| Identifier |
walsh_2018_s1_c4 |
| Title |
A Tough Nut to Crack! - Video |
| Creator |
Lauren Maloley; Sachin Kedar; Deepta Ghate; Dominick DiMaio; Jason Helvey; Sachin Kedar |
| Affiliation |
(LM) (SK) (DG) (DD) (JH) (SK) University of Nebraska Medical Center, Omaha, Nebraska |
| Subject |
Horner's syndrome, Abducens Nerve Palsy, Skull base tumors, Sphenoid sinus |
| Description |
An excisional biopsy was performed using transnasal transphenoidal approach. Histopathology showed sheets of atypical epitheloid-appearing cells with extensive areas of necrosis and absence of glandular or squamous differentiation. The tumor cells had a high nuclear to cytoplasm ratio and small nucleoli. An extensive battery of immunohistochemistry staining was inconclusive and contradictory. Multiple epithelial and lymphoma immunostains were negative. A preliminary diagnosis of melanoma was suggested based on diffuse positive staining for SOX10. However, lack of staining for additional melanocytic markers including S100, HMB45, Melan A and MiTF argued against that diagnosis. Conventional cytogenetics demonstrated a translocation involving 15q and 19p. Fluorescence in situ hybridization (FISH) studies were positive for fusion of the NUTM1 (15q14) and BRD4 (19p13.12) loci. Although the immunohistochemistry staining was unusual, the FISH studies and cytogenetics are diagnostic of a NUT (nuclear protein of the testis) carcinoma. PET-CT scan showed increased uptake of two cervical lymph nodes. She is currently undergoing treatment with radiation to the sella/sphenoid with concurrent chemotherapy (cisplatin and docetaxol). NUT carcinoma is an exceedingly rare malignancy with fewer than 100 reported cases. It is a poorly characterized squamous cell carcinoma, which arises in midline structures of the head and neck and thorax. The tumor is highly aggressive, with greater than 50% demonstrating metastasis (to lymph nodes and bones) at diagnosis. Diagnosis is made by the demonstration of a pathognomonic translocation of the NUTM1 gene on chromosome 15, most often to BRD4 gene on chromosome 19, forming a BRD4-NUT fusion oncogene on cytogenetic studies. Unfortunately, there is no established or effective treatment regimen and median survival remains between 6.7-9 months. Recent advances in understanding the molecular biology of NUT carcinoma have led to promising novel targeted therapies, such as histone deacetylase (HDAC) inhibitors or bromodomain (BRD) inhibitors which induce squamous differentiation. |
| History |
A 47-year-old previously healthy female was transferred to our facility when she developed left abducens nerve palsy during treatment of intractable sinusitis. Two weeks prior to presentation, she developed headache and sinus congestion. She was treated with amoxicillin-clavulanic acid and prednisone for acute sinusitis at a local urgent care facility. Her symptoms worsened and she was referred to an otolaryngologist who noted bloody material on nasal endoscopy and prescribed clindamycin and dexamethasone. The headache worsened and a week later, she developed blurred vision in the left eye. She was admitted to an outside facility and treated with intravenous levaquin and methylprednisolone. A maxillofacial and head CT was reported to show "complete opacification of bilateral sphenoid and right maxillary sinuses with mucosal thickening in the posterior ethmoid sinus and no intracranial abnormalities". Nasal endoscopy demonstrated edematous turbinates and mucosanguineous drainage from the right sphenoid ostium; no nasopharyngeal masses were seen. Baseline labs were unremarkable except mild elevation of white cell count (13.3 x 10^9 cells/L) and C-reactive protein (20.6 mg/L). At transfer, neuro-ophthalmic examination included a visual acuity of 20/25 OU, left Horner's syndrome and left esotropia with bilateral abduction deficits (worse left eye). Visual fields showed non-specific scatter. Fundus examination was normal. Corneal and facial sensations were intact. MRI brain and orbits showed a contrast enhancing sellar mass with extension superiorly to the hypothalamus, laterally into bilateral cavernous sinuses, anteriorly into the sphenoid sinus and inferiorly into the clivus. Treatment with broad-spectrum antibiotics-vancomycin, ceftriaxone and metronidazole was started. Extensive studies for autoimmune and infectious conditions (including fungal) were unremarkable. She underwent bilateral sphenoidotomy and right maxillary anstrostomy. Pathology showed nonspecific reactive changes and necrotic debris with negative cultures. A procedure was performed. |
| Disease/Diagnosis |
Nuclear protein of the testis (NUT) carcinoma |
| Presenting Symptom |
A 47-year-old previously healthy female was transferred to our facility when she developed left abducens nerve palsy during treatment of intractable sinusitis. Two weeks prior to presentation, she developed headache and sinus congestion. She was treated with amoxicillin-clavulanic acid and prednisone for acute sinusitis at a local urgent care facility. Her symptoms worsened and she was referred to an otolaryngologist who noted bloody material on nasal endoscopy and prescribed clindamycin and dexamethasone. The headache worsened and a week later, she developed blurred vision in the left eye. She was admitted to an outside facility and treated with intravenous levaquin and methylprednisolone. A maxillofacial and head CT was reported to show 'complete opacification of bilateral sphenoid and right maxillary sinuses with mucosal thickening in the posterior ethmoid sinus and no intracranial abnormalities'. Nasal endoscopy demonstrated edematous turbinates and mucosanguineous drainage from the right sphenoid ostium; no nasopharyngeal masses were seen. Baseline labs were unremarkable except mild elevation of white cell count (13.3 x 10^9 cells/L) and C-reactive protein (20.6 mg/L). At transfer, neuro-ophthalmic examination included a visual acuity of 20/25 OU, left Horner's syndrome and left esotropia with bilateral abduction deficits (worse left eye). Visual fields showed non-specific scatter. Fundus examination was normal. Corneal and facial sensations were intact. MRI brain and orbits showed a contrast enhancing sellar mass with extension superiorly to the hypothalamus, laterally into bilateral cavernous sinuses, anteriorly into the sphenoid sinus and inferiorly into the clivus. Treatment with broad-spectrum antibioticsvancomycin, ceftriaxone and metronidazole was started. Extensive studies for autoimmune and infectious conditions (including fungal) were unremarkable. She underwent bilateral sphenoidotomy and right maxillary anstrostomy. Pathology showed nonspecific reactive changes and necrotic debris with negative cultures. A procedure was performed. |
| Date |
2018-03 |
| References |
1) Bair RJ, Chick JF, Chauhan NR, et al. Demystifying NUT midline carcinoma: radiologic and pathologic correlations of an aggressive malignancy. AJR. 2014;203(4): 391-399. 2) Diffalha SA, Aukla NA, Hasan S, et al. NUT midline carcinoma: a rare malignancy. Cancer Control. 2017;24(2): 202-206. 3) Edgar M, Caruso AM, Kim E, et al. NUT midline carcinoma of the nasal cavity. Head Neck Pathol. 2016;11: 389-392. 4) Hellquist H, French CA, Bishop JA, et al. NUT midline carcinoma of the larynx: an international series and review of the literature. Histopathology. 2017;70: 861-868. 5) Lemelle L, Pierro G, Freneaux P, et al. NUT carcinoma in children and adults: a multicenter retrospective study. Pediatr Blood Cancer. 2017;64(12): 1-9. 6) Sun H, McGuire MF, Zhang S, et al. NUT midline carcinoma: morphoproteomic characterization with genomic and therapeutic correlates. Ann Clin Lab Sci. 2015;45(6): 692-701. 7) Wasserman JK, Purgina B, Sekhon H, et al. The gross appearance of a NUT midline carcinoma. Int J Surg Pathol. 2016;24(1): 85-88. |
| Language |
eng |
| Format |
video/mp4 |
| Type |
Image/MovingImage |
| Source |
2018 North American Neuro-Ophthalmology Society Annual Meeting |
| Relation is Part of |
NANOS Annual Meeting 2018 |
| Collection |
Neuro-Ophthalmology Virtual Education Library: Walsh Session Annual Meeting Archives: https://novel.utah.edu/Walsh/ |
| Publisher |
North American Neuro-Ophthalmology Society |
| Holding Institution |
Spencer S. Eccles Health Sciences Library, University of Utah |
| Rights Management |
Copyright 2018. For further information regarding the rights to this collection, please visit: https://NOVEL.utah.edu/about/copyright |
| ARK |
ark:/87278/s6nw3ms8 |
| Setname |
ehsl_novel_fbw |
| ID |
1320245 |
| Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6nw3ms8 |
