Orthopedic MCQs: Schwannoma & Neurofibroma Pathology

Question 1

A 45-year-old male presents with a slowly enlarging, painless mass on the volar aspect of his forearm. Excisional biopsy reveals a well-encapsulated tumor with alternating hypercellular and hypocellular regions. The hypercellular regions feature spindle cells with palisading nuclei. What is the classic name for these palisading nuclear arrangements?

Explanation

Verocay bodies are formed by palisading nuclei in the hypercellular Antoni A regions of a schwannoma. They are highly characteristic of this benign nerve sheath tumor.

Question 2

During surgical exploration for a mass in the popliteal fossa causing mild paresthesias, the surgeon encounters an encapsulated mass eccentrically located on the tibial nerve. The nerve fascicles are splayed over the capsule. What is the most appropriate surgical management?

Explanation

Schwannomas grow eccentrically and are surrounded by a true capsule (epineurium), displacing the nerve fascicles. They can typically be safely shelled out (marginal enucleation) while preserving the continuity and function of the nerve.

Question 3

Which of the following macroscopic and microscopic growth patterns best differentiates a solitary neurofibroma from a schwannoma?

Explanation

Neurofibromas grow centrally and intimately involve the nerve fascicles, lacking a true capsule. Unlike schwannomas, they cannot be easily enucleated without sacrificing the involved nerve.

Question 4

A 22-year-old female with known Neurofibromatosis type 1 (NF1) presents with rapid enlargement of a long-standing "bag of worms" mass in her thigh. Which specific type of benign nerve sheath tumor carries the highest risk of malignant transformation in this patient?

Explanation

Plexiform neurofibromas are pathognomonic for NF1 and have a 5-10% lifetime risk of transforming into a Malignant Peripheral Nerve Sheath Tumor (MPNST). Cutaneous neurofibromas do not carry this malignant potential.

Question 5

Neurofibromatosis type 1 (von Recklinghausen disease) is an autosomal dominant disorder associated with multiple neurofibromas. Which of the following details the correct genetic mutation and corresponding gene product?

Explanation

NF1 is caused by a mutation on chromosome 17, which encodes the tumor suppressor protein neurofibromin. NF2 is associated with chromosome 22 and the protein merlin (schwannomin).

Question 6

A 30-year-old male is diagnosed with Neurofibromatosis type 2 (NF2). He is at highest risk for developing which of the following pathognomonic lesions?

Explanation

The hallmark of NF2 is the development of bilateral vestibular schwannomas (acoustic neuromas). NF1 is associated with plexiform neurofibromas, optic gliomas, and tibial pseudarthrosis.

Question 7

On physical examination of a patient with a suspected benign peripheral nerve sheath tumor in the upper extremity, which of the following findings is most characteristic?

Explanation

Benign nerve sheath tumors (like schwannomas and neurofibromas) are typically mobile transversely across the nerve but are restricted longitudinally because they are tethered to the nerve itself.

Question 8

Immunohistochemical staining is performed on a biopsy of a suspected peripheral nerve sheath tumor. Which staining pattern most strongly supports a diagnosis of schwannoma over neurofibroma?

Explanation

Schwannomas are composed almost entirely of neoplastic Schwann cells and show strong, diffuse positivity for S-100. Neurofibromas have a mixed cell population and typically show only patchy or weak S-100 staining.

Question 9

Histological evaluation of a nerve sheath tumor reveals alternating Antoni A and Antoni B areas. Which of the following best describes the microscopic appearance of the Antoni B areas?

Explanation

Antoni B areas in a schwannoma are hypocellular, loosely textured, and rich in a myxoid, edematous stroma. Antoni A areas are hypercellular with compact spindle cells.

Question 10

Which of the following microscopic features is a classic hallmark of a neurofibroma?

Explanation

Neurofibromas are characterized microscopically by wavy spindle cells (buckled nuclei) in a variably myxoid/collagenous background, frequently accompanied by numerous mast cells.

Question 11

A patient with NF1 has a known plexiform neurofibroma. Which of the following clinical changes is the most ominous sign suggesting malignant transformation to an MPNST?

Explanation

Malignant transformation of a plexiform neurofibroma to a Malignant Peripheral Nerve Sheath Tumor (MPNST) is clinically signaled by rapid growth, new-onset firm consistency, and intractable pain at rest.

Question 12

Magnetic Resonance Imaging (MRI) of a benign nerve sheath tumor often reveals the "target sign." What MRI characteristics define this sign?

Explanation

The "target sign" on T2-weighted MRI consists of peripheral hyperintensity (representing myxoid Antoni B tissue) and central hypointensity (representing fibrocollagenous Antoni A tissue). It strongly suggests a benign nerve sheath tumor.

Question 13

A 14-year-old boy presents with a massive, diffuse, tortuous swelling of his right upper extremity. Palpation of the mass yields a sensation described as a "bag of worms." This lesion is considered pathognomonic for which condition?

Explanation

The "bag of worms" palpation refers to a plexiform neurofibroma. This lesion involves multiple nerve fascicles and branches, and is strictly pathognomonic for Neurofibromatosis type 1 (NF1).

Question 14

A 50-year-old male is diagnosed with a high-grade Malignant Peripheral Nerve Sheath Tumor (MPNST) of the sciatic nerve. Staging shows no metastasis. What is the mainstay of definitive surgical treatment?

Explanation

MPNST is a highly aggressive sarcoma. The standard of care is wide surgical resection with negative margins, which almost always necessitates sacrificing the involved nerve. Neoadjuvant or adjuvant radiation is often utilized.

Question 15

A patient presents with multiple distinct schwannomas in the extremities but lacks vestibular schwannomas. Genetic testing reveals a mutation distinct from NF1 and NF2. Which gene is most commonly implicated in this condition (Schwannomatosis)?

Explanation

Schwannomatosis is a distinct clinical entity from NF1 and NF2, characterized by multiple schwannomas without bilateral acoustic neuromas. It is most commonly associated with mutations in the SMARCB1 (INI1) or LZTR1 genes.

Question 16

A 40-year-old patient presents with a biopsy-confirmed solitary schwannoma of the median nerve. The patient is anxious about the mass becoming malignant. What is the approximate risk of malignant transformation for a solitary schwannoma?

Explanation

Unlike neurofibromas (specifically the plexiform type in NF1), solitary schwannomas have virtually no risk of malignant transformation. They are completely benign lesions.

Question 17

A 3-year-old child presents with anterolateral bowing of the tibia. Radiographs show medullary sclerosis and cortical thinning. If this child has an underlying genetic syndrome, which of the following is the most likely associated nerve sheath tumor pathology?

Explanation

Anterolateral tibial bowing (and subsequent pseudarthrosis) is a classic orthopedic manifestation of NF1. The characteristic nerve sheath tumor associated with NF1 is the neurofibroma, notably the plexiform neurofibroma.

Question 18

During histologic review of an aggressive spindle cell sarcoma arising from a major nerve, the pathologist suspects an MPNST. Compared to a benign schwannoma, what change in S-100 immunohistochemical staining is expected in an MPNST?

Explanation

As malignant peripheral nerve sheath tumors (MPNST) de-differentiate, they typically lose the strong, diffuse S-100 positivity seen in benign nerve sheath tumors, resulting in patchy, weak, or negative S-100 staining.

Question 19

A 12-year-old boy is suspected of having Neurofibromatosis type 1. Which of the following is an established clinical diagnostic criterion for NF1 according to the NIH guidelines?

Explanation

The NIH diagnostic criteria for NF1 require at least two features, one of which can be the presence of 6 or more café-au-lait spots (measuring >5 mm in prepubertal individuals and >15 mm in postpubertal individuals).

Question 20

Which of the following describes the cellular composition of a neurofibroma compared to a schwannoma?

Explanation

Neurofibromas are heterogeneous, unencapsulated tumors containing Schwann cells, fibroblasts, perineurial-like cells, and mast cells admixed with axons. In contrast, schwannomas are predominantly homogeneous proliferations of neoplastic Schwann cells.

Question 21

A 45-year-old female presents with a slow-growing volar forearm mass. The mass is mobile transversely but not longitudinally. Histologic examination reveals a biphasic architecture with hypercellular areas of nuclear palisading and hypocellular myxoid areas. What is the most likely diagnosis?

Explanation

The clinical presentation and histology (Antoni A hypercellular areas with nuclear palisading and Antoni B hypocellular areas) are pathognomonic for a schwannoma. Schwannomas are encapsulated and typically displace nerve fascicles eccentrically.

Question 22

A 30-year-old male with known Neurofibromatosis Type 1 (NF1) presents with a rapidly enlarging, painful mass in his thigh. Biopsy demonstrates a high mitotic rate, necrosis, and marked nuclear pleomorphism. Which of the following is the most likely precursor lesion for this malignancy?

Explanation

This patient has developed a Malignant Peripheral Nerve Sheath Tumor (MPNST). In patients with NF1, MPNSTs almost exclusively arise from pre-existing plexiform neurofibromas rather than solitary or cutaneous variants.

Question 23

During surgical exploration of a peripheral nerve tumor, the surgeon notes the mass is encapsulated and located eccentrically, allowing the continuous nerve fascicles to be carefully peeled away from the tumor capsule. What is the recommended surgical management?

Explanation

The intraoperative finding of an eccentric, encapsulated tumor that spares the nerve fascicles is characteristic of a schwannoma. The standard treatment is marginal enucleation, preserving the parent nerve.

Question 24

A 25-year-old male presents with a central, fusiform enlargement of the median nerve. Histology reveals spindle cells in a myxoid stroma with "shredded carrot" collagen, and the mass cannot be separated from the nerve fascicles. The mutated gene responsible for this condition normally performs which of the following functions?

Explanation

The description is classic for a neurofibroma, associated with NF1. The NF1 gene produces neurofibromin, a GTPase-activating protein that downregulates the RAS signaling pathway.

Question 25

Which of the following describes the characteristic "target sign" frequently observed on T2-weighted MRI of benign peripheral nerve sheath tumors?

Explanation

The MRI "target sign" on T2-weighted imaging features central hypointensity (corresponding to dense fibrocollagenous tissue) and peripheral hyperintensity (corresponding to myxoid tissue). It is highly suggestive of benign neurogenic tumors like schwannomas.

Question 26

An 18-year-old female presents with bilateral hearing loss, multiple cutaneous schwannomas, and meningiomas. The defective protein in her underlying condition normally localizes to which of the following cellular areas?

Explanation

The patient has Neurofibromatosis Type 2 (NF2), caused by a mutation in the NF2 gene on chromosome 22. This gene encodes merlin (schwannomin), a tumor suppressor protein that links actin filaments to cell membrane proteins.

Question 27

Immunohistochemical staining is performed on a suspected peripheral nerve sheath tumor to differentiate between a schwannoma and a neurofibroma. Which staining profile most strongly supports a diagnosis of a schwannoma?

Explanation

Schwannomas are composed almost entirely of Schwann cells, resulting in diffuse and strong S-100 and SOX10 positivity. Neurofibromas contain a mix of cell types, leading to patchy S-100 staining and CD34 positivity in the stromal network.

Question 28

A 35-year-old patient presents with multiple painful peripheral schwannomas but lacks bilateral vestibular schwannomas. Genetic testing reveals a mutation in the SMARCB1 (INI1) gene. What is the most likely diagnosis?

Explanation

Schwannomatosis is a distinct genetic condition characterized by multiple schwannomas without the vestibular involvement seen in NF2. It is typically associated with mutations in the SMARCB1 (INI1) or LZTR1 genes.

Question 29

During the histopathological review of an excised peripheral soft tissue mass, the pathologist identifies Verocay bodies. What do these specific structures consist of?

Explanation

Verocay bodies are characteristic histologic features found in the Antoni A areas of schwannomas. They consist of stacked, parallel rows of palisading nuclei separated by pink, anucleate zones of cytoplasmic processes.

Question 30

What is the approximate lifetime risk of a plexiform neurofibroma undergoing malignant transformation to an MPNST in a patient with Neurofibromatosis type 1?

Explanation

Patients with NF1 have an estimated 8% to 13% lifetime risk of developing a Malignant Peripheral Nerve Sheath Tumor (MPNST). These nearly always arise from pre-existing plexiform neurofibromas.

Question 31

A 40-year-old male presents with a painless, slow-growing mass in the posterior thigh. MRI reveals a "split-fat" sign and a "fascicular" sign within the lesion. Which of the following is true regarding its management?

Explanation

The "split-fat" and "fascicular" signs on MRI are characteristic of benign peripheral nerve sheath tumors, most commonly schwannomas. They can typically be treated with marginal enucleation, preserving the continuity of the parent nerve.

Question 32

Which of the following clinical or anatomical characteristics accurately differentiates a solitary neurofibroma from a schwannoma?

Explanation

Neurofibromas grow intrinsically within the nerve, intertwining with and separating the nerve fascicles, making nerve-sparing resection difficult. Schwannomas grow eccentrically and push the fascicles aside beneath a true capsule.

Question 33

A 35-year-old female presents with a growing mass in her popliteal fossa. Histology demonstrates a variable mix of Schwann cells, fibroblasts, and perineurial cells, with mast cells scattered among spindle cells with wavy nuclei. What is the most likely diagnosis?

Explanation

The presence of a heterogeneous cell population (Schwann cells, fibroblasts, mast cells) with wavy, "buckled" nuclei is the classic histologic description of a neurofibroma. Schwannomas are more homogenous.

Question 34

In a patient with Neurofibromatosis Type 1, which skeletal manifestation is considered a characteristic diagnostic criterion?

Explanation

Anterolateral tibial bowing (often progressing to congenital pseudarthrosis of the tibia) is a classic skeletal manifestation and a diagnostic criterion for NF1. Posteromedial bowing is typically associated with calcaneovalgus foot deformity and resolves spontaneously.

Question 35

A biopsy of a rapidly expanding peripheral nerve tumor in a patient with NF1 shows complete loss of H3K27me3 expression on immunohistochemistry. This finding is highly specific for which of the following?

Explanation

Loss of trimethylation at lysine 27 of histone H3 (H3K27me3) is a highly specific and sensitive immunohistochemical marker for MPNST. It helps differentiate MPNST from benign nerve sheath tumors and other high-grade sarcomas.

Question 36

When attempting to surgically resect a major nerve plexiform neurofibroma that is causing severe intractable pain and progressive motor deficit, the surgeon should counsel the patient on which expected outcome?

Explanation

Plexiform neurofibromas grow infiltratively among the fascicles of multiple nerve branches. Resection inevitably requires sacrificing functional nerve tissue, carrying a high risk of permanent neurologic deficit.

Question 37

Which of the following is the most appropriate initial management for an asymptomatic, small (1.5 cm), solitary neurofibroma of the ulnar nerve found incidentally on MRI?

Explanation

Incidental, asymptomatic, small benign peripheral nerve sheath tumors (like solitary neurofibromas) should be managed with observation. Surgical intervention risks iatrogenic nerve injury and should be reserved for symptomatic or growing lesions.

Question 38

The "target sign" seen on T2-weighted MRI of a schwannoma corresponds histologically to which of the following spatial arrangements?

Explanation

The T2 target sign represents a central area of low signal intensity (highly cellular Antoni A tissue with dense collagen) surrounded by a peripheral rim of high signal intensity (myxoid, hypocellular Antoni B tissue).

Question 39

A 50-year-old male undergoes marginal enucleation of a solitary schwannoma of the sciatic nerve. Postoperatively, he experiences neuropraxia in the distribution of the peroneal division. What is the most likely cause of this complication?

Explanation

Neuropraxia following enucleation of a schwannoma is common and typically results from surgical traction on the true nerve fascicles stretched over the tumor capsule. Function usually recovers over weeks to months.

Question 40

Which of the following diagnostic criteria is sufficient to establish a definitive clinical diagnosis of Neurofibromatosis Type 2 (NF2)?

Explanation

Bilateral vestibular schwannomas are the hallmark of NF2 and are sufficient alone to make the diagnosis. The other options listed (optic glioma, café-au-lait spots, freckling, tibial pseudarthrosis) are diagnostic criteria for NF1.

Question 41

A 45-year-old female presents with a slow-growing, painful mass in her volar forearm. MRI shows a well-circumscribed lesion eccentrically located on the median nerve. During exploration, the mass is easily shelled out without damaging the nerve fascicles. Which of the following histologic features is most likely present?

Explanation

The clinical and surgical presentation describes a schwannoma, which is encapsulated and eccentric, allowing for enucleation. Histologically, schwannomas are characterized by alternating cellular (Antoni A with Verocay bodies) and hypocellular (Antoni B) areas.

Question 42

A 28-year-old male with known Neurofibromatosis type 1 presents with rapid enlargement and new-onset severe rest pain in a long-standing thigh mass. What is the most appropriate next step in management?

Explanation

Rapid growth and severe pain in a pre-existing plexiform neurofibroma in an NF1 patient strongly suggest malignant transformation to a Malignant Peripheral Nerve Sheath Tumor (MPNST). A biopsy is required to confirm the diagnosis before planning definitive wide resection.

Question 43

A surgical pathology report for a resected peripheral nerve tumor describes unencapsulated spindle cells intermingled with nerve fibers and thick, wavy collagen bundles resembling "shredded carrots." Which of the following is most accurate regarding this lesion?

Explanation

The histology describes a neurofibroma. Unlike schwannomas, neurofibromas are intimately intermingled with the nerve fascicles, meaning complete surgical excision typically requires sacrificing the involved nerve segment.

Question 44

A 6-year-old child presents with anterolateral bowing of the tibia. Examination reveals six café-au-lait macules and axillary freckling. The underlying genetic mutation for this patient's condition affects a gene located on which chromosome?

Explanation

The patient has Neurofibromatosis type 1, indicated by tibial pseudarthrosis, café-au-lait spots, and axillary freckling. NF1 is caused by a mutation in the neurofibromin gene located on chromosome 17.

Question 45

A 30-year-old female presents with bilateral hearing loss, balance issues, and a palpable mass on her left ulnar nerve. MRI of the brain reveals bilateral vestibular tumors. The mutated gene in this syndrome encodes for which of the following proteins?

Explanation

The patient has Neurofibromatosis type 2, characterized by bilateral vestibular schwannomas. NF2 is caused by a mutation on chromosome 22, which encodes the tumor suppressor protein merlin (also known as schwannomin).

Question 46

On T2-weighted MRI, a benign peripheral nerve sheath tumor exhibits a "target sign" with peripheral hyperintensity and central hypointensity. The lesion is eccentric to the nerve. Which of the following immunohistochemical markers will be strongly and diffusely positive?

Explanation

The MRI "target sign" and eccentric location are classic for a schwannoma. Schwannomas are of neural crest origin and stain strongly and diffusely positive for S-100 protein.

Question 47

A 42-year-old patient with NF-1 is diagnosed with a high-grade Malignant Peripheral Nerve Sheath Tumor (MPNST) of the sciatic nerve. Which of the following factors carries the worst prognostic implication for overall survival in this patient?

Explanation

In patients with MPNST, the presence of an underlying NF-1 diagnosis is associated with a significantly worse prognosis and decreased overall survival compared to sporadic cases. Large tumor size and incomplete surgical margins also confer a poor prognosis.

Question 48

During microscopic examination of an enucleated peripheral nerve mass, the pathologist notes palisading nuclei surrounding eosinophilic, anuclear zones of cellular processes. What is the eponym for this specific histologic structure?

Explanation

Verocay bodies are formed by palisading nuclei surrounding anuclear zones and are characteristic of Antoni A areas in schwannomas. This is a classic distinguishing histological feature of this benign nerve sheath tumor.

Question 49

A 55-year-old male incidentally discovers a 2 cm painless, mobile mass in the medial aspect of his arm. Ultrasound demonstrates a well-defined, hypoechoic lesion eccentric to the ulnar nerve with posterior acoustic enhancement. Neurological exam is normal. What is the most appropriate initial management?

Explanation

The clinical and sonographic findings are highly suggestive of an asymptomatic benign schwannoma. Because malignant transformation is exceptionally rare and surgery carries a risk of iatrogenic nerve injury, observation is the most appropriate initial management.

Question 50

A mass excised from a 12-year-old boy's brachial plexus reveals enlarged, tortuous nerve fascicles grossly resembling a "bag of worms." Histologically, the lesion expands the nerve fascicles. Which of the following is true regarding this tumor type?

Explanation

A "bag of worms" appearance describes a plexiform neurofibroma, which is pathognomonic for NF-1. These tumors carry an approximately 5-10% lifetime risk of transforming into a Malignant Peripheral Nerve Sheath Tumor (MPNST).

Question 51

A patient presents with a soft tissue mass in the popliteal fossa. Palpation of the mass elicits paresthesias radiating to the plantar aspect of the foot. Which of the following signs is being demonstrated, indicating a neural origin of the tumor?

Explanation

Tinel's sign over a soft tissue mass indicates that the tumor involves a peripheral nerve. Tapping or palpating the mass mechanically stimulates the nerve, causing distal paresthesias in the nerve's distribution.

Question 52

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) most commonly arise from which of the following cellular components of the peripheral nerve?

Explanation

MPNSTs are malignant sarcomas of neural crest origin that primarily differentiate toward, and arise from, Schwann cells. They often occur in the setting of pre-existing plexiform neurofibromas in NF-1 patients.

Question 53

A surgeon is performing an excision of a confirmed median nerve schwannoma. To minimize the risk of permanent neurologic deficit, the longitudinal incision through the epineurium should be made in which location?

Explanation

Excision of a schwannoma requires a longitudinal epineurotomy in a "safe zone" devoid of traversing nerve fascicles. Careful microscopic dissection allows the encapsulated tumor to be shelled out while preserving functional motor and sensory fascicles.

Question 54

A 40-year-old male without systemic disease presents with a solitary, slow-growing, mildly tender cutaneous mass on his trunk. Biopsy reveals a well-circumscribed but unencapsulated proliferation of S-100 positive spindle cells with wavy nuclei in a collagenous stroma. No other lesions are present. What is the risk of malignant transformation for this specific lesion?

Explanation

The patient has a sporadic, localized cutaneous neurofibroma. Unlike plexiform neurofibromas associated with NF-1, solitary cutaneous neurofibromas have virtually zero (less than 1%) risk of malignant transformation.

Question 55

A 35-year-old female with known NF-1 presents for routine MRI surveillance of a massive sciatic plexiform neurofibroma. Which of the following MRI findings would be most highly suspicious for malignant transformation to an MPNST?

Explanation

Findings suggesting malignant transformation include rapid growth, perilesional edema, ill-defined margins (suggesting local invasion), and cystic or necrotic changes. The "target sign" and "split-fat sign" are typical of benign peripheral nerve sheath tumors.

Question 56

In addition to spindle-shaped Schwann cells and fibroblasts, which inflammatory cell type is frequently abundant in the stroma of a neurofibroma and is thought to play a role in tumor growth and pain generation?

Explanation

Mast cells are characteristically abundant in the myxoid stroma of neurofibromas. They are believed to secrete mediators that promote tumor angiogenesis, fibroblast proliferation, and the typical pain or pruritus associated with these tumors.

Question 57

An 8-year-old boy with NF-1 is referred to orthopedics. Which of the following spinal deformities is most characteristic of this condition and typically requires early, aggressive surgical intervention?

Explanation

Dystrophic kyphoscoliosis in NF-1 is characterized by a short, sharply angulated curve with severe vertebral wedging, spindling of the transverse processes, and dural ectasia. It progresses rapidly and usually requires combined anterior and posterior spinal fusion.

Question 58

Following successful enucleation of a 3 cm benign schwannoma from the posterior interosseous nerve, the patient exhibits a new-onset wrist and finger drop. The surgeon is certain no fascicles were sharply transected. What is the most likely etiology and expected outcome of this deficit?

Explanation

Transient neurologic deficits (neuropraxia) are common after schwannoma enucleation due to traction and manipulation of the adjacent nerve fascicles. If the fascicles were anatomically preserved, spontaneous recovery over weeks to months is the expected outcome.

Question 59

A 65-year-old female undergoes resection of a deep seated, long-standing retroperitoneal schwannoma. The pathology report notes degenerative changes including cyst formation, calcification, and nuclear atypia without mitotic figures. This histologic pattern is commonly referred to as:

Explanation

"Ancient schwannoma" is a benign variant characterized by degenerative changes such as cyst formation, calcification, hemorrhage, and marked nuclear atypia. The absence of mitotic figures and necrosis differentiates it from a true malignancy.

Question 60

A 45-year-old female presents with a slow-growing, painful mass in her volar forearm. Excisional biopsy reveals an encapsulated tumor with alternating hypercellular and hypocellular areas. The hypercellular areas feature palisading nuclei around fibrillary processes. What is the most likely diagnosis?

Explanation

The description highlights Antoni A (hypercellular with Verocay bodies) and Antoni B (hypocellular) areas, classic for a Schwannoma. Schwannomas are encapsulated and eccentric to the nerve fascicles.

Question 61

When evaluating a peripheral nerve sheath tumor using MRI, the "target sign" is frequently observed on T2-weighted images. What histologic features correspond to this radiographic appearance?

Explanation

The T2 target sign reflects a low-signal center of dense fibrous collagenous tissue and a high-signal periphery of water-rich myxoid tissue. It is commonly seen in both neurofibromas and schwannomas.

Question 62

A 30-year-old male with a known genetic disorder presents with a massive, tortuous, "bag of worms" soft tissue mass along his sciatic nerve. He complains of new-onset severe pain and rapidly progressive foot drop. What is the most likely underlying genetic mutation?

Explanation

The patient has a plexiform neurofibroma ("bag of worms"), which is pathognomonic for Neurofibromatosis type 1 (NF1). The new pain and motor deficit suggest malignant transformation to MPNST.

Question 63

A surgeon is planning the excision of a symptomatic solitary peripheral nerve sheath tumor located in the median nerve. Preoperative imaging suggests a schwannoma. Which of the following describes the most appropriate surgical approach?

Explanation

Schwannomas grow eccentrically and displace nerve fascicles to the periphery. They can typically be treated with longitudinal epineurotomy and careful marginal enucleation, preserving nerve function.

Question 64

Histologic evaluation of a resected peripheral nerve sheath tumor demonstrates unencapsulated proliferation of spindle cells, an abundant myxoid matrix, interwoven nerve fascicles, and "shredded carrot" collagen bundles. Which of the following is true regarding this lesion?

Explanation

The histology describes a neurofibroma. Unlike schwannomas, neurofibromas grow intrinsically among the nerve fascicles, meaning surgical resection typically requires sacrifice of the involved nerve segment.

Question 65

A patient with bilateral vestibular schwannomas and multiple peripheral nerve tumors is being evaluated. Which of the following proteins is deficient or defective in this patient's underlying syndrome?

Explanation

Bilateral vestibular schwannomas are the hallmark of Neurofibromatosis type 2 (NF2). This disorder is caused by a mutation in the NF2 gene on chromosome 22q12, which encodes the protein merlin.

Question 66

During physical examination of an upper extremity soft tissue mass suspected to be a peripheral nerve sheath tumor, the clinician elicits Valleix's sign. Which clinical finding best describes the mobility of these tumors?

Explanation

Peripheral nerve sheath tumors are tethered to the nerve of origin. Consequently, they are mobile perpendicular (transversely) to the axis of the nerve but restricted parallel (longitudinally) to it.

Question 67

A 35-year-old male with Schwannomatosis presents with multiple painful peripheral nerve tumors. Which gene mutations are most commonly implicated in the pathogenesis of familial Schwannomatosis in the absence of bilateral vestibular schwannomas?

Explanation

Schwannomatosis is distinct from NF1 and NF2 and is characterized by multiple painful schwannomas without vestibular involvement. It is frequently associated with mutations in the SMARCB1 and LZTR1 genes.

Question 68

A pathologist is using a neurofilament stain to differentiate between a schwannoma and a neurofibroma. Which pattern of axonal staining strongly favors the diagnosis of a schwannoma?

Explanation

Schwannomas are encapsulated and push the native nerve fascicles outward. A neurofilament stain will show axons draped over the peripheral capsule, whereas in a neurofibroma, axons traverse through the tumor mass.

Question 69

A 22-year-old with NF1 has a known large plexiform neurofibroma of the thigh. He reports a 2-month history of rapid tumor enlargement and new, unrelenting rest pain. What is the most appropriate next step in management?

Explanation

Rapid growth and new pain in a plexiform neurofibroma strongly suggest malignant transformation to an MPNST. An FDG-PET/CT helps identify the most metabolically active areas to target for biopsy.

Question 70

Which of the following immunohistochemical staining profiles is most characteristic of a benign sporadic schwannoma?

Explanation

Schwannomas are composed entirely of neoplastic Schwann cells, showing strong, diffuse, and uniform positivity for S-100 and SOX10. Neurofibromas exhibit only patchy S-100 staining due to their mixed cellular composition.

Question 71

What is the expected outcome regarding malignant transformation in a patient with a solitary, sporadic schwannoma of the ulnar nerve?

Explanation

Unlike plexiform neurofibromas in NF1, solitary sporadic schwannomas have an exceptionally low risk of malignant transformation, essentially considered zero in most clinical series.

Question 72

A 50-year-old patient undergoes uncomplicated marginal enucleation of a 3-cm median nerve schwannoma in the mid-forearm. Postoperatively, she experiences new numbness and tingling in the thumb and index finger without motor weakness. What is the most appropriate management?

Explanation

Transient sensory neuropraxia is common following schwannoma enucleation due to intraoperative manipulation and traction on the fascicles. It almost always resolves with conservative management and observation.

Question 73

Which of the following describes the characteristic gross pathological appearance and architectural relationship of a solitary intraneural neurofibroma to its parent nerve?

Explanation

Solitary intraneural neurofibromas present as fusiform, unencapsulated expansions of the nerve. The nerve fascicles pass directly through the substance of the tumor, making nerve-sparing resection nearly impossible.

Question 74

Which of the following clinical features most reliably distinguishes a malignant peripheral nerve sheath tumor (MPNST) from a benign neurofibroma?

Explanation

While benign nerve tumors can cause a Tinel's sign and have characteristic MRI features, rapid exponential growth, intractable rest pain, and new motor/sensory deficits are the clinical hallmarks of malignant transformation.

Question 75

A biopsy of a large sciatic nerve mass in an NF1 patient reveals pleomorphic spindle cells, frequent mitoses, necrosis, and loss of H3K27me3 expression. Which of the following best describes the prognosis and primary treatment?

Explanation

The biopsy shows an MPNST, a high-grade sarcoma associated with a poor prognosis. Treatment demands wide surgical resection, often combined with neoadjuvant or adjuvant radiation and chemotherapy.

Question 76

A 60-year-old female is incidentally found to have an asymptomatic 2-cm fusiform mass in the posterior tibial nerve on an MRI obtained for an ankle sprain. The mass has a target sign and biopsy confirms a benign neurofibroma. What is the most appropriate management?

Explanation

Asymptomatic, benign intraneural neurofibromas should be managed with observation. Resection would inevitably sacrifice the functional posterior tibial nerve, resulting in significant plantar sensory and motor loss.

Question 77

Under the microscope, a peripheral nerve sheath tumor displays Antoni A tissue. What specific microscopic structure, composed of palisading nuclei surrounding eosinophilic zones of cellular processes, is diagnostic of this region?

Explanation

Verocay bodies are highly characteristic of the Antoni A (hypercellular) areas of a schwannoma. They consist of stacked arrangements of elongated palisading nuclei alternating with anuclear fibrillary zones.

Question 78

What is the primary cellular origin of both Schwannomas and Neurofibromas?

Explanation

Both schwannomas and neurofibromas arise from Schwann cells, which are derived from the embryonic neural crest. Despite differing architectures and mixed cellularity in neurofibromas, the neoplastic driver is the Schwann cell.

Question 79

A 28-year-old patient with NF1 requires resection of a large, symptomatic, benign intraneural neurofibroma of the radial nerve. Which of the following preoperative discussions is most critical regarding expected postoperative outcomes?

Explanation

Because an intraneural neurofibroma incorporates the nerve fascicles within its substance, complete excision requires sacrificing that nerve segment. The patient must be prepared for the resulting functional loss and likely need for reconstruction.

Question 80

A 40-year-old patient presents with a slow-growing, painful mass in the volar forearm. Intraoperatively, the mass is found to be encapsulated and eccentrically located on the median nerve. Which of the following is the most likely intraoperative characteristic of this lesion?

Explanation

Schwannomas are typically eccentrically located and encapsulated, allowing for enucleation while sparing the nerve fascicles. Neurofibromas, in contrast, are usually centrally located and inextricably intertwined with the fascicles.

Question 81

A biopsy of a peripheral nerve sheath tumor reveals a biphasic architecture with hypercellular areas containing palisading nuclei and hypocellular, myxoid areas. What are the hypercellular regions with palisading nuclei commonly called?

Explanation

The hypercellular areas in a schwannoma are called Antoni A areas, which often contain palisading nuclei. Verocay bodies are specific formations of these palisading nuclei within the Antoni A regions.

Question 82

A 25-year-old patient with bilateral vestibular schwannomas is evaluated. This condition is associated with a mutation in a tumor suppressor gene. What is the correct gene and its chromosomal location?

Explanation

Bilateral vestibular schwannomas are the hallmark of Neurofibromatosis Type 2 (NF2). This condition is caused by a mutation in the merlin (schwannomin) gene located on chromosome 22.

Question 83

A patient with Neurofibromatosis Type 1 (NF1) presents with rapid enlargement and increasing pain in a long-standing plexiform neurofibroma. What is the most likely malignant transformation?

Explanation

Plexiform neurofibromas in NF1 carry a 5-10% lifetime risk of malignant transformation into Malignant Peripheral Nerve Sheath Tumors (MPNST). Rapid growth and pain are classic warning signs.

Question 84

Which of the following is the most appropriate surgical management for a solitary, symptomatic, centrally located neurofibroma involving a major motor nerve?

Explanation

Unlike schwannomas, solitary neurofibromas grow within the nerve, spreading apart the fascicles making them inseparable from the tumor. Removal typically requires segmental nerve resection and subsequent nerve grafting.

Question 85

On a T2-weighted MRI, a benign peripheral nerve sheath tumor demonstrates a "target sign" characterized by a hyperintense rim and a hypointense center. What histological feature corresponds to the central hypointensity?

Explanation

The MRI "target sign" in nerve sheath tumors shows a hyperintense rim (myxoid Antoni B tissue) and a hypointense center. The hypointense center corresponds to dense, cellular fibrocollagenous tissue (Antoni A areas).

Question 86

During physical examination, a plexiform neurofibroma is classically described as feeling like which of the following?

Explanation

Plexiform neurofibromas involve multiple fascicles of a nerve and its branches, creating a complex, irregular mass. On palpation, this is classically described as feeling like a "bag of worms."

Question 87

When utilizing immunohistochemistry to differentiate peripheral nerve sheath tumors from other soft tissue masses, which marker is strongly and uniformly positive in schwannomas?

Explanation

Schwannomas show strong and uniform positivity for S-100 protein due to their neural crest origin. Neurofibromas also stain for S-100, but typically in a more patchy and variable distribution.

Question 88

To establish a clinical diagnosis of Neurofibromatosis Type 1 (NF1) in a prepubertal child, the presence of cafe-au-lait macules is a major criterion. What is the minimum requirement for these macules?

Explanation

Diagnostic criteria for NF1 include six or more cafe-au-lait spots. They must measure greater than 5 mm in prepubertal individuals and greater than 15 mm in postpubertal individuals.

Question 89

Which of the following histological features best distinguishes a neurofibroma from a schwannoma?

Explanation

Neurofibromas grow interstitially among nerve fascicles, incorporating nerve fibers throughout the tumor matrix. Schwannomas are encapsulated and push nerve fibers to the periphery.

Question 90

Which of the following factors is considered the most significant poor prognostic indicator in a patient diagnosed with a Malignant Peripheral Nerve Sheath Tumor (MPNST)?

Explanation

MPNSTs associated with NF1 generally have a worse prognosis, higher recurrence rates, and higher mortality compared to sporadic MPNSTs. Large size and truncal location are also poor prognostic factors.

Question 91

A patient presents with multiple schwannomas without vestibular nerve involvement. Genetic testing for Schwannomatosis is most likely to reveal a mutation in which of the following genes?

Explanation

Schwannomatosis is a distinct clinical entity from NF1 and NF2, characterized by multiple schwannomas without bilateral vestibular involvement. It is genetically linked to mutations in the SMARCB1 (INI1) and LZTR1 genes.

Question 92

A 35-year-old female presents with a swelling in the medial aspect of her arm. Which of the following clinical findings is most characteristic of a schwannoma?

Explanation

Schwannomas often present as a slow-growing palpable mass. Tapping the mass frequently elicits a positive Tinel sign (paresthesias radiating along the nerve distribution).

Question 93

Which histological description is the classic hallmark of a neurofibroma?

Explanation

Neurofibromas are characterized by wavy, serpentine spindle cells (Schwann cells and fibroblasts) set in a myxoid stroma. They classically feature thick, ropey collagen bundles known as "shredded carrot" collagen.

Question 94

On an MRI of the thigh, a well-defined mass is surrounded by a rim of fat at the superior and inferior poles. This "split fat sign" is most indicative of which type of tumor?

Explanation

The "split fat sign" on MRI represents a layer of normal fat pushed to the proximal and distal poles of a mass as it grows within an intermuscular neurovascular bundle. It is highly characteristic of peripheral nerve sheath tumors like schwannomas.

Question 95

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) most commonly arise from which of the following pre-existing conditions?

Explanation

MPNSTs most frequently arise de novo or from the malignant transformation of a pre-existing plexiform neurofibroma in the setting of NF1. Solitary schwannomas have an exceedingly rare rate of malignant transformation.

Question 96

A surgeon successfully enucleates a peripheral nerve tumor, yielding a mass with a thick, distinct capsule. Postoperatively, the patient has no new motor deficits. The tumor was most likely a:

Explanation

Schwannomas possess a true epineural capsule and displace nerve fascicles peripherally, allowing for safe enucleation. Neurofibromas lack a true capsule and are intertwined with fascicles, making deficit-free enucleation nearly impossible.

Question 97

The "fascicular sign" on a T2-weighted MRI of a peripheral nerve tumor is best characterized by which of the following?

Explanation

The "fascicular sign" refers to the appearance of multiple small, ring-like structures within the tumor on MRI, representing individual thickened nerve fascicles. It is a hallmark of benign peripheral nerve sheath tumors.

Question 98

While schwannomas are composed almost exclusively of neoplastic Schwann cells, what cell type combination forms the primary neoplastic component of a neurofibroma?

Explanation

Neurofibromas are heterogeneous tumors consisting of neoplastic Schwann cells admixed with fibroblasts, perineurial-like cells, and often numerous mast cells. This distinguishes them from the monotypic Schwann cell population of a schwannoma.

Question 99

A 45-year-old with NF1 presents with a progressively enlarging, painful mass in the sciatic nerve distribution. Biopsy reveals spindle cells with high mitotic activity, necrosis, and marked pleomorphism. S-100 staining is patchy and weak. What is the most likely diagnosis?

Explanation

High mitotic activity, necrosis, and pleomorphism in a nerve tumor of an NF1 patient strongly indicate an MPNST. Unlike benign schwannomas (strongly S-100 positive), MPNSTs often show patchy, weak, or absent S-100 staining.

Orthopedic Board Review: Set 861 - 100 High-Yield MCQs

Orthopedic 2026 MCQs: Schwannoma & Neurofibroma Pathology | AAOS & ABOS Board Review

Key Takeaway

Orthopedic 2026 MCQs: Schwannoma & Neurofibroma Pathology | AAOS & ABOS Board Review

Chapter Index