Clinical Reasoning: An Unusual Etiology of Lumbosacral Plexopathy in a Patient With HIV.

We present a compelling case of uncontrolled diabetes, who initially presented as diabetic lumbosacral radiculoplexus neuropathy (DLRPN), with radicular pain in the right lower limb (LL) followed by asymmetric weakness of both LLs (right greater than left) with wasting in the medial compartment of the right thigh and significant sensory loss in the bilateral sural and right saphenous nerve distribution. Electrophysiology was suggestive of right lumbosacral radiculoplexus neuropathy. Incidentally, the patient tested positive for HIV-1 at our tertiary care center. CSF analysis revealed markedly elevated protein levels (>400 mg/dL) with lymphocytosis, a red flag for DLRPN. This observation led to further workup. Nerve biopsy showed large collections of perivascular endoneurial and epineurial lymphoid inflammatory cells, which favored an alternative diagnosis. This case highlights the intricate interplay between HIV infection, diabetes, and neurologic manifestations, challenging the initial clinical suspicion of DLRPN. This study emphasizes the importance of considering atypical presentations of neuropathy, especially in the context of coexisting medical conditions, and emphasizes the significance of comprehensive diagnostic workup, including CSF studies and nerve biopsy, for an accurate diagnosis.

Clinical Reasoning: A 61-Year-Old Man With Progressive Right Leg Numbness and Weakness.

Approaching patients with lumbosacral plexopathies or radiculoplexus neuropathies can be challenging and a well-defined strategy considering specific etiologies is necessary to arrive at the correct diagnosis. In this case, a 61-year-old man presented with a 10-year history of slowly progressive right lower extremity numbness and weakness. His examination was marked by right lower extremity weakness, decreased temperature/pinprick and proprioceptive/vibratory sensations, hypotonia, muscle atrophy, and absent right patellar, and ankle deep tendon reflexes. His workup was notable for electrodiagnostic findings of chronic lumbosacral radiculoplexus neuropathy and neuroimaging revealing marked enlargement, T2 signal abnormality, and faint contrast enhancement in multiple nerves. A targeted fascicular nerve biopsy yielded the final diagnosis of a rare disease. This case highlights the differential diagnoses of lumbosacral plexopathies or radiculoplexus neuropathies, including a guided workup. We also discuss the typical features of a rare diagnosis and its therapeutic options.

Radiation-induced lumbosacral plexopathy and pelvic insufficiency fracture: A case report of unique coexistence of complications after radiotherapy for prostate cancer.

Case reports of plexopathy after prostate cancer are usually neoplastic. Radiation-induced lumbosacral plexopathy and insufficiency fractures have clinical significance due to the need to differentiate them from tumoral invasions, metastases, and spinal pathologies. Certain nuances, including clinical presentation and screening methods, help distinguish radiation-induced plexopathy from tumoral plexopathy. This case report highlights the coexistence of these two rare clinical conditions. Herein, we present a 78-year-old male with a history of radiotherapy for prostate cancer who developed right foot drop, severe lower back and right groin pain, difficulty in standing up and walking, and tingling in both legs over the past month during remission. The diagnosis of lumbosacral plexopathy and pelvic insufficiency fracture was made based on magnetic resonance imaging, positron emission tomography, and electroneuromyography. The patient received conservative symptomatic treatment and was discharged with the use of a cane for mobility. Radiation-induced lumbosacral plexopathy following prostate cancer should be kept in mind in patients with neurological disorders of the lower limbs. Pelvic insufficiency fracture should also be considered if the pain does not correspond to the clinical findings of plexopathy. These two pathologies, which can be challenging to diagnose, may require surgical or complex management approaches. However, in this patient, conservative therapies led to an improvement in quality of life and a reduction in the burden of illness.

Bruns Garland Syndrome as the first presentation of type 2 diabetes: two case reports and a practical approach to diagnosis.

BACKGROUND: Diabetes is a global health problem causing a significant burden on the healthcare systems both due to the disease itself and associated complications. Diabetic radiculoplexus neuropathies or Bruns-Garland syndrome constitutes a rare form of microvascular complications, more commonly affecting the lumbosacral plexus and, very rarely, the cervical plexus. We describe two Sri Lankan males who presented with diabetic lumbosacral radiculoplexus neuropathy and diabetic cervical radiculoplexus neuropathy as the initial manifestation of diabetes. CASE DESCRIPTION: Case 1: a 49-year-old Sri Lankan hotel chef presented with subacute painful weakness and wasting of the left upper arm for 3 months and weight loss. Left upper limb proximal muscles were wasted with diminished power and reflexes. A nerve conduction study showed comparative amplitude reduction. An electromyogram revealed positive sharp waves, frequent fibrillations, and high amplitude polyphasic motor unit potentials with reduced recruitment in proximal muscles of left upper limb. Case-2: a 47-year-old Sri Lankan carpenter presented with subacute progressive asymmetrical painful weakness and wasting of bilateral thighs for 5 months and weight loss. Lower limb proximal muscles were wasted with reduced power and knee jerks. The nerve conduction study was normal. The electromyogram was similar to case 1 involving both quadratus femoris muscles, which was more prominent on the left side. The work up for an underlying etiology revealed only elevated fasting blood glucose and HbA1c, suggesting a new diagnosis of diabetes associated with neurological symptoms. Patient 1 was diagnosed with diabetic cervical radiculoplexus neuropathy and patient 2 with diabetic lumbosacral radiculoplexus neuropathy. Both showed significant improvement following optimization of glycemic control together with symptomatic treatment and physiotherapy. CONCLUSION: Diagnosis of diabetic radiculoplexus neuropathy requires a comprehensive workup to rule out other sinister pathologies. This case report has a dual importance; it describes diabetic radiculoplexus neuropathy as the very first manifestation of two previously healthy people, giving rise to a new diagnosis of diabetes and, at the same time, reporting on diabetic cervical radiculoplexus neuropathy, which is extremely rare and has never been previously reported in Sri Lanka.

Minimally Invasive Approaches for Lumbosacral Plexus Schwannomas.

BACKGROUND AND OBJECTIVES: Lumbosacral plexus schwannomas (LSPSs) are benign, slow-growing tumors that arise from the myelin sheath of the lumbar or sacral plexus nerves. Surgery is the treatment of choice for symptomatic LSPSs. Conventional retroperitoneal or transabdominal approaches provide wide exposure of the lesion but are often associated with complications in the abdominal wall, lumbar or sacral plexus, ureter, and intraperitoneal organs. Advances in technology and minimally invasive (MIS) techniques have provided alternative approaches with reliable efficacy compared with traditional open surgery. We describe 3 MIS approaches using tubular retractor systems according to the lesion level. METHODS: This was a multicenter, retrospective observational cohort study to evaluate the use of MIS tubular approaches for surgical resection of LSPSs. We included 23 lumbar and upper sacral plexus schwannomas. Clinical presentation, spinal level, surgical duration, degree of resection, days of hospitalization, pathological anatomy of the tumor, approach-related surgical difficulties, and outcomes were collected. RESULTS: The posterior oblique approach was used in 43.5% of the cases, the transpsoas approach in 39.1%, and the transiliac in 17.4%. The mean operative time was 3.3 hours, and the mean hospitalization was 2.5 days. All tumors were WHO grade 1 schwannoma. Postoperative MRI confirms gross total resection in 91.3% of the patients. No patient requires instrumentation. The pros and cons of each approach were summarized. CONCLUSION: The MIS approaches adapted to the lumbar level may improve surgeons' comfort allowing a safe resection of retroperitoneal LSPS.

Uterine Fibroid-Induced Compressive Neuropathy of Lumbar Plexus and Obturator Nerve.

Introduction: Uterine fibroids are the most common gynecologic tumors in reproductive-aged women with a prevalence of up to 80%. Symptoms can range from heavy vaginal bleeding and bulk symptoms to, less frequently, deep vein thrombosis and bowel obstruction. Case Description: A 32-year-old female patient presented with acute-onset of right groin and knee pain, and difficulty ambulating. A large posterior uterine fibroid was found to be compressing branches of the lumbar plexus, including the obturator nerve. The patient underwent gynecologic evaluation and an urgent laparoscopic myomectomy. Postoperatively, she had significant improvement in neurologic symptoms. She continued physical therapy for residual mild paresthesia and pain with prolonged ambulation. Discussion: Large pelvic masses such as uterine fibroids should be considered on the differential diagnosis for acute-onset non-gynecologic symptoms such as compressive neuropathy, which require urgent evaluation and possible surgical management.

Surgical and oncologic outcomes in dogs with malignant peripheral nerve sheath tumours arising from the brachial or lumbosacral plexus.

Malignant peripheral nerve sheath tumours (MPNST) of a plexus nerve or nerve root cause significant morbidity and present a treatment challenge. The surgical approach can be complex and information is lacking on outcomes. The objective of this study was to describe surgical complication rates and oncologic outcomes for canine MPNST of the brachial or lumbosacral plexus. Dogs treated for a naïve MPNST with amputation/hemipelvectomy with or without a laminectomy were retrospectively analysed. Oncologic outcomes were disease free interval (DFI), overall survival (OS), and 1- and 2-year survival rates. Thirty dogs were included. The surgery performed was amputation alone in 17 cases (57%), and amputation/hemipelvectomy with laminectomy in 13 cases (43%). Four dogs (13%) had an intraoperative complication, while 11 dogs (37%) had postoperative complications. Histologic margins were reported as R0 in 12 dogs (40%), R1 in 12 dogs (40%), and R2 in five dogs (17%). No association was found between histologic grade and margin nor extent of surgical approach and margin. Thirteen dogs (46%) had recurrence. The median DFI was 511 days (95% CI: 140-882 days). The median disease specific OST was 570 days (95% CI: 467-673 days) with 1- and 2-year survival rates of 82% and 22% respectively. No variables were significantly associated with recurrence, DFI, or disease specific OST. These data show surgical treatment of plexus MPNST was associated with a high intra- and postoperative complication rate but relatively good disease outcomes. This information can guide clinicians in surgical risk management and owner communication regarding realistic outcomes and complications.

Lumbosacral Radiculoplexus Neuropathy After COVID-19.

INTRODUCTION: Lumbosacral Radiculoplexus Neuropathy (LRPN) is a subacute, painful, paralytic, asymmetric immune-mediated lower-limb neuropathy associated with weight loss and diabetes mellitus (called DLRPN). Approximately one-third of LRPN cases have a trigger. Our purpose is to show that COVID-19 can trigger LRPN. CASE REPORT: We describe the clinical, neurophysiological, radiologic, and pathologic findings of a 55-year-old man who developed DLRPN after severe acute respiratory syndrome coronavirus-2 infection. Shortly after mild coronavirus disease 2019 (COVID-19), the patient developed severe neuropathic pain (allodynia), postural orthostasis, fatigue, weight loss, and weakness of bilateral lower extremities requiring wheelchair assistance. One month after COVID-19, he was diagnosed with type 2 diabetes mellitus. Neurological examination showed bilateral severe proximal and distal lower extremity weakness, absent tendon reflexes, and pan-modality sensation loss. Electrophysiology demonstrated an asymmetric axonal lumbosacral and thoracic radiculoplexus neuropathies. Magnetic resonance imaging showed enlargement and T2 hyperintensity of the lumbosacral plexus. Cerebral spinal fluid (CSF) showed an elevated protein (138 mg/dL). Right sural nerve biopsy was diagnostic of nerve microvasculitis. He was diagnosed with DLRPN and treated with intravenous methylprednisolone 1 g weekly for 12 weeks. The patient had marked improvement in pain, weakness, and lightheadedness and at the 3-month follow-up was walking unassisted. CONCLUSION: COVID-19 can trigger postinfectious inflammatory neuropathies including LRPN.

Surgical Management of Lumbosacral Plexus Tumors.

BACKGROUND: Lumbosacral plexus tumors are uncommon, and because of their deep location and proximity to critical nerves subserving lower extremity function, understanding surgical approaches and short-term outcomes is important. METHODS: In a retrospective case series of lumbosacral plexus tumor surgeries performed from May 2000 to July 2021 by a single neurosurgeon, demographic information, clinical presentation, imaging studies, and operative outcomes were analyzed. RESULTS: A total of 42 patients with mean age of 48.3 years (range, 16-84 years) underwent surgery for a lumbosacral plexus tumor. Patients presented with leg pain (n = 25; 59.5%), followed by back/flank pain (n = 5; 11.9%), abdominal/pelvic pain (n = 5; 11.9%), leg weakness (n = 5; 11.9%), and leg numbness (n = 3; 7.1%). The most common tumor pathology was schwannoma (n = 20; 50.0%) followed by neurofibroma (n = 9; 22.5%). A retroperitoneal approach was used in all cases. Gross total resection was achieved in 23 (54.8%) patients, and only 1 (2.4%) patient exhibited symptomatic tumor recurrence after subtotal resection of a malignant tumor. Mean follow-up was 33.1 months (range, 1-96 months). Postoperatively, patient neurological status remained unchanged or improved (n = 37; 88.1%). Complications were infrequent, with 4 (9.5%) patients experiencing new sensory symptoms and 1 patient (2.4%) experiencing new anticipated motor weakness after en bloc resection of a malignant tumor. CONCLUSIONS: Indications for surgery include pain and/or neurological symptoms attributable to the lesion or large size if asymptomatic. Careful study of preoperative imaging is necessary to determine the best approach. Intraoperative nerve stimulation is essential to preserve function and guide extent of resection in benign tumors.

Lumbosacral plexopathy secondary to discectomy and fixation.

Lumbosacral plexopathy (LSP) is a rare entity characterized by acute onset of pain followed by sensory and motor deficits, reflex changes and muscle atrophy. The diagnosis is based on clinical and EMG findings. LSP can result from pelvic tumors, infections, trauma, abdominopelvic or spinal surgery, radiation, intravenous drug abuse, diabetic neuropathy, vasculitis or maybe idiopathic. We present a case report of LSP following spinal surgery treated by pulse steroid and immunotherapy.

Case report: radiation-induced lumbosacral plexopathy - a very late complication of radiotherapy for cervical cancer.

BACKGROUND: Lumbosacral plexopathy caused by radiotherapy is a rare but severe consequence of cancer treatment. This condition often leads to varying degrees of sensory and motor impairment. Neurological complications, which are typically permanent, manifest a long period after irradiation. CASE PRESENTATION: We describe a case of progressive lower extremity weakness and sensory impairment in a woman who had been effectively treated with radiotherapy for cervical cancer with development 36 years after irradiation. The electrophysiological assessment revealed a subacute bilateral axonal lesion of the lumbosacral plexus. None of the clinical manifestations, serology, cerebrospinal fluid or imaging data discovered an explanation other than radiation-induced lumbosacral plexopathy (RILP). CONCLUSIONS: This case demonstrates that RILP may emerge more than 30 years after the radiotherapy.

Lumbosacral Plexus Neurolymphomatosis: A Typical 18FDG PET/CT Pattern to Recognize.

ABSTRACT: A 79-year-old man anteriorly treated for primary central nervous system diffuse large B-cell lymphoma with MRI complete response after immunochemotherapy was referred 1 year later for 18FDG PET/CT because of right persistent lombosciatic radicular pain for 6 months with negative medullary and spine MRI and negative cerebrospinal fluid cytology. Linearly intense uptake was observed in several roots of lumbosacral plexus, highly suggestive of peripheral neurolymphomatosis relapse. No specific treatment was engaged because of rapid decrease of performance status leading to death.

A case report of secondary neurolymphomatosis showing selective nerve infiltration and massive lumbar plexus enlargement.

BACKGROUND: Neurolymphomatosis (NL) is a rare manifestation of malignant lymphoma that shows selective infiltration to the peripheral nervous system primarily or secondarily. We report a patient with secondary NL caused by germinal center B-cell (GCB)-type diffuse large B-cell lymphoma (DLBCL) who showed selective infiltration of the lumbar plexus to the spinal cord and massive nerve enlargement resulting in severe pain. CASE PRESENTATION: A 72-year-old female exhibited asymmetric motor and sensory impairments and pain in the lower limbs that progressed for five months. Magnetic resonance imaging (MRI) showed an enlarged lumbar plexus, which continued to the cauda equina via the L3 and L4 spinal nerves. Her symptoms gradually worsened. Ten months after the onset of symptoms, the enlarged cauda equina filled the spinal canal space, and the spinal cord was swollen. A cauda equina biopsy was performed, and she was diagnosed with GCB-type DLBCL with CD10 positivity. The primary tumor was found in a mammary cyst. The autopsy study did not show apparent infiltration, except in the nervous system. CONCLUSIONS: Although there are many neurologic phenotypes of malignant lymphoma, the association between the cytological characteristics of lymphoma and the neurological phenotypes is still unclear. Several reports of CD10-positive secondary NL are available, whereas peripheral or central nervous tissue origin lymphoma cases are mostly negative for CD10. CD10 staining may be useful for distinguishing primary NL from secondary NL. NL often has a strong organotropism for peripheral nervous tissue, which makes early diagnosis challenging.

Excision of deep endometriosis nodules of the parametrium and sacral roots in 10 steps.

OBJECTIVE: To present 10 consecutive, standardized, and reproducible surgical steps allowing complete excision of deep endometriosis nodules infiltrating the parametrium and sacral roots. DESIGN: Surgical video presenting the 10 surgical steps. Local institutional review board approval was not required for this video article, because the video describes a technique and the patient cannot be identified whatsoever. SETTING: Endometriosis Center. PATIENTS: Patients undergoing excision of deep endometriosis nodules of the parametrium and sacral roots. INTERVENTION: The excision of deep endometriosis infiltrating the parametrium down to the sacral roots may be performed following 10 steps: complete ureterolysis and removal of ureteral stenosis; opening of the pararectal space in contact with the rectum in a sagittal plane; dissection caudally toward the rectovaginal space, section of the rectovaginal nodule in two separate blocks infiltrating the rectum and vagina, respectively, all the way down to the levator ani muscles; dissection of the presacral space and identification of the superior hypogastric plexus and hypogastric nerve; transverse incision of the peritoneum at the level of the promotorium, extended laterally above the origin of the hypogastric vessels; anterograde dissection of the hypogastric artery and identification of the hypogastric vein; anterograde dissection of the hypogastric vein and opening of Okabayashi space, followed by identification and, when required, ligation of hypogastric vein tributaries; dissection is extended behind the venous network with identification of the pyriform muscles and sacral roots S2, S3, and S4; anterograde dissection of the nerve network and inferior hypogastric plexus, up to the posterior limits of the deep endometriosis nodule; and excision of the deep endometriosis nodule from the posterior limit to the inferior limit in contact with the sacral roots, which should be released or shaved, then to the lateral limit in contact with the pyriform muscle and lateral pelvic wall. Additional steps may be required to remove adjacent infiltration of the vagina, rectum, bladder, or ureters. The movie does not reflect a similar approach in cases of isolated nodules of the sciatic nerves involving a specific lateral dissection plane between the external iliac vessels and the iliopsoas muscle. MAIN OUTCOME MEASURES: Description of 10 successive surgical steps. RESULTS: The 10-step procedure already has been employed in 70 women with deep endometriosis of the parametria involving sacral roots, in whom sensory or motor complaints were not completely relieved by continuous amenorrhea provided by contraceptive pill intake or gonadotropin-releasing hormone analogs. Baseline complaints included somatic pain (85.7%), severe bladder dysfunction (10%), or hydronephrosis (24.3%). Main localizations concerned sacral roots (95.7%), sciatic nerves (7.1%), mid/low rectum (87.1%), and bladder (21.4%). Operative time was 224 ± 94 minutes. Among postoperative complications, we recorded rectovaginal fistulae (14.3%), urinary tract fistulae (4.3%), and bladder dysfunction at 3 weeks (22.9%) and 12 months (5.7%) after the surgery. CONCLUSIONS: Laparoscopic excision of deep endometriosis nodules of the parametria involving the sacral roots is a challenging procedure, requiring good anatomic and surgical skills. Teaching such a complex procedure is a delicate task. By following 10 sequential steps, the surgeon may reduce the risk of hemorrhage originating from the hypogastric venous network, preserve as much as possible autonomic nerves and organ function, and successfully excise deep endometriosis nodules. However, transection of the internal iliac artery and vein should not be systematic, as it may adversely affect the vascular supply of the pelvis. Transection of small pelvic splanchnic nerves should be performed only if they actually are included in fibrous nodules, as it may be followed by sexual, bladder, and rectal dysfunction or perineal sensory effects. Although the 10 steps attempt to standardize the surgical approach in a challenging localization of deep endometriosis, they are not mandatory and their use should be individualized.

Pelvic Neuroanatomy: An Overview of Commonly Encountered Pelvic Nerves in Gynecologic Surgery.

OBJECTIVE: This video tutorial identifies key anatomic landmarks useful in identifying the path of the most commonly encountered pelvic nerves in benign gynecologic surgery. DESIGN: This is a narrated overview of commonly encountered pelvic nerves during benign gynecology, their origin, sensory, and motor function, as well as sequelae related to injury. SETTING: The unintended injury of pelvic neural connections can be a complication of any pelvic surgery, however, surgery for malignancy or endometriosis may increase the likelihood of encountering these nerves. The majority of focus surrounding surgical nerve injury, however, relates to patient positioning [1]. Injury to the pelvic nerves can lead to lifelong sexual, bladder, and defecatory dysfunction [2]. INTERVENTIONS: We review the Genitofemoral, Lateral Femoral Cutaneous, Ilioinguinal, Obturator, Superior and Inferior Hypogastric nerves, Pelvic Splanchnic nerves, and the Sacral nerves. Surgical illustrations are used (Fig. 1) alongside real-time narrated video to help viewers recognize the normal course of commonly encountered pelvic nerves at the time of gynecologic surgery (Figs2-3). CONCLUSION: The surgical management of complex pelvic disease can unfortunately carry significant patient morbidity [3]. The neural pathways traveling through the pelvis via the hypogastric nerves are responsible for proprioception, vaginal lubrication, and proper functioning or the urethral and anal sphincters [4]. Sparing these nerves during pelvic surgery, and especially when anatomic planes are distorted by pelvic disease, requires surgical expertise and an immense understanding of pelvic neuroanatomy [4,5]. Preservation of the pelvic neural pathways is necessary to deliver the best patient outcomes while minimizing unwanted surgical complications. This video tutorial also highlights the origin of these nerves, their anatomic location, procedures in which these nerves may be encountered, and what sequelae occur from their unintended injury.

Perineural Spread of Clear Cell Adenocarcinoma of Müllerian Origin Resulting in Neoplastic Lumbosacral Plexopathy.

BACKGROUND: Adenocarcinomas of müllerian origin are malignancies derived from tissues of the proximal third of the vagina, cervix, uterus, and fallopian tubes. These organs develop from the embryologic müllerian ducts. While reports of perineural spread of certain uterine and cervical carcinomas exist in the literature, to our knowledge, no reports of clear cell-type müllerian adenocarcinoma presenting with neural invasion of the lumbosacral plexus exist in the literature. CASE DESCRIPTION: A 77-year-old woman with a remote history of hysterectomy and bilateral salpingo-oopherectomy for benign disease presented for evaluation of foot drop. We present clinical, electromyographic, and imaging findings of her condition, which revealed a diffuse intraneural lesion of the ipsilateral lumbosacral plexus. Percutaneous biopsy of the lesion confirmed nerve infiltrating clear cell adenocarcinoma of müllerian origin. CONCLUSIONS: We present the first case of adenocarcinoma of müllerian origin with confirmed perineural spread presenting with ipsilateral lower extremity weakness. This case illustrates the importance of recognizing potential perineural spread of gynecologic malignancies to avoid delay in treatment.

Neurolymphomatosis of the lumbosacral plexus and its branches: case series and literature review.

BACKGROUND: Neurolymphomatosis (NL) is a direct process of invasion of peripheral nerves by lymphoma. It occurs in roughly 5% of patients with lymphoma and represents a particularly difficult diagnostic dilemma when it is the presenting focal manifestation of occult lymphoma. CASE PRESENTATION: We present 3 examples of invasion of the lumbosacral plexus and its branches. These cases demonstrate a protean clinical picture with regards to the time relationship to the clinical course of lymphoma and the neuroanatomical extent of lumbosacral plexus invasion. We demonstrate the complementary role of different imaging modalities. A review of the literature summarizes 23 reports where lumbosacral plexus invasion was the index manifestation, at the time of first diagnosis or recurrence of lymphoma. This series confirms the strong preponderance of B-cell type (92%). There is a marked predilection for involvement of the sciatic nerve (74%), either focally or in a longitudinally extensive fashion, from the ischium to the popliteal fossa. There can also be restricted and discrete involvement of tibial and fibular branches. In recent years, ultrasound and CT have been given a more limited role, as screening tools or as a guide for biopsy. MRI neurography and PET-CT have become leading diagnostic modalities for diagnosis, staging and assessment of treatment response. CONCLUSION: The diagnosis of NL may be challenging, and it was once only reached at autopsy. Improved diagnostic imaging of focal or even asymptomatic disease offers new hope for earlier diagnosis and successful targeted therapy.