.
What are the major criteria for diagnosing hereditary leiomyomatosis and renal cell carcinoma (HLRCC)?
The major criteria for diagnosing HLRCC include: 1. Multiple cutaneous leiomyomas with at least 1 biopsy proven/histologically confirmed. 2. Early-onset renal cell carcinoma of Type II papillary histology. 3. Positive germline FH-mutation test.
What are the three microanatomical origins of smooth muscle tumors?
Smooth muscle tumors can originate from: 1) arrector pili muscles, 2) smooth muscle of genital skin (e.g., scrotum, vulva, nipple, areolar region), and 3) walls of blood vessels.
What histological features are characteristic of smooth muscle lesions?
Smooth muscle lesions are characterized by spindled cells with abundant brightly eosinophilic cytoplasm and blunt-ended (cigar-shaped) nuclei.
What immunohistochemical markers are used to identify smooth muscle antigens?
Smooth muscle antigens can be identified using markers such as α-smooth muscle actin (α-SMA), muscle-specific actin, desmin, and H-caldesmon.
What are the three subtypes of superficial benign smooth muscle tumors?
The three subtypes are: 1) Piloleiomyomas (arising from arrector pili muscles), 2) Leiomyomas of genital sites and the nipple/areola, and 3) Angioleiomyomas (arising from vessel walls).
What is Reed syndrome, and what are its associated risks?
Reed syndrome, also known as multiple cutaneous and uterine leiomyomatosis, is associated with early-onset uterine leiomyomas and a risk of renal cell carcinoma (papillary Type II).
What are the clinical features of piloleiomyomas?
Piloleiomyomas typically appear as multiple, firm, brown-red to pearly discrete papulonodules, often on the face, back, and extensor sites of extremities.
What are the common symptoms associated with leiomyomas?
Common symptoms include: - Spontaneous or secondary pain, particularly with exposure to cold. - Genital leiomyomas are rare and usually small, seldom exceeding 2 cm in diameter. - Scrotal leiomyomas are firm nodules, typically larger (1 to 14 cm in diameter). - Vulval tumors typically arise in the labia majora, measuring 1 to 5 cm. - Angioleiomyomas are slowly enlarging nodules on the extremities, particularly the lower leg, more frequent in females, except for those in the oral cavity.
What histopathological features are characteristic of pilar leiomyoma?
Pilar leiomyoma is characterized by: - Dermal-based tumor with possible focal involvement of the superficial subcutis. - Ill-defined bland-appearing spindle cells with blunt-ended, cigar-shaped nuclei. - Eosinophilic cytoplasm arranged in interweaving fascicles. - Blending in an irregular fashion with surrounding dermal collagen and adjacent pilar muscle. - Absence of atypia or mitotic activity. - Strong expression of smooth muscle actin, desmin, muscle-specific actin, and h-caldesmon.
What is the clinical course and prognosis for cutaneous leiomyomas?
The clinical course and prognosis for cutaneous leiomyomas include: - Generally considered not to undergo malignant transformation. - Recurrence after complete excision is unusual. - The lifetime renal cancer risk for FH mutation carriers is estimated to be 15%.
What are the management options for leiomyomas?
Management options for leiomyomas include: 1. Simple excision 2. CO2 laser ablation 3. Cryotherapy 4. Electrosurgery (when surgical excision is not feasible) 5. Symptomatic treatment options: - Nitroglycerin - Nifedipine - Phenoxybenzamine - Gabapentin - Intralesional botulinum toxin - Topical analgesics
What is the epidemiology of leiomyosarcoma?
The epidemiology of leiomyosarcoma includes: - Accounts for 5% to 10% of soft tissue sarcomas. - Principally tumors of adults, but can occur in all age groups. - No gender predilection. - Atypical intradermal smooth muscle neoplasms affect middle-aged to elderly adults, with a male-to-female ratio of nearly 5:1.
What are the subgroups of superficial leiomyosarcomas?
Subgroups of superficial leiomyosarcomas include: - Dermal leiomyosarcomas, which derive from arrector pili muscles or smooth muscle at genital sites.
What are the histological features of pilar leiomyomas?
Pilar leiomyomas are dermal-based tumors with ill-defined spindle cells containing blunt-ended nuclei and eosinophilic cytoplasm, arranged in interweaving fascicles.
What is the differential diagnosis for pilar leiomyomas?
The differential diagnosis includes dermatofibromas, dermal melanocytic nevi, neurofibromas, schwannomas, angiolipomas, adnexal tumors, and metastases.
What are the management options for cutaneous leiomyomas?
Management options include simple excision, CO2 laser ablation, cryotherapy, electrosurgery, and symptomatic treatments like nitroglycerin, nifedipine, and gabapentin.
What are the clinical findings associated with leiomyosarcomas?
Leiomyosarcomas typically present as solitary lesions, which can include: - Deep-seated, firm nodules with occasional ulceration and hyperplasia of the epidermis. - Dermal tumors that are usually fixed to the epidermis. - Rarely exceed 3 cm in diameter. - Subcutaneous lesions may rapidly develop into larger, well-circumscribed tumor nodules. - Associated with hyperpigmentation and erythema of the involved skin. - Predilection for hair-bearing areas of lower extremities, scalp, and trunk. - More common in males and typically appear between the fifth and seventh decades of life.
What histopathological features are characteristic of leiomyosarcomas?
The histopathological features of leiomyosarcomas include: - Composed of intersecting fascicles of atypical spindle cells. - Low grade tumors are well differentiated. - Intermediate grade tumors show characteristic cytomorphology indicative of smooth muscle differentiation, with large, elongated fusiform cells and abundant eosinophilic cytoplasm. - High grade tumors are poorly differentiated, exhibiting marked nuclear pleomorphism and a high mitotic rate (>10 mitoses/10 HPF). - Dermal tumors are ill-defined, with tumor fascicles ramifying through surrounding collagen and pilar arrector muscle. - Subcutaneous tumors are more circumscribed due to the pseudocapsule generated by compression of adjacent collagenous tissue.
What is the differential diagnosis for leiomyosarcomas?
The differential diagnosis for leiomyosarcomas includes: - Clinical DDx: - Dermatofibroma - Dermatofibrosarcoma - Neurofibroma - Squamous cell carcinoma (SCC) - Atypical fibroxanthoma - Pleomorphic dermal sarcoma - Melanoma - Adnexal tumors - Cysts - Histologic DDx includes nonpleomorphic spindle cell tumors: - Cellular dermatofibroma: lacks well-defined tumor bundles and shows different immunohistochemical markers. - Cellular schwannoma: encapsulated neoplasm with spindle cells and S-100 protein expression. - Malignant peripheral nerve sheath tumor (MPNST): shows loss of specific markers. - Myopericytoma/myofibroma: typically shows a whorled arrangement of tumor cells with specific staining characteristics.
What are the subgroups of superficial leiomyosarcomas?
The subgroups include dermal leiomyosarcomas (arising from arrector pili muscles or genital smooth muscle) and subcutaneous leiomyosarcomas (arising from vascular smooth muscle).
What are the clinical features of dermal leiomyosarcomas?
Dermal leiomyosarcomas present as deep-seated, firm nodules, often fixed to the epidermis, and rarely exceed 3 cm in diameter.
What histological features differentiate low-grade, intermediate-grade, and high-grade leiomyosarcomas?
Low-grade tumors are well-differentiated, intermediate-grade tumors show moderate differentiation with eosinophilic cytoplasm, and high-grade tumors exhibit marked nuclear pleomorphism and high mitotic rates (>10 mitoses/10 HPF).
What are the distinguishing features of leiomyosarcomas that arise on the head and neck compared to pleomorphic spindle-cell neoplasms?
Leiomyosarcomas must be distinguished from pleomorphic spindle-cell neoplasms by the following features: - Spindle-cell (sarcomatoid) SCC: Focally positive for keratin, but desmin and h-caldesmon are not expressed. - Melanoma: Presence of atypical lentiginous melanocytic hyperplasia and/or a junctional tumor component, with expression of S-100 protein, HMB-45, MART-1, MITF, SOX10, and NGFR/p75(NTR). - Spindle-cell angiosarcoma: Characterized by multilayering, papillary structures, irregular anastomosing blood vessels, and immunophenotyping for ERG. - Atypical fibroxanthoma: Diagnosed in actinically damaged skin, often positive for CD10.
What is the clinical course and prognosis for most tumors associated with leiomyosarcomas?
The clinical course and prognosis for most tumors associated with leiomyosarcomas are as follows: - Favorable outcomes: Most tumors are small (<2 cm) and highly differentiated, often cured with timely wide surgical excision. - Recurrence rates: Incompletely excised tumors have a recurrence rate of 20% to 30%, with margin status being the only predictor of local recurrence. - Risk factors for metastasis: Include tumor size, degree of subcutaneous involvement, high histologic grade, and previous local recurrence.
What are the management strategies for smooth muscle hamartomas?
Management strategies for smooth muscle hamartomas include: 1. Wide surgical excision: At least 3-cm margins with careful histologic examination of surgical margins is the treatment of choice. 2. AISMN: Complete excision with negative margins due to substantial risk for local recurrence. 3. Mohs micrographic surgery: Used as an alternative treatment modality, with a reported recurrence rate of 14%.
What are the clinical findings associated with smooth muscle hamartomas?
Clinical findings associated with smooth muscle hamartomas include: - Appearance: Skin-colored or lightly pigmented patch or plaque measuring up to 10 cm in diameter. - Location: Predilection for the lumbar region of the trunk, buttocks, and proximal extremities. - Spectrum of presentations: - Solitary lesions - Agminated lesions - Michelin tire baby syndrome: Generalized variant with excess symmetrical skin folds, occasional hypertrichosis, and follicular dimpling. - Pseudo darier sign: Small papules may be detectable within the lesions and sensitive to transient piloerection following rubbing.
What are the risk factors for metastatic spread in leiomyosarcomas?
Risk factors include tumor size, degree of subcutaneous involvement, high histologic grade, and previous local recurrence.
What is the recommended treatment for superficial leiomyosarcomas?
Wide surgical excision with at least 3-cm margins is the treatment of choice. Mohs micrographic surgery is an alternative with a reported recurrence rate of 14%.
What are the clinical features of smooth muscle hamartomas?
Smooth muscle hamartomas present as skin-colored or lightly pigmented patches or plaques, often in the lumbar region, buttocks, or proximal extremities, and may display hyperpigmentation and hypertrichosis.
What are the histopathological features of smooth muscle fibers in leiomyomas?
- Well-defined and thickened smooth muscle fibers - Haphazardly oriented in reticular dermis - Some fibers surround or are attached to hair follicles - Thin retraction spaces separate muscle bundles from adjacent collagen - Constituent cells express α-SMA and desmin
What are the differential diagnoses for smooth muscle hamartomas?
- Becker nevus - Congenital Melanocytic nevus - Neurofibroma - Connective tissue nevus - Solitary mastocytoma - Leiomyomas: appear as papulonodules, with smooth muscle fibers arranged in interweaving fascicles blending with adjacent dermal collagen fibers.
What is the clinical course and prognosis for smooth muscle hamartomas?
- Do not undergo malignant transformation. - Associated with congenital anomalies in conditions like Michelin tire baby syndrome. - Management may be indicated for cosmetic purposes, typically involving surgical excision.
What are the main categories of rhabdomyomas and their epidemiological significance?
- Rhabdomyomas account for no more than 2% of all striated muscle neoplasms, much less common than rhabdomyosarcomas. - Two main categories: - Cardiac - Extracardiac (Adult type, Fetal type, Genital type) - Fetal-type and adult-type rhabdomyomas predominantly affect men (male-to-female ratio is 3:1).
What are the histopathological characteristics of adult and fetal types of rhabdomyoma?
Type | Characteristics |
|——|—————-|
| Adult Type | Composed of variously sized,
What are striated muscle neoplasms?
Striated muscle neoplasms are much less common than rhabdomyosarcomas.
What are the two main categories of rhabdomyomas?
The two main categories are cardiac rhabdomyomas and extracardiac rhabdomyomas (adult type, fetal type, and genital type).
What is the male-to-female ratio for fetal-type and adult-type rhabdomyomas?
The male-to-female ratio is 3:1.
What are the histopathological characteristics of adult-type rhabdomyomas?
Adult-type rhabdomyomas are composed of variously sized, deeply eosinophilic polygonal cells with small, peripherally placed nuclei and occasional intracellular vacuoles.
What are the histopathological characteristics of fetal-type rhabdomyomas?
Fetal-type rhabdomyomas resemble fetal skeletal muscle and include classic/myxoid and intermediate/cellular types.
What does the classic/myxoid fetal-type rhabdomyoma consist of?
The classic/myxoid type is composed of primitive oval or spindle-shaped cells and a richly myxoid stroma.
What does the intermediate/cellular fetal-type rhabdomyoma consist of?
The intermediate/cellular type consists of intersecting bundles of differentiated eosinophilic myofibrils containing cross-striations, with fewer or absent spindle-shaped cells.
What is the histological appearance of smooth muscle hamartomas?
Smooth muscle hamartomas consist of well-defined, thickened smooth muscle fibers in the reticular dermis, often attached to hair follicles, with thin retraction spaces separating muscle bundles from adjacent collagen.
What is the differential diagnosis for smooth muscle hamartomas?
The differential diagnosis includes Becker nevus, congenital melanocytic nevus, neurofibroma, connective tissue nevus, solitary mastocytoma, and leiomyomas.
What is the clinical presentation of fetal-type rhabdomyomas?
Fetal-type rhabdomyomas are rare tumors that occur in the head and neck region in both children and adults, resembling fetal skeletal muscle histologically.
What is the most common type of rhabdomyosarcoma?
Embryonal rhabdomyosarcoma (ERMS) is the most common type, accounting for 60% of cases.
What genetic factor is associated with embryonal rhabdomyosarcoma?
It is associated with an 11p15.5 loss of heterozygosity.
What are the clinical findings associated with rhabdomyosarcoma?
Rhabdomyosarcoma can occur at various anatomic sites, with the head and neck region being the most common. It may present as a rapidly growing mass that can ulcerate and is often palpable.
What is the estimated risk of local recurrence for adult-type rhabdomyoma following incomplete excision?
Adult-type rhabdomyoma carries an estimated 42% risk of local recurrence following incomplete excision.
What is the significance of rhabdomyoblasts in the diagnosis of rhabdomyosarcoma?
Rhabdomyoblasts are essential for the diagnosis of rhabdomyosarcoma, characterized by large round, spindle-shaped, or elongated cells with eosinophilic granular cytoplasm and cross-striations.
What are the three histologic subsets of rhabdomyosarcomas?
The three subsets are embryonal rhabdomyosarcoma (ERMS), alveolar rhabdomyosarcoma (ARMS), and anaplastic/undifferentiated/pleomorphic rhabdomyosarcoma.
What genetic translocations are associated with alveolar rhabdomyosarcoma (ARMS)?
ARMS is associated with t(2;13)(q35;q14) translocation (PAX3-FOXO1A) and t(1;13)(p36;q14) translocation (PAX7-FOXO1A).
What are the histological features of embryonal rhabdomyosarcoma (ERMS)?
ERMS consists of small, round or spindle-shaped cells with alternating cellular and myxoid zones.
What is the clinical presentation of primary cutaneous rhabdomyosarcoma?
Primary cutaneous rhabdomyosarcoma presents as a rapidly growing mass that may ulcerate, often resulting from the expansion of an underlying soft-tissue lesion.
What are the immunohistochemical markers with the highest diagnostic value in pediatric small blue round-cell tumors?
The immunohistochemical markers with the highest diagnostic value are Myogenin and MyoD1.
What are the clinical features of Rhabdomyomatous mesenchymal hamartoma?
The clinical features include a small dome-shaped papule or polypoid pedunculated lesion in the midline region of the skin, most frequently on the chin.
What is the differential diagnosis for Rhabdomyomatous mesenchymal hamartoma?
The differential diagnosis includes nevus lipomatosus superficialis and fibrous hamartoma of infancy.
What are the goals of treatment for neuromuscular hamartoma?
The goals include amelioration of symptoms and maintaining nerve integrity.
What are the cell types associated with peripheral nerve sheath tumors?
The cell types include Schwann cells, which give rise to neuromas, schwannomas, and neurofibromas.
What immunohistochemical markers are diagnostic for rhabdomyosarcoma?
Myogenin and MyoD1 are the most diagnostic markers for rhabdomyosarcoma.
What is the prognosis for botryoid rhabdomyosarcoma?
Botryoid rhabdomyosarcoma has a superior prognosis, with 5-year survival rates of 90% to 95%.
What is the management approach for rhabdomyosarcoma?
Management involves a multidisciplinary approach, including biopsy or surgical removal, chemotherapy, and possibly radiotherapy.
What is rhabdomyomatous mesenchymal hamartoma?
Rhabdomyomatous mesenchymal hamartoma is a rare congenital lesion composed of a mixture of mature adipose, skeletal muscle tissue, adnexal structures, and sometimes blood vessels and nerves.
What is the histological appearance of neuromuscular hamartomas?
Neuromuscular hamartomas consist of bundles of perpendicularly oriented skeletal muscles intermingled with multiple small nerve fascicles.
What are perineurial cells and how do they differ from Schwann cells?
Perineurial cells are specific fibroblasts that give rise to perineuriomas and differ from Schwann cells by lacking a basement membrane.
What types of cells are predominantly located in the endoneurium?
The non-specific mesenchymal cells predominantly located in the endoneurium include fibroblasts and mast cells.
What are the three main entities of cutaneous peripheral nerve sheath tumors?
The three main entities are neuromas, schwannomas (neurilemomas), and neurofibromas.
What are the cell types of peripheral nerves that give rise to tumors?
Peripheral nerve tumors arise from Schwann cells, perineurial cells, and non-specific mesenchymal cells.
What immunohistochemical markers differentiate Schwann cells from perineurial cells?
Schwann cells express S-100 protein but not EMA, while perineurial cells express EMA, GLUT1, and claudin-1 but not S-100 protein.
What is the clinical significance of neurofibromas in neurofibromatosis type 1 (NF-1)?
Neurofibromas in NF-1 have a risk of malignant transformation into malignant peripheral nerve sheath tumors.
What are the common clinical presentations of Pilar Leiomyoma?
Common presentations include a firm papule, nodulo-solitario, and usually painless.
What is the typical age range for patients with Angioleiomyoma?
The typical age range is adults from 10 to 50 years of age.
What are the histopathological features of Rhabdomyosarcoma?
Histopathological features include rhabdomyoblasts, multinucleated giant cells, and atypical mitotic figures.
What is the management approach for Smooth Muscle Hamartoma?
The management approach is surgical excision.
What associated syndromes are linked with Rhabdomyosarcoma?
Associated syndromes include HLRCC (hereditary leiomyomatosis and renal cell cancer).
What is the typical size range for a Rhabdomyosarcoma tumor?
The typical size range is 0.5 to 15 cm.
What are the genetic features associated with Smooth Muscle Hamartoma?
Genetic features include PITCH (patch hedgehog) and fusions for fetal rhabdomyosarcoma.
What is the clinical presentation of Rhabdomyosarcoma in adults?
The clinical presentation is a rapidly growing, subcutaneous or superficial mass.
What are the key architectural features used to differentiate between types of cutaneous muscular proliferation?
Key architectural features include thick-walled vessels in angioleiomyoma and the presence of smooth muscle differentiation in rhabdomyoblasts.
What are the characteristics of cutaneous neural proliferations?
Characteristics include S-100+ spindle-cell proliferation and nodular growth patterns.
What are the common clinical symptoms associated with Traumatic Neuroma?
Symptoms include itching, prickling, and pain in 10% to 30% of cases.
What is the typical management approach for Neurofibroma?
The typical management approach is surgical excision.
What histopathological features are associated with Schwannoma?
Histopathological features include well-circumscribed tumor and multiple closely packed Schwann cells.
What is the incidence of Nerve Sheath Myxoma and its common age group?
Nerve Sheath Myxoma is very rare, with an average incidence age of 36 years.
What genetic mutations are associated with Granular Cell Tumor?
Granular Cell Tumor is associated with mutations in NF1 (1p13.2) and deletions of the NF2 gene.
What is the epidemiology of traumatic (amputation) neuroma?
The range of symptomatic traumatic neuromas is between 10% to 30%, and they can present at any age.
What are the clinical findings associated with traumatic neuroma?
Clinical findings include firm, oval, flesh-colored, occasionally painful papules or nodules that occur in the subcutis or deeper soft tissues, typically at sites of previous trauma, in amputation stumps, and in scars.
What is the histopathology of traumatic neuroma?
Histopathology shows a haphazard proliferation of nerve fascicles, including axons with myelin sheaths, Schwann cells, and fibroblasts embedded in a collagenous stroma. There may be concentric condensations of fibrous tissue around individual fascicles, and perineurial cells expressing EMA surround each fascicle.
What is the management approach for traumatic neuroma?
Management includes:
- Attempting to reappose disconnected nerve ends to enable regeneration.
- Providing temporary pain relief with a nerve block.
- Surgical excision of the lesion and repositioning of the proximal nerve stump into a scar-free area.
What is rudimentary polydactyly and its clinical findings?
Rudimentary polydactyly refers to a nodular tumor that rarely appears on the ulnar surface of the proximal fifth finger, containing a disordered proliferation of nerve fascicles. Clinical findings include a raised nodule on the ulnar border of the proximal fifth finger.
What is the histopathology of rudimentary polydactyly?
Histopathology reveals multiple bundles of nerve fibers embedded in connective tissue in the upper dermis and dermal papillae, with numerous Meissner corpuscles present.
What is the epidemiology of palisated encapsulated neuroma?
Palisated encapsulated neuromas appear during adulthood, mostly in the third to fifth decade, and affect both males and females equally. They account for approximately 25% of all cutaneous nerve sheath tumors.
What are the clinical findings associated with palisated encapsulated neuroma?
Clinical findings include small, asymptomatic, flesh-colored, firm papules or nodules that may arise at any location, with approximately 90% of cases diagnosed in the area of the face, primarily around the nose and lips.
What is the histopathology of palisated encapsulated neuroma?
Histopathology shows nodular or polypoid, well-circumscribed, dermal-based tumors surrounded by a thin perineurial connective tissue capsule. It features multinodular and plexiform growth patterns, with solid proliferations composed of multiple closely packed fascicles of Schwann cells and abundant axons.
What are the differential diagnoses for palisated encapsulated neuroma?
Differential diagnoses include dermal melanocytic nevus, basal cell carcinoma, adnexal tumor, and neurofibroma. Histopathological differentials include schwannoma and neurofibroma.
A patient presents with a painful, firm, flesh-colored nodule at the site of a previous trauma. Histopathology reveals a haphazard proliferation of nerve fascicles embedded in a collagenous stroma. What is the most likely diagnosis and management?
The most likely diagnosis is a traumatic (amputation) neuroma. Management includes surgical excision of the lesion and repositioning of the proximal nerve stump into a scar-free area.
A newborn presents with a raised nodule on the ulnar border of the proximal fifth finger. Histopathology shows multiple bundles of nerve fibers embedded in connective tissue. What is the diagnosis and the recommended management?
The diagnosis is rudimentary polydactyly. Recommended management is primary surgical excision with high transection and retraction of the accessory digital nerve to prevent postoperative neuroma formation.
A 35-year-old patient presents with a small, asymptomatic, flesh-colored nodule on the face near the nose. Histopathology reveals a well-circumscribed dermal-based tumor with multinodular growth patterns. What is the diagnosis and its histological markers?
The diagnosis is palisaded encapsulated neuroma (PEN). Histological markers include EMA positivity in the perineurial cell-rich capsule and S-100 protein positivity in spindle-shaped tumor cells.
What is the prevalence of Mucosal Neuromas and Multiple Endocrine Neoplasia Syndrome Type 2B?
The prevalence of Mucosal Neuromas and Multiple Endocrine Neoplasia Syndrome Type 2B is 1 in 600,000 patients to 1 in 4,000,000 patients.
What are the clinical findings associated with MEN2B?
Clinical findings associated with MEN2B include:
- Early development of medullary thyroid carcinoma in all affected individuals.
- Pheochromocytomas in approximately 50% of individuals.
- Multiple mucosal neuromas, which appear by age 2 as pink, pedunculated, painless papules on mucosal surfaces.
- Other cutaneous signs include café au-lait spots, facial lentigines, and hyperpigmentation of the hands and feet.
What is the management goal for individuals with MEN2B?
The management goals for individuals with MEN2B include:
- Identification of individuals with germline gain-of-function mutations of the RET gene associated with MEN2B.
- Reduction of morbidity and mortality in high-risk individuals via:
- Prophylactic thyroidectomy or screening for medullary thyroid cancer.
- Catecholamine urine testing, serum calcium, and parathyroid hormone levels.
- Genetic analysis of the RET gene for patients with clinical evidence of MEN2B and at-risk family members.
What are the characteristics of Schwannomas?
Schwannomas are benign nerve sheath neoplasms characterized by:
- Derived from the proliferation of Schwann cells within nerve sheaths.
- Surrounded by a true capsule consisting of epineurium.
- Approximately 60% harbor inactivating mutations of the NF2 gene located at 22q12.2.
- Sites of predilection include peripheral nerves at flexor sites, cranial and cervical nerves, and spinal roots.
What is the typical age range for the occurrence of Schwannomas?
Schwannomas typically occur mostly between the ages of 20 and 60 years.
A 2-year-old child presents with pink, pedunculated, painless papules on the mucosal surfaces of the lips and tongue. Genetic analysis reveals a RET protooncogene mutation. What is the diagnosis and the associated syndrome?
The diagnosis is mucosal neuromas, associated with Multiple Endocrine Neoplasia Syndrome Type 2B (MEN2B).
What are the clinical findings associated with schwannomas?
- Soft, slowly growing, skin-colored to yellowish dermal or subcutaneous nodules
- Usually solitary and measure 1-4 cm in diameter
- Small tumors are asymptomatic
- Larger lesions may cause pain, tenderness, and neurologic symptoms
- Plexiform schwannomas represent approximately 15% of all cutaneous schwannomas and may be clinically recognizable as intradermal multinodular masses.
What is Schwannomatosis and its genetic implications?
- Schwannomatosis is a genetic disorder characterized by multiple cranial, spinal, and peripheral schwannomas without vestibular schwannomas or other signs of NF-1 or NF-2.
- Incidence ranges from 1 in 140,000 to 1.7 million.
- Occurs mostly sporadically, may involve autosomal dominant transmission.
- Somatic mutations of the NF2 gene are frequently detected in schwannomas of schwannomatosis patients.
What are the histopathological features of schwannomas?
- Well-circumscribed, encapsulated, nodular true nerve sheath proliferations, usually limited to the subcutis.
- Tumor parenchyma is exclusively composed of Schwann cells.
- Fibrous capsule consists of epineurium and residual nerve fibers.
- Hallmark pattern includes two alternating tissue areas: Antoni A (high cellularity) and Antoni B (low cellularity).
What differentiates plexiform schwannomas from other types of schwannomas?
- Plexiform schwannomas are characterized by a plexiform pattern that is often associated with multinodularity.
- They have a propensity for the skin and may present in the dermis and/or subcutis, unlike other types which may not exhibit this pattern.
What is the clinical course and prognosis for schwannomas?
- Malignant transformation is rare in classic schwannomas but occurs in over 10% of melanotic schwannomas.
- 50% of the psammomatous variant is associated with the Carney syndrome.
What is the management approach for schwannomas?
The treatment of choice for schwannomas is simple excision.
What is the epidemiology of neurofibromas?
- Neurofibromas typically arise in individuals between the ages of 20 and 30 years.
- Plexiform neurofibromas are pathognomonic of NF-1.
What is the etiology and pathogenesis of neurofibromas?
- Neurofibromas can occur sporadically or in the context of NF-1, which is inherited as an autosomal dominant trait with a high rate of penetrance.
- The NF1 gene product, neurofibromin 1, regulates activation of the Ras intracellular signaling pathway in Schwann cells.
A patient presents with a soft, slowly growing, skin-colored nodule on the flexor site of the upper extremity. Histopathology reveals alternating Antoni A and Antoni B areas. What is the diagnosis and its hallmark histological feature?
The diagnosis is schwannoma. The hallmark histological feature is the presence of Verocay bodies in Antoni A areas.
A patient presents with a multinodular mass in the dermis and subcutis. Histopathology reveals Schwann cells with melanosomes. What is the diagnosis and its associated syndrome?
The diagnosis is melanotic schwannoma. It is associated with the Carney complex in 50% of cases.
What are the three subtypes of neurofibromas based on architectural growth patterns?
- Localized neurofibromas: Most common type (90% of all tumors), presents as slowly growing, skin-colored, soft or rubbery papules or nodules, and shows a (+) buttonhole sign.
- Diffuse neurofibromas: Mainly affect children and young adults, frequently located in subcutaneous tissues of the head and neck, 90% are solitary lesions not associated with NF-1, and typically cause a plaque-like elevation of the skin.
- Plexiform neurofibromas: Involve a long nerve segment and its branches, forming bag-like or pedunculated masses, associated with massive soft-tissue overgrowth, usually occur in early childhood, and are pathognomonic of NF-1.
What is the clinical significance of plexiform neurofibromas in relation to NF-1?
Plexiform neurofibromas have a recognized potential for malignant transformation and are considered a precursor for Malignant Peripheral Nerve Sheath Tumors (MPNST) in NF-1 patients.
What are the key histopathological features of nerve sheath myxoma?
Nerve sheath myxoma is characterized by:
- Nonencapsulated tumors forming distinct multilobulated or multinodular masses with abundant myxoid matrix and a peripheral fibrous border.
- Composed of small epithelioid Schwann cells arranged in cords, nests, or syncytial-like aggregates.
- Tumor cells strongly express S-100 protein, glial fibrillary acidic protein, neuron-specific enolase, and CD57.
What are the two forms of perineurioma and their characteristics?
- Intraneural perineurioma: Presents as a fusiform swelling of a major nerve, often with signs of mononeuropathy.
- Extraneural perineurioma: Usually arises in soft tissue but can have cutaneous examples; presents as firm, flesh-colored, superficial nodules, typically ranging from 0.5 to 1.5 cm in diameter. Most common locations are the leg or trunk.
A 40-year-old patient presents with a slow-growing, painless nodule on the finger. Histopathology shows a multilobulated tumor with abundant myxoid matrix and epithelioid Schwann cells. What is the diagnosis and recurrence rate?
The diagnosis is a nerve sheath myxoma. The recurrence rate is approximately 50% after incomplete excisions.
A patient with NF-1 presents with a bag-like mass along a nerve segment, described as feeling like a ‘bag of worms’ on palpation. What is the diagnosis and its potential complication?
The diagnosis is plexiform neurofibroma. The potential complication is malignant transformation into a malignant peripheral nerve sheath tumor (MPNST).
A patient presents with a soft, rubbery, skin-colored nodule that invaginates on pressure. What is the diagnosis and its histological features?
The diagnosis is localized neurofibroma. Histological features include a dermal-centered, nonencapsulated proliferation of Schwann cells, perineurial cells, and fibroblasts in a collagenous matrix.
A patient presents with a slow-growing, painless nodule on the extremity. Histopathology shows a multilobulated tumor with abundant myxoid matrix. What is the diagnosis and its histological markers?
The diagnosis is nerve sheath myxoma. Histological markers include S-100 protein and glial fibrillary acidic protein.
What is the diagnosis for a patient with NF-1 presenting with a bag-like mass along a nerve segment, feeling like a ‘bag of worms’ on palpation?
The diagnosis is plexiform neurofibroma.
Potential complication is malignant transformation into a malignant peripheral nerve sheath tumor (MPNST).
What is the diagnosis for a patient presenting with a soft, rubbery, skin-colored nodule that invaginates on pressure?
The diagnosis is localized neurofibroma.
Histological features include a dermal-centered, nonencapsulated proliferation of Schwann cells, perineurial cells, and fibroblasts in a collagenous matrix.
What is the diagnosis for a patient with a slow-growing, painless nodule on the extremity with histopathology showing a multilobulated tumor with abundant myxoid matrix?
The diagnosis is nerve sheath myxoma.
Histological markers include S-100 protein and glial fibrillary acidic protein.
What are the histopathological features of Malignant Peripheral Nerve Sheath Tumors (MPNSTs)?
- Intraneural: Circumscribed nonencapsulated proliferations of delicate spindle cells with elongated, bipolar cytoplasmic processes.
- Cellular arrangement: Small aggregates and bundles with individual cells oriented parallel to each other or forming small whorls.
- Sclerosing perineurioma: Heavily collagenous background.
- Reticular (retiform): Composed of anastomosing cords of fusiform cells wrapping around islands of fibromyxoid stroma.
- Epithelioid: Composed of epithelioid cells with eosinophilic cytoplasm.
- Staining: Positive for EMA and negative for S-100 and neurofilament; most cases express GLUT1 and claudin-1.
What are the clinical findings associated with Malignant Peripheral Nerve Sheath Tumors (MPNSTs)?
- Arise predominantly in deep soft tissues of the proximal extremities and present as enlarging masses.
- Pain is more prevalent in patients with Neurofibromatosis type 1 (NF-1).
- Sudden enlargement of a longstanding tumor should raise suspicion of malignant transformation.
What is the prognosis for patients with Malignant Peripheral Nerve Sheath Tumors (MPNSTs)?
- High-grade sarcomas with a high tendency for local recurrence and distant metastasis.
- Local recurrence occurs in approximately 40% of cases; metastases occur in 40% to 60% of patients within 12 months of surgery.
- 5-year survival rates range from 50% in sporadic patients to 10% to 35% in NF-1 patients.
What are the differential diagnoses for Malignant Peripheral Nerve Sheath Tumors (MPNSTs)?
- Clinically: Neurofibroma, schwannoma, lipoma, and cyst.
- Histopathologically: Desmoplastic melanoma, cellular schwannoma, and a variety of sarcomas including synovial sarcoma, leiomyosarcoma, RMS, adult-type fibrosarcoma, dedifferentiated liposarcoma, and clear-cell sarcoma.
What are the key features of Primitive Neuroectodermal Tumors (PNETs)?
- Median age at diagnosis is 9 years.
- Composed of small round cells of neuroectodermal origin.
- Can metastasize to the skin; most peripheral PNETs/Ewing sarcomas are located in deep soft tissue.
- With neuroblastoma, cutaneous metastases can be numerous and involve multiple sites, with initial presentation in 50% of cases.
What is the diagnosis for a patient with NF-1 presenting with a rapidly enlarging, painful mass in the proximal extremity?
The diagnosis is a malignant peripheral nerve sheath tumor (MPNST).
Prognosis is poor, with a high tendency for local recurrence and distant metastasis.
What is the diagnosis for a patient presenting with a firm, flesh-colored nodule on the leg with spindle cells and concentric whorls around axons?
The diagnosis is perineurioma.
Histological markers include EMA positivity and negativity for S-100 and neurofilament.
What are the histopathological features of Granular Cell Tumors?
Granular Cell Tumors (GCTs) exhibit the following histopathological features:
- Ill-defined, dermal-based, nodular proliferations composed of sheets of large polyhedral cells.
- Cells have distinct cell borders, small, round, central nuclei, and abundant fine to coarsely granular cytoplasm.
- Typically express S-100 protein, CD68, NGFR-5, MITF, NK1-C3, neuron-specific enolase, and PGP9.5.
- Atypical GCTs may show spindling of tumor cells, necrosis, diffuse pleomorphism, prominent nucleoli, high nuclear-to-cytoplasmic ratio, and mitotic activity greater than 2 per 10 HPF.
What is the clinical course and prognosis for benign and atypical Granular Cell Tumors?
- Benign and atypical GCTs: Excellent outcome with no metastasis.
- Malignant GCTs: Local recurrence and metastasis are common.
What are the clinical findings associated with Neuroglial Heterotopia?
- Solitary, firm, papule, often vascular appearing.
- Most commonly located in or on the nose.
- Can also be present on the face, scalp, lip, tongue, oropharynx, nasopharynx, or orbit.
What is the management approach for Meningeal Heterotopia?
The management approach for Meningeal Heterotopia typically involves:
- Local surgical excision, especially if lesions are symptomatic or connected to intracranial structures.
What are the differential diagnoses for Granular Cell Tumors?
- Clinical: Adnexal tumors, melanocytic nevi, dermatofibroma, and SCC of the tongue.
- Histopathological: Dermatofibroma, leiomyosarcoma, melanoma, and angiosarcoma.
What is the diagnosis for a 9-year-old child with a deep soft tissue mass and histopathology revealing small, round, basophilic cells with Homer Wright rosettes?
The diagnosis is a primitive neuroectodermal tumor (PNET).
The genetic marker is the MIC2 gene product, CD99.
What is the diagnosis for a patient presenting with a dermal-based nodule composed of large polyhedral cells with granular cytoplasm?
The diagnosis is granular cell tumor (GCT).
Histological markers include S-100 protein, CD68, and neuron-specific enolase.
What is the diagnosis for a patient presenting with a solitary, firm, vascular-appearing papule on the nose with mature neuroglial tissue?
The diagnosis is neuroglial heterotopia (nasal glioma).
Management includes local surgical excision.
What is the clinical presentation of myxopapillary ependymoma?
It presents as subcutaneous masses, often asymptomatic, in young patients, typically located in the sacrococcygeal region or gluteal area, and can reach several centimeters in size.
What is the diagnosis for a patient presenting with a skin-colored nodule on the scalp over the midline, surrounded by a ring of long, dark hair?
The diagnosis is meningeal heterotopia (rudimentary meningocele).
Management includes radiographic imaging before biopsy or excision, followed by surgical excision.
What is the diagnosis for a patient presenting with a sacrococcygeal mass that is asymptomatic with histopathology revealing papillae covered by ependymal cells?
The diagnosis is myxopapillary ependymoma.
It is usually benign, but the subcutaneous type has a higher risk of local recurrence and metastasis.
