Spinner, Robert J.

AbstractBackgroundLipomatosis of nerve (LN) is a complex peripheral nerve disorder characterized by fibrofatty nerve enlargement. MRI of this pathology is pathognomonic and obviates a diagnostic biopsy. Mutation in PIK3CA has been associated with LN cases with nerve‐territory overgrowth which may occur in some cases. We evaluate an association of LN of the sciatic nerve and early‐onset colonic diverticular disease and discuss the potential pathogenesis.MethodsOur institutional database was searched for LN cases. Available information of identified cases was reviewed, and cases with a confirmed diagnosis of LN affecting the lumbosacral plexus and/or sciatic nerve; available MRI of the affected nerve(s); and diverticular disease occurring in the area supplied by the nerve(s) affected by LN were further analyzed. PIK3CA mutation testing was performed on available tissue samples.ResultsWe identified 10 LN cases of lumbosacral plexus and/or sciatic nerve. Of these, three fulfilled our inclusion criteria. All three patients had concomitant colonic diverticular disease, diagnosed at a relatively young age. MRI studies of these cases showed LN involvement of the sacral nerves innervating the sigmoid colon. All three also had abnormal diagnostic workup including various GI tests and evidence of associated nerve‐territory overgrowth. Colonic tissue samples for PIK3CA mutation were negative.ConclusionWhile the pathogenesis of the colonic diverticular disease is increasingly recognized as being multifactorial, our observations are consistent with the potential role of autonomic nervous system dysfunction affecting either the pelvic floor musculature, or the colon itself (or both) in a subset of patients with early‐onset diverticular disease.

We report a patient who has been on tacrolimus for bilateral lung transplantation and presented with a brachial plexus injury (BPI), with unusual improvement of lower trunk innervated hand function. The lower trunk injury with resultant left hand paralysis had developed after his sternotomy 18 months ago. He has been treated with tacrolimus as part of his immunosuppression protocol since the surgery, without severe side effects. Physical examination at 18 months demonstrated unusual excellent grip pattern and full opposition of his thumb with slight claw deformity of his ulnar two digits. While the neurotoxic effects of tacrolimus are more emphasised, the neuroregenerative properties have been recently explored. The recovery in this patient is unique and unusual after BPI and is most likely as a result of the low dose tacrolimus treatment.

Malignant nerve sheath tumors involving cranial nerves are rare. We identified 13 cases of MCNST arising in cranial nerve or from benign nerve sheath tumors, all but three being intracranial. The patients included 10 males and 3 females, one pediatric (5 years) and the remainder ranging in age from 23 to 69 years (mean, 40). The vestibular (n=5) and vagal nerves (n=3) were favored sites, followed by posterior fossa (n=2), facial nerve (n=1), frontal lobe parenchyma (n=1) and the lateral ventricle (n=1). Some patients were known to have NF1(n=3) or probable NF2 (n=1). Three tumors arose in transition from a conventional schwannoma and one from a plexiform neurofibroma. The majority of the tumors (n=11) were high grade (5 WHO III and 6 WHO IV) lesions. Immunohistochemistry was performed in 11 cases; S‐100 protein reactivity was diffuse (n=1), partial (n=2), focal (n=5) or negative (n=3). Collagen IV was also diffuse (n=2), partial (n=3), focal (n=5) or negative (n=1). p53 protein staining was high (n=7), moderate (n=2), or low (n=2). Clinical follow‐up was available in 10 cases; of the 8 patients who died, six patients did so within six months of surgery, and two within three years. Only one tumor, a grade IV MCNST with heterologous bone formation, developed extensive spinal leptomeningeal drop metastases. The one pediatric patient is alive at 8 years. No clinically apparent systemic metastases were encountered.

10601 Background: Brachial plexopathy is a well-recognized complication of breast cancer, most attributed to late effects of radiation. However, direct involvement of brachial plexus by recurrent breast cancer occurs. Misdiagnoses may lead to inappropriate attribution of the plexopathy to radiation, and therefore inappropriate therapy. Methods: We report fourteen cases of brachial plexopathy secondary to breast cancer diagnosed at the Mayo Clinic-Rochester from 2003 to 2005. Results: Thirteen of fourteen primary tumors and 12/14 recurrences were ER/PR positive. Only 1/14 patient had Her 2 neu overexpression. The median time from the original breast cancer diagnosis to first brachial plexus symptom was 14 years. The median time from the development of symptoms to diagnosis was 8 months with the range being 1 month to 8 years. MRI revealed a distinct mass in 3/13 patients, plexus thickening in 5/13, and was normal in 5/13. Only 5/13 original MRI interpretations suggested tumor. In four patients that the 1.5 T MRI was either interpreted as normal or unlikely cancer the 3 Tesla MRI revealed abnormal uptake suggestive of malignancy. PET scan suggested malignancy in 3/6 patients. Two of these cases had other metastatic disease. In the other three cases that PET scans were done the uptake was mild, suggesting inflammation rather than malignancy. Reinterpretations of the PET scan and MRI in combination by an experienced musculoskeletal radiologist was highly suggestive of malignancy in all cases. Definitive diagnosis was eventually obtained by biopsy of the brachial plexus (7/14) or another site of metastasis in (4/14). Conclusions: The often slowly progressive nature of hormonally driven breast cancer can mimic radiation induced brachial plexopathy. In the cases reviewed, PET was not reliable in differentiating inflammation from tumor. MRI findings are nonspecific and higher resolution 3T MRI may be needed to detect an abnormality. Interpretation of MRI and PET together is useful. Patients with a history of breast cancer, and brachial plexus symptoms should be carefully evaluated with consideration for recurrent disease as a cause. Biopsy of the brachial plexus can be done safely and has an important role in diagnosis. No significant financial relationships to disclose.

Background: Neurolymphomatosis (NL) is a highly rare disorder defined as infiltration of peripheral nervous system by a lymphoproliferative neoplasm, both presented as the first manifestation of the malignancy (primary NL) or as a site of disease progression or relapse (secondary NL). Due to rarity of this disorder data on clinical features, best approach and outcome are limited. Furthermore diagnosis of this disease is often uncertain and based on radiological images only. Methods: We retrospectively reviewed clinical records of all histologically confirmed-NL, diagnosed and treated at the Division of Hematology of Mayo Clinic in Rochester, MN between January 2002 and December 2018. Clinical features and outcome were analyzed. Responses to therapy were assessed by post-treatment radiological changes and clinical symptoms improvement. Survival analysis such as progression free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier curves with log-rank test. Comparison between subgroups was investigated using Fisher's exact test and Wilcoxon test for categorical and continuous variables, respectively. Results: Over a 16-year period 40 patients with biopsy-proven NL were included in study. Primary and secondary NL were 19 (48%) and 21 (52%) respectively, with a median age of 60.5 years (range 37-83) and male sex 24/40 (60%). The predominant histology was represented by B-cell lymphomas (39/40, 97%) with a vast majority large B-cell lymphoma (LBCL) 27/40 (67%) and only 1 case of T-cell lymphoma. The affected structures included brachial plexus (12/40, 35%), lumbosacral plexus (5/40, 12%), cauda equine and nerve roots (14/40, 35%), sciatic nerve (12/40, 30%), femoral nerve (4/40, 10%), cranial nerves (8/40, 20%), multiple nerves involved in 23/40 (57%). Four out of 40 cases had brain involvement and cerebrospinal fluid (CSF) was positive in 7/29 (24%). NL clinical manifestations included muscular weakness (33/4, 82%), sensory deficit (32/40, 80%), pain (28/40, 70%) and autonomic dysfunction (3/40, 7%). Magnetic resonance imaging (MRI) detected neural abnormalities in 35/36 cases (97%), CT imaging identified disease in 3/8 (37%) and FDG-PET scan was positive in 22/31 (71%); electromyography showed some grade of neuropathy in 28/29 (97%). Treatment included systemic chemotherapy in 38/40 (95%) cases, containing high dose methotrexate (HD-MTX) in 26/40 (65%) and rituximab in 20/40 (50%); 11/39 (28%) patients underwent consolidative autologous stem cell transplant (ASCT); 4/40 received consolidative radiotherapy (RT), 1/40 was treated with RT alone; intrathecal chemotherapy was infused in 1/40 cases; one patient with solely great auricular nerve NL involvement was cured with surgery only. Treatment efficacy evaluated by imaging and clinical improvement consisted with an overall response rate (ORR) of 73% (27/37) with a 24% (9/37) of complete remission (CR); No statistical difference in rate of response was observed by different systemic treatments. Of note, patients undergoing HDC-ASCT consolidation obtained 100% of ORR (n=10) versus 61.5% (n=16) achieved by others (P=0.03). With a median follow up of 45.1 months (range 0.5-186.7) a 36 months-OS of 77% (95% CI, 60-88) was observed for the whole cohort. A trend of longer survival rate for primary NL was observed, with a 36-month OS of 95% (95% CI, 72-99) vs. 55% (95% CI, 30-77) for secondary NL (p 0.134). A strong benefit in terms of outcome was observed for patients receiving rituximab-containing regimens with a 36 months-PFS of 72% (95% CI, 55-92) vs 28% (95% CI, 12-53) (P=0.001), and a 36 months-OS of 87% (CI 95%, 60-98) vs. 65% (95% CI , 41-84) (P=0.04) (figure 1); no survival difference was observed for patients treated with systemic therapy containing HD-MTX vs. others. ASCT consolidation was associated with a trend of improved survival with a 36 months-PFS of 69% (95% CI, 35-90) vs. 47% (95% CI, 29-66) for others (P=0.09). Conclusions: With the limit of a retrospective analysis, LBCL represent the predominant histologic subtype of NL; MRI and FGD-PET appeared to be the most accurate radiological tools to detect neural disease. Systemic treatments including rituximab should be preferred, HD-MTX seems to be not so effective while ASCT consolidation may be considered in selected patients. Due to the spare number of cases treated with RT its role cannot be clarified by our study. Disclosures Nowakowski: NanoString: Research Funding; MorphoSys: Consultancy, Research Funding; Genentech, Inc.: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Curis: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees.