Anders, Carey K.

Budwit, Debra

Chandramouleeswaran, Sindu

Lim, Ming Y.

Zagar, Timothy M.

PubMed

Carolina Digital Repository

Isolated Cranial Mononeuropathy: An UnusualInitial Presentation and Disease Progressionof Metastatic Carcinoma of the BreastCase ReportA previously healthy 46-year-old woman presented in April 2010with a 1-month history of right facial paresthesia with pain over themaxillary region. She began receiving carbamazepine for presumedtrigeminal neuralgia and experienced some improvement of symp-toms. Her neurologic symptoms persisted and she underwent a brainmagnetic resonance imaging (MRI) scan that revealed a 2.2  1.3 cmmass within Meckel’s cave that extended along V2 and V3 branches ofthe trigeminal nerve; this was concerning for perineural spread oftumor from a nasopharyngeal or salivary gland tumor.A sinonasal endoscopy was performed and was essentially nor-mal. Additional imaging with a dedicated cranial nerve brain MRIdemonstrated the previously identified mass in Meckel’s cave withextension of abnormal enhancement and thickening involving thecisternal portion of the trigeminal nerve and along V2 and V3 (Figs 1Aand 1B, arrows). Multiple lytic lesions at the posterior vertex of theskull, the clivus, the right lateral aspect of C1, the dens, and the body ofC2 were also identified. A positron emission tomography with con-current computed tomography (PET/CT) revealed a 3.5  2.1 cmintensely 18F-fluorodeoxyglucose (FDG) –avid left medial breastmass, and two moderately FDG-avid masses measuring 2.7  2.0cm and 1.2  0.9 cm, in the upper outer quadrant of the rightbreast. There were also widespread lytic lesions in the thoracicosseous structures, in addition to the known lytic lesions in theskull base. Taking all this together, metastatic breast cancer was thepresumed diagnosis.The patient denied any nipple discharge, breast pain, mass, infec-tion, or trauma. Her most recent mammogram a year before wasreportedly normal. Her medical history was only significant for re-moval of a dermoid ovarian cyst 10 years before. She reached men-arche at age 12 years and had been prescribed the oral contraceptivepill for 10 years. Her first child was born when the patient was age 38years, and she reached menopause at age 44 years. She did not requirehormone replacement therapy. Family history was significant for lungcancer and bladder cancer in two uncles, with no family history ofbreast or ovarian cancer. Her BRCA mutation status is unknown.Physical examination was significant for reduced sensation totouch over the right maxillary facial region, with no other cranial nerveabnormalities. The rest of the neurologic examination was normal.Breast examination revealed a mobile, nontender, 3 cm mass in theright upper outer quadrant and an irregular 2  3 cm mass in the leftupper inner quadrant. A diagnostic mammogram demonstrated aspiculated mass with architectural distortion and microcalcificationsmeasuring 8.0  5.8  7.4 cm in the left upper inner quadrant and amacrolobular mass within the right upper outer quadrant. Breastultrasound revealed a 2.8  2.1  1.7 cm spiculated, hypoechoic massin the left breast and a 3.4  2.1  1.5 cm macrolobular, hypoechoicmass in the right upper outer breast.Ultrasound-guided core biopsy of the left breast mass revealed agrade 2 (Nottingham), estrogen receptor (ER) –positive (90%, strongintensity), progesterone receptor (PR) –negative, and human epider-mal growth factor receptor 2 (HER2)/neu –negative (1 via immu-nochemistry [IHC]) infiltrating ductal carcinoma (Fig 2A,hematoxylin and eosin staining, 400 magnification). Interestingly,ultrasound-guided core biopsy of the right breast mass revealed amorphologically distinct, ER-positive (95%, strong intensity), PR-positive (90%, strong intensity), and HER2/neu-negative (0 via IHC)infiltrating ductal carcinoma, signet ring cell variant with abundantintracytoplasmic mucin and eccentrically placed nuclei (Fig 2B,hematoxylin and eosin staining, 400 magnification). Fine-needleaspiration of the right ilium lesion revealed metastatic breast adeno-carcinoma similar to that present in the left breast primary cancer,with a similar immunophenotypic receptor profile (positive for ER[93%], negative for PR, and HER2/neu was not overexpressed).Signet ring cells were not identified in the bone metastasis.With involvement of the trigeminal nerve, lumbar puncture wasperformed. CSF analysis revealed a cell count of 1/L, protein concen-tration of 75 mg/dL, and glucose concentration of 74 mg/dL; cytologydid not demonstrate any malignant cells present. These findings werenot consistent with a diagnosis of leptomeningeal carcinomatosis.Neither CA-15.3/27.29 nor CA-125 was tested on the CSF. Given thepatient’s persistent neurologic symptoms, she received palliative radi-ation to the base of the skull via opposed lateral beams, with 3 Gy over10 fractions for a total dose of 30 Gy over a 2-week period. Given theendocrine-sensitive and HER2/neu-negative nature of her tumor andher postmenopausal status on the basis of follicle stimulating hor-mone, luteinizing hormone, and estradiol laboratory parameters, shewas prescribed an aromatase inhibitor, letrozole. For her bone metas-tases, monthly zoledronic acid infusions were initiated. She also con-tinued to receive narcotic therapy for pain, gabapentin for neuralgia,and corticosteroids and antiemetic therapy for supportive care.A BFig 1.JOURNAL OF CLINICAL ONCOLOGY D I A G N O S I S I N O N C O L O G YVOLUME 31  NUMBER 18  JUNE 20 2013e294 © 2013 by American Society of Clinical Oncology Journal of Clinical Oncology, Vol 31, No 18 (June 20), 2013: pp e294-e296By week 8 after initiation of radiation and systemic therapies, thepatient’s pain control had improved significantly, so that she was ableto self-discontinue narcotics and continued to receive gabapentin. At12 weeks, she underwent restaging studies. PET/CT imaging revealeda stable appearance of the left breast mass and decreased size of theright breast mass, with mixed responses of her widespread osseousmetastatic disease. She continued to receive letrozole and monthlyzoledronic acid infusion.In January 2011, repeat PET/CT imaging revealed an increase insize of the left breast mass and left axillary lymph node. The patient wasswitched to second-line endocrine therapy with fulvestrant (Faslodex;AstraZeneca, Wilmington, DE). Repeat imaging in May 2011 contin-ued to show disease progression, and she was switched to exemestane(Aromasin; Pfizer, New York, NY). In September 2011, she developeddiplopia and was found to have a right sixth cranial nerve palsy. Giventhat repeat lumbar puncture was negative for leptomeningeal carcino-matosis, it was thought that the sixth cranial nerve palsy was a result ofcompression by bony metastasis in the right clivus within the skull. Shewas transitioned to tamoxifen. Repeat imaging in January 2012 dem-onstrated disease progression with increased liver metastases, and shewas switched from endocrine therapy to chemotherapy with capecit-abine. In July 2012, she presented with new left maxillary paresthesia.Repeat brain MRI confirmed progression of disease with worseninginvolvement of the right trigeminal nerve and new involvement of theV2 and V3 branches of the left trigeminal nerve.Because the patient was symptomatic neurologically, the decisionwas made to reirradiate with an additional 2 Gy over seven fractionsfor a total dose of 14 Gy (with opposed lateral beams), which shetolerated well. This low dose was given to limit the cumulative dose tothe underlying optic apparatus. The patient has recently been transi-tioned to single-agent carboplatin chemotherapy, with reimagingscans scheduled at standard intervals.DiscussionAlthough uncommon, cranial mononeuropathy has been re-ported in the literature as a manifestation of metastatic neoplasms. Inthe majority of cases, the neuropathy is caused by either diffuse me-tastasis to the leptomeninges1 or dura mater,2 or direct intracranialextension from invasive head and neck tumors. Solitary metastasis toan isolated cranial nerve from a distant primary tumor is rare but hasbeen reported, particularly for trigeminal neuropathy in lung,3 lym-phoma,4 colorectal cancer,5 and breast cancer.6-9Similar to the reported cases, our patient presented initially withright trigeminal mononeuropathy, with improvement in symptomsafter local and systemic therapy. She subsequently developed rightabducens mononeuropathy and then left trigeminal mononeuropa-thy, indicating disease progression. Interestingly, throughout her clin-ical disease, she had no evidence of leptomeningeal carcinomatosis,which one would have expected, given the involvement of multiplecranial nerves. Although a paraneoplastic neuropathy could accountfor the multiple cranial nerve involvement,10 simultaneous neuropa-thies are usually reported and are not consistent with our patient’spresentation, given initial brain MRI findings. Moreover, our patienthad sequential involvement of multiple cranial nerves with diseaseprogression, which, to our knowledge, has not been reported previously.Another unique feature of our patient case is the presence ofsignet ring cells in the right breast biopsy. Signet ring cell carcinoma(SRCC) of the breast is uncommon, with an incidence of between 2%and 4.5% of total breast cancers.11,12 It is classified as a mucinouscarcinoma and is defined by more than 20% of the malignant cellsappearing as the signet ring form of tumor. On histology, metastaticgastric SRCC can be difficult to delineate from primary SRCC of thebreast. It is important to differentiate the two because of their differ-ence in prognosis. In our patient, the clinical presentation, the locationof primary tumor(s) in the breast, and IHC stains that stained stronglyfor ER all confirmed a primary breast SRCC.The prognosis of SRCC of the breast is unknown because of itsrarity, but the presence of signet ring cells is believed to be a poorprognostic factor. A study by Frost et al13 found that the presence of10% or more signet ring cells represents a poor individual prognosticfactor in stage I infiltrating lobular carcinomas. The pure form ofSRCC of the breast is also thought to be more aggressive than muci-nous, ductal, or lobular invasive carcinoma; in 24 patients with SRCC,60% survived less than 7 years.11 Because we were unable to biopsy thecranial lesions, we can only speculate whether having features of SRCCof the breast could have accounted for this unusual presentation, withisolated metastasis to multiple cranial nerves.In summary, we report the case of a patient with right facialparesthesia as the first clinical manifestation of metastatic breast can-cer. Our patient case serves as a reminder to consider metastaticABFig 2.Diagnosis in Oncologywww.jco.org © 2013 by American Society of Clinical Oncology e295disease as part of the differential diagnosis for patients presenting withtrigeminal neuropathy.Ming Y. Lim, Sindu Chandramouleeswaran,Timothy M. Zagar, Debra Budwit, and Carey K. AndersUniversity of North Carolina, Chapel Hill, NCAUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTThe author(s) indicated no potential conflicts of interest.REFERENCES1. Rubinstein MK: Cranial mononeuropathy as the first sign of intracranialmetastases. Ann Intern Med 70:49-54, 19692. Horton J, Means ED, Cunningham TJ, et al: The numb chin in breastcancer. J Neurol Neurosurg Psychiatry 36:211-216, 19733. Delaney P, Khoa N, Saini N: Isolated trigeminal neuropathy: An unusualcomplication of carcinoma of the lung. JAMA 237:2522-2523, 19774. Manon-Espaillat R, Lanska DJ, Ruff RL, et al: Visualization of isolatedtrigeminal nerve invasion by lymphoma using gadolinium-enhanced magneticresonance imaging. Neuroradiology 32:531-532, 19905. Mastronardi L, Lunardi P, Osman Farah J, et al: Metastatic involvement ofthe Meckel’s cave and trigeminal nerve: A case report. J Neurooncol 32:87-90,19976. Nakano I, Iwasaki K, Kondo A: Solitary metastatic breast carcinoma in atrigeminal nerve mimicking a trigeminal neurinoma: Case report. J Neurosurg85:677-680, 19967. Hirota N, Fujimoto T, Takahashi M, et al: Isolated trigeminal nervemetastases from breast cancer: An unusual cause of trigeminal mononeuropa-thy. Surg Neurol 49:558-561, 19988. Albayram S, Adaletli I, Selcuk H, et al: Breast cancer metastasis involvingpterygopalatine fossa: A cause of trigeminal neuralgia. Headache 44:927-928,20049. Morı́s G, Pérez-Peña M, Miranda E, et al: Trigeminal mononeuropathy: Firstclinical manifestation of breast cancer. Eur Neurol 54:212-213, 200510. Hammam T, McFadzean RM, Ironside JW: Anti-hu paraneoplastic syn-drome presenting as bilateral sixth cranial nerve palsies. J Neuroophthalmol25:101-104, 200511. Merino MJ, Livolsi VA: Signet ring carcinoma of the female breast: Aclinicopathologic analysis of 24 cases. Cancer 48:1830-1837, 198112. Hull MT, Seo IS, Battersby JS, et al: Signet-ring cell carcinoma ofthe breast: A clinicopathologic study of 24 cases. Am J Clin Pathol 73:31-35,198013. Frost AR, Terahata S, Yeh IT, et al: The significance of signet ring cellsin infiltrating lobular carcinoma of the breast. Arch Pathol Lab Med 119:64-68,1995DOI: 10.1200/JCO.2012.47.3322; published online ahead of print atwww.jco.org on May 13, 2013■ ■ ■Lim et ale296 © 2013 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY

Isolated Cranial Mononeuropathy: An Unusual Initial Presentation and Disease Progression of Metastatic Carcinoma of the Breast

http://dx.doi.org/10.1200/JCO.2012.47.3322

Isolated Cranial Mononeuropathy: An Unusual Initial Presentation and Disease Progression of Metastatic Carcinoma of the Breast

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