Intramedullary spinal cord metastasis to the cauda equina in a patient with HER2-positive metastatic breast cancer: A case report.

The rate of metastasis to the central nervous system is high in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer patients. Metastatic cauda equina tumors are characterized by rapid progression of symptoms, thus signifying the requirement of their early treatment. However, these tumors are rarely reported, and their optimal treatment options have not been established yet. Here, we report a case study of a patient with HER2-positive breast cancer that metastasized to the cauda equina. The patient underwent urgent surgery to relieve the spinal cord compression. The pain in her back and lower limbs was greatly reduced. Unfortunately, her ability to walk did not improve sufficiently. Overall, surgical treatment may be a favorable option to improve a patient's quality of life.

Review of Perineural Invasion in Keratinocyte Carcinomas.

Perineural invasion is an infiltrative process of peripheral nerves by the primary neoplasm within the immediate vicinity. Aggressive forms of keratinocyte carcinomas, such as basal cell and squamous cell carcinomas, may feature perineural invasion, which is often associated with tumor recurrence and poorer prognosis. Diagnosis requires a high clinical suspicion. Imaging and histopathology are used to assess for extent of disease while surgical excision with complete circumferential peripheral and margin assessment is the treatment goal. However, there is still significant uncertainty about adjuvant chemotherapy and definitive management guidelines. Here, we summarize the current understanding of this complex pathogenic process, the clinical presentation, and the significance of perineural inflammation. We also discuss the recommendations about staging, prognosis, adjuvant radiotherapy, and general guidelines for managing keratinocyte carcinomas with perineural invasion. A better understanding of perineural invasion is essential to improve diagnosis, tailor interventions, and mitigate patient morbidity and mortality.

Intramedullary-Extramedullary Breast Metastasis to the Caudal Neuraxis Two Decades after Primary Diagnosis: Case Report and Review of the Literature.

BACKGROUND: Intramedullary metastases to the caudal neuraxis with exophytic extension to the extramedullary space are rare. We describe the unique case of a patient with locally recurrent breast cancer who developed an intramedullary-extramedullary metastasis to the conus medullaris and cauda equina 22 years after primary diagnosis, the longest interval between primary breast cancer and intramedullary spread to date. We also reviewed the published literature on focal breast metastases to the conus medullaris or cauda equina. CASE DESCRIPTION: A 66-year-old woman with a history of node-positive estrogen receptor/progesterone receptor-positive, infiltrating ductal carcinoma diagnosed in 1997 and locally recurrent in 2007. Initial treatment included lumpectomy and targeted chemoradiation with mastectomy and hormonal therapy at recurrence. Twelve years later, she developed 6 weeks of bilateral buttock and leg pain without motor or sphincter compromise. Magnetic resonance imaging of the total spine revealed a 2 x 1.7 cm bilobed intradural, intramedullary-extramedullary, homogenously enhancing, T1-and T2-isointense lesion involving the conus medullaris and cauda equina. She underwent subtotal resection of a hormone receptor-positive breast metastasis. Her pain improved postoperatively and she was stable at 5 months. CONCLUSIONS: We provide evidence that patients who present with symptoms of spinal neurologic disease and a history of hormone receptor-positive breast cancer require high suspicion for metastatic pathology, despite significant time lapse from primary diagnosis. The tumor may involve both the intramedullary and extramedullary space, complicating resection. Symptom relief and quality of life should guide resection of metastatic lesions to the caudal neuraxis.

Secondary Neurolymphomatosis of the Radial Nerve: A Diagnostic Challenge.

BACKGROUND Secondary neurolymphomatosis is a rare clinical condition that may be observed in patients with hematologic malignancies. Clinical findings can overlap with other conditions. Diagnosis can be obtained by magnetic resonance imaging (MRI) and imaging with positron emission tomography (PET) and confirmed by biopsy. CASE REPORT A 55-year-old male patient with known previous history of periocular non-Hodgkin's lymphoma mucosa-associated lymphoid tissue (MALT) type presented reporting he had a focal soft-tissue swelling mass on the external side of the right arm, suspected for lipoma. US, MRI, and FDG PET/CT were performed, revealing malignant imaging characteristics of the lesion, suspected to be a neurolymphoma. A biopsy confirmed the nature of the lesion. No further sites of malignancy were detected on whole-body PET/CT. CONCLUSIONS Lymphomatous involvement of peripheral nerves may clinically overlap with other, more common, benign conditions; therefore, although it is rarer, this diagnosis has to be considered in patients with a clinical history of hematologic malignancies.

Unilateral leg weakness and pain secondary to metastatic anal squamous cell carcinoma.

A 58-year-old man presented to colorectal clinic with intermittent rectal bleeding, weight loss, also pain and weakness affecting his lower back and right leg. On inspection, there were perianal warts (condyloma acuminata), with an additional palpable anal lesion on digital rectal examination, confirmed by colonoscopy. Subsequent imaging revealed a large right psoas abscess, and an associated paravertebral soft tissue component invading the right lumbosacral plexus and nerve roots at L4, L5 and S1. Biopsy of the paravertebral mass revealed metastatic squamous cell carcinoma. Given his symptomatology, and also as biopsy of the perianal warts revealed high-grade squamous intraepithelial lesion/grade III anal intraepithelial neoplasia on histology with infection by human papillomavirus type 6, the primary was presumed to be anal. This was a case of sciatic pain which proved to be diagnostically challenging on initial presentation to primary care. This mode of presentation and pattern of metastasis are uncommon in anal cancer.

Multiple secondary cauda equina non-Hodgkin's lymphoma: a case report and literature review.

BACKGROUND: Secondary central nervous system involvement of non-Hodgkin's lymphoma (NHL) is rare and with poor prognosis, the most common pathological type is diffuse large B cell lymphoma (DLBCL). Although it can occur in any part of central nervous system, it rarely directly infiltrates the spinal cord or cauda equina. CASE PRESENTATION: We present the case of 64-year-old immunocompetent man with a worsening pain of waist and left lower extremity, accompanied by numbness and paresis of bilateral lower extremity for 20 days. His previous medical history included a resection of painless mass in the left groin in another hospital 7 months ago, and the pathological diagnosis was non-Hodgkin small B cell lymphoma. Gd-enhanced MRI and F-18 FDG PET-CT scan demonstrated multiple infiltrations in the cauda equina. During the operation, we removed as many as 11 subdural-extramedullary bean-size lesions involving multiple nerve roots. The paralysis of his left leg recovered rapidly after the operation. During the follow-up period of more than one year, he underwent standard R-CHOP chemical therapy, no evidence of recurrence was noted until the 13th month, the patient died because of intracranial relapse. CONCLUSIONS: Imaging examination is important in the diagnosis of multiple secondary cauda equina non-Hodgkin's lymphoma, and we highlight the significance of gadolinium-enhanced MRI and F-18 FDG-PET/CT in preoperative diagnosis as well as the previous history.

A DSTYK mutation activates ERK1/2 signaling to promote intraspinal dissemination in a case of solitary fibrous tumor/hemangiopericytoma.

Intracranial solitary fibrous tumors/hemangiopericytomas (SFT/HPCs) are vascular tumors that have a high rate of local recurrence and extracranial metastases. Intradural extramedullary spinal dissemination of intracranial SFT/HPC is extremely rare. There is a paucity of data available to elucidate the molecular mechanisms of intraspinal dissemination of intracranial SFT/HPC. Herein, we presented a case of intracranial SFT/HPC with intraspinal metastasis. The resected tumor specimens were enrolled in a clinical sequencing program, including whole-exome and transcriptome sequencing. By comparing genomic sequencing data of the intracranial tumors with intraspinal metastasis, we established the somatic mutational profiles of these tumors. Clonality analysis revealed a distinct subclonal structure in the intracranial tumor and its intraspinal metastasis, which might reflect the possibility of intratumoral clonal selection and evolution during the process of tumor dissemination. Through bioinformatics analysis and Sanger sequencing validation, a DSTYK mutation (Met296Ile) was identified as a candidate driver of intraspinal metastasis in this SFT/HPC case. Further, an intracranial tumor-derived SFT/HPC cell line, HPC3, was established to explore the mechanisms of the DSTYK mutation in promoting SFT/HPC metastasis. Based on the HPC3 cell model, we found that the DSTYK mutation promoted cell migration and invasion of HPC3 cells via activation of ERK1/2 signaling, which was inhibited by the MEK/ERK inhibitor AZD6244. The DSTYK mutation was also shown to upregulate the expression of two metastasis-related molecules: MMP2 and MMP9 in HPC3 cells; however, this effect was attenuated by AZD6244 treatment. Therefore, the DSTYK mutation may activate ERK1/2/MMP2/9 signaling to promote tumor cell metastasis in SFT/HPC. In conclusion, our study revealed the potential role of DSTYK mutation in the regulation of intraspinal metastasis of SFT/HPC, which might provide new biological insights into this rare disease.

68Ga-PSMA Uptake in Prostate Cancer Sciatic Nerve Metastasis.

Most prostate cancers spread to regional lymph nodes, axial skeleton and lungs. Perineural malignant involvement is very rare. We present a Ga-PSMA PET/CT image of a sciatic nerve metastasis in a 65-year-old man with recurrent prostate cancer.

Multimodal Imaging Aids in the Diagnosis of Perineural Spread of Prostate Cancer.

BACKGROUND: The perineural spread of prostate cancer into pelvic peripheral nerves is a rare, but increasingly recognized, entity. This form of metastasis invades the lumbosacral plexus via the splanchnic nerves innervating the prostate. The prevalence of perineural spread is likely underappreciated, and further imaging-based studies are needed to elucidate its true frequency. METHODS: A retrospective review was performed using an institutional radiology database. Medical reports from patients with prostate cancer who had undergone positron emission tomography (PET) imaging were queried for terms suggestive of perineural spread. PET and magnetic resonance imaging (MRI) from the identified patients were blindly reviewed for peripheral nerve involvement by 2 nuclear medicine and 2 musculoskeletal radiologists. RESULTS: A total of 22 patients were identified. After review by the radiologists, 16 patients had positive findings of perineural spread found on PET and 15 had abnormalities found on MRI involving lumbosacral plexus neural elements. All patients with biopsy-proven neoplastic perineural spread (including 1 patient with malignant peripheral nerve sheath tumor) had positive findings on both PET and MRI. All patients with biopsy-proven inflammatory lesions had negative PET and variable MRI findings. CONCLUSIONS: The perineural spread of prostate cancer might be more common than previously thought. The use of multimodal imaging for patients suspected of having perineural spread should be a part of the treatment algorithm. Targeted fascicular biopsy might be indicated for patients with progressive neurological deficit and an unclear diagnosis.

Lung Adenocarcinoma Metastasis Mimicking Peripheral Nerve Sheath Tumor: Case Report and Review of Literature.

Root metastases of solid organ carcinomas are rare entities. Because of their rare occurrence, they can be confused with nerve sheath tumors, such as schwannomas or neurofibromas, when detected by magnetic resonance imaging. In this paper, we reported a case of a 72-year-old woman with S1 root metastasis originating from lung adenocarcinoma. In addition, we reviewed the literature and presented the diagnosis and treatment stages of this pathology. Surgical resection should be the main treatment for symptomatic metastases. Gross total resection of tumors is usually not possible with preservation of neurologic functions. Nerve root decompression, subtotal resection, and adjuvant treatments seem to represent the best treatment option for these patients.

Metastatic Complications of Cancer Involving the Central and Peripheral Nervous Systems.

Neurologic complications of cancer may involve both the central nervous system and peripheral nervous system manifesting as brain, leptomeningeal, intramedullary, intradural, epidural, plexus, and skull base metastases. Excluding brain involvement, neurologic complications affecting these other sites are relatively infrequent, but collectively they affect more than 25% of patients with metastatic cancer causing significant morbidity and mortality. Early diagnosis and intervention optimize quality of life and improve survival.

Plexus and peripheral nerve metastasis.

Cancer in the form of solid tumors, leukemia, and lymphoma can infiltrate and metastasize to the peripheral nervous system, including the cranial nerves, nerve roots, cervical, brachial and lumbosacral plexuses, and, rarely, the peripheral nerves. This review discusses the presentation, diagnostic evaluation, and treatment options for metastatic lesions to these components of the peripheral nervous system and is organized based on the anatomic distribution. As skull base metastases (also discussed in Chapter 14) result in cranial neuropathies, these will be covered in detail, as well as cancers that directly infiltrate the cranial nerves. Particular emphasis is placed on the clinical, imaging, and electrodiagnostic features that differentiate neoplastic plexopathies from radiation-induced plexopathies. Neurolymphomatosis, in which malignant lymphocytes invade the cranial nerves, nerve roots, brachial and lumbosacral plexuses, and peripheral nerves, is a rare manifestation of lymphoma and leukemia. Diagnoses of neurolymphomatosis are often missed or delayed given its varied presentations, resulting in poorer outcomes. Thus this disease will also be discussed in depth.

Perineural Spread of Melanoma to the Brachial Plexus: Identifying the Anatomic Pathway(s).

BACKGROUND: Perineural spread of melanoma is a well-known mechanism of metastasis in cases involving cranial nerves. Brachial plexus involvement is rare, and the pathway is unknown. METHODS: A retrospective review of the Mayo Clinic database was performed to identify patients with a history of melanoma and brachial plexus compromise treated between 1994 and 2017. Inclusion criteria were a history of melanoma, a clinical diagnosis of brachial plexopathy, radiologic features consistent with perineural spread, and biopsy of melanoma within nerves. RESULTS: We identified 42 patients (24 men and 18 women; median age, 61 years; range, 37-84 years) with a history of melanoma and brachial plexopathy. On a review of clinical information, 2 cases met our inclusion criteria. Both patients presented with progressive brachial plexopathy, and imaging studies revealed features consistent with perineural spread. In 40 excluded patients, brachial plexopathy was caused by metastasis to axillary lymph nodes (n = 11), trauma (n = 8), post-surgical sequelae (n = 7), tumors other than melanoma (n = 5), inflammation (n = 5), radiation (n = 2), a combination of radiation and postsurgical changes (n = 1), and radiculopathy (n = 1). CONCLUSIONS: The 2 patients identified had similar clinical and radiologic features. We believe that there is a pattern of perineural spread to the brachial plexus through the cervical plexus. A literature review identified several recently published cases demonstrating an analogous mechanism of melanoma spread involving upper cervical nerves, supporting our proposed pathway.

Targeted fascicular biopsy in a patient with prostate cancer.

Patients who present with a history of cancer and the new onset of lumbosacral or peripheral neuropathy should be evaluated for the potential of metastasis. Targeted fascicular biopsy can be useful to diagnose atypical lesions within peripheral nerves in patients with major or progressive neurological deficits. In this video, the authors demonstrate the technique of targeted fascicular biopsy of the sciatic nerve in a 63-year-old man with a history of prostate cancer. The video can be found here: https://youtu.be/PTOX9XxNBDU .

Review of periorbital nerve enlargement and biopsy techniques.

Periorbital nerve enlargement commonly indicates perineural invasion of malignancy or inflammatory conditions. This study reviews the role of supraorbital and infraorbital nerve biopsies in patients presenting with radiographic enlargement and to elucidate the surgical technique involved. A retrospective chart review (1997-2014) was performed at a single tertiary center. Patients with radiographic confirmation of enlarged supraorbital/infraorbital nerves that underwent biopsy were included. Charts were reviewed for: patient demographics and history, clinical symptoms and findings, radiographic findings, surgical method, and treatment. Five patients (4 female, 1 male) met inclusion criteria. Average age was 72.4 years (range 36-90). Four patients had history of cutaneous malignancy. All presented with diplopia and/or dysesthesias. Clinical examination confirmed decreased V1 and/or V2 sensation for 4 patients. Imaging revealed enlargement of V1, V2, and/or V3 in all patients. Infraorbital nerve biopsies were performed in 3 patients via transconjunctival fornix-based orbitotomy with subperiosteal dissection along orbital floor followed by unroofing of infraorbital canal. The remaining 2 underwent supraorbital nerve biopsy via sub-brow incision onto superior orbital rim with reflection of periosteum. Biopsies confirmed squamous cell carcinoma(3), mucoepidermoid carcinoma(1), and idiopathic orbital inflammation(1). Three patients initiated treatment in <1 month. One decided to follow-up closer to home, one was lost to follow-up. For patients presenting with enlarged supraorbital/infraorbital nerves, biopsy can rapidly confirm the underlying condition and facilitate early treatment. A sub-brow approach offers direct access to supraorbital nerve while transconjunctival fornix-based anterior orbitotomy with canal unroofing allows access to infraorbital nerve.

Metastatic squamous cell carcinoma to the superior cervical ganglion mimicking a retropharyngeal lymph node.

BACKGROUND: Metastasis of squamous cell carcinoma (SCC) to the superior cervical ganglion (SCG) has never been reported. Its anatomic location may easily be mistaken for a retropharyngeal lymph node. We present the first case of SCC metastasis to the SCG. METHODS: We report a case of a 69year-old never smoking male, who presented with right retropharyngeal PETCT-avid disease following chemoradiation for squamous cell carcinoma of the tonsil. He was brought to the operating room for resection, intraoperative radiation and reconstruction. RESULTS: Intraoperatively, visualization and frozen section confirmed squamous cell carcinoma located in the superior cervical ganglion. The ganglion was resected, intraoperative radiation was given and the patient was reconstructed with a radial forearm free flap. Postoperatively, the patient displayed features of a Horner's syndrome. CONCLUSIONS: The superior cervical ganglion may be mistaken for a retropharyngeal lymph node. Although extremely rare, these entities may be differentiated on the basis of radiological studies.

Diagnosis of secondary peripheral neurolymphomatosis: a multi-center experience.

Here, we describe our experience with secondary neurolymphomatosis (NL) in non-Hodgkin lymphoma patients, with the emphasis on the diagnosis process. A retrospective chart review of 12 patients from 3 tertiary academic centers between January 2005 and December 2015 was conducted. Secondary NL was diagnosed within a median interval of 10 months (range 5-41 months) after initial diagnosis of NHL. Painful neuropathy was present in 66.7%, but the diagnosis of NL was delayed in nine out of 12 patients (75.0%) by median of 2 months. Diagnostic modalities included CSF analysis performed in nine patients (75.0%), electrodiagnostic studies in seven (58.3%), radiologic studies in all, and nerve biopsy in two (16.7%). The diagnostic yield was 100.0% (15/15) for FDG-PET/CT and 75.0% (9/12) for MRI. Our experience emphasizes the importance of clinical suspicion of NL in patients with previous history of NHL and selection of diagnostic modality with the greatest clinical utility.

Inhibition of NF-kappa B pathway leads to deregulation of epithelial-mesenchymal transition and neural invasion in pancreatic cancer.

NF-κB has an essential role in the initiation and progression of pancreatic cancer and specifically mediates the induction of epithelial-mesenchymal transition and invasiveness. In this study, we demonstrate the importance of activated NF-κB signaling in EMT induction, lymphovascular metastasis, and neural invasion. Modulation of NF-κB activity was accomplished through the specific NF-κB inhibitor (BAY 11-7085), triptolide, and Minnelide treatment, as well as overexpression of IKBα repressor and IKK activator plasmids. In the classical lymphovascular metastatic cascade, inhibition of NF-κB decreased the expression of several EMT transcription factors (SNAI1, SNAI2, and ZEB1) and mesenchymal markers (VIM and CDH2) and decreased in vitro invasion, which was rescued by IKK activation. This was further demonstrated in vivo via BAY 11-7085 treatment in a orthotopic model of pancreatic cancer. In vivo NF-κB inhibition decreased tumor volume; decreased tumor EMT gene expression, while restoring cell-cell junctions; and decreasing overall metastasis. Furthermore, we demonstrate the importance of active NF-κB signaling in neural invasion. Triptolide treatment inhibits Nerve Growth Factor (NGF) mediated, neural-tumor co-culture in vitro invasion, and dorsal root ganglia (DRG) neural outgrowth through a disruption in tumor-neural cross talk. In vivo, Minnelide treatment decreased neurotrophin expression, nerve density, and sciatic nerve invasion. Taken together, this study demonstrates the importance of NF-κB signaling in the progression of pancreatic cancer through the modulation of EMT induction, lymphovascular invasion, and neural invasion.

Imaging of metastases from breast cancer to uncommon sites: a pictorial review.

There are three types of breast cancer recurrence which can occur after initial treatment: local, regional, and distant. Distant metastases are more frequent than local and regional recurrences. It usually occurs several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer. Although the common distant metastases are bone, lung and liver, breast cancer has the potential to metastasize to almost any region of the body. Early detection and treatment of distant metastases improves the prognosis, therefore radiologists and clinicians should recognize the possibility of metastasis from breast cancer and grasp the imaging characteristics. In this report, we demonstrate the imaging characteristics of metastases from breast cancer to uncommon sites.