Cavernous Malformation of the Optic Nerve and Chiasm: Prompt Suspicion and Surgery Matter.

BACKGROUND: Cavernous malformations (CMs) of the optic nerve and chiasm are extremely rare, accounting for less than 1% of all intracranial CMs. Acute, subacute, or progressive visual loss from CM may occur with or without hemorrhage. Prompt surgical excision of the CM offers the best hope to improve or stabilize vision. Given its rarity, optic nerve and chiasm CMs may not be readily suspected. We provide 3 cases of optic nerve and chiasm CM, highlighting key neuroimaging features and the importance of expedited intervention. METHODS: Case records of the neuro-ophthalmology clinics of the Bascom Palmer Eye Institute and the University of Colorado, and literature review of reported cases of optic CM. RESULTS: A 49-year-old woman reported acute progressive painless vision loss in the right eye. MRI showed a suprasellar mass with heterogeneity in signal involving the right prechiasmatic optic nerve. Surgical excision of the CM 5 days after onset of visual loss improved vision from 20/300 to 20/30. A 29-year-old woman with acute painless blurred vision in the right eye had anterior chiasmal junctional visual field defects corresponding to a heterogeneously minimally enhancing mass with blood products enlarging the optic chiasm and proximal right optic nerve. Surgical excision of the CM 8 weeks after onset of visual loss improved vision from 20/40 to 20/15 with improved visual fields. A 33-year-old woman with a history of familial multiple CMs, diagnosed at age 18, reported new-onset severe headache followed by blurred vision. MRI showed a hemorrhagic lesion of the optic chiasm and right optic tract. She was 20/20 in each eye with a reported left superior homonymous hemianopia. No intervention was recommended. Vision of the right eye worsened to 20/400 2 months later. The patient was followed over 13 years, and the MRI and visual function remained unchanged. Literature review yielded 87 optic CM cases occurring across gender and nearly all ages with visual loss and headache as the most common presenting symptoms. Optic chiasm is the most common site of involvement (79%). Nearly 95% of reported CM cases were treated with surgery with 81% with improved vision and 1% with worsened vision. CONCLUSION: MRI features are critical to the diagnosis of optic nerve and chiasm CM and may mimic other lesions. A high index of suspicion by the neuro-ophthalmologist and neuroradiologist leads to early recognition and intervention. Given optic CM displaces and does not infiltrate neural tissue, expedited surgical resection by a neurosurgeon after consideration of other diagnostic possibilities improves visual function in most cases.

Papillary Squamous Cell Carcinoma of the Uterine Cervix: Biopsy Samples Frequently Underrepresent the Presence of Stromal Invasion.

Papillary squamous cell carcinoma is a rare variant of squamous cell carcinoma, histologically characterized by thin or broad papillae lined by epithelium showing the features of high-grade squamous intraepithelial lesion. Given the exophytic nature of these neoplasms, the diagnosis, assessment and quantification of invasion may be difficult in small biopsies. The goal of this study was to determine the presence and extent of cervical stromal invasion by comparing biopsy samples with excisional specimens in a cohort of patients diagnosed with papillary squamous cell carcinoma. Cases were identified from the surgical pathology files between the years 2003 and 2018 and only cases in which the patients underwent an excisional procedure following the diagnostic biopsy were included. Eighteen cases were identified. Patients age ranged 21 to 72 yr (mean: 46.2 yr). Review of the initial, presurgical biopsies showed that 17/18 (94%) patients had no evidence of stromal invasion. In the surgical excision specimens (2 cone biopsies, 1 loop electrosurgical excision procedure, and 15 hysterectomies), 13 cases (76.5%) showed invasive squamous cell carcinoma. Tumor sizes ranged 1.0 to 6.1 cm; stromal invasion ranged in depth 0.2 to 2.2 cm (median: 1.2), and in horizontal length 0.3 to 4.0 cm (median: 2.01). Papillary squamous cell carcinoma is a rare variant of squamous cell carcinoma of the cervix that may impose some diagnostic difficulties in small biopsies. Our findings demonstrated that the significant majority of cases might only show the presence of invasive cancer in excisional samples. Awareness of this data is important to guide proper management and avoid under-treatment.

Pseudocarcinomatous Squamous Hyperplasia Involving Bone: A Diagnostic Pitfall Mimicking Squamous Cell Carcinoma.

BACKGROUND: Pseudocarcinomatous squamous hyperplasia (PSH) within the bone is uncommon and closely mimics well-differentiated squamous cell carcinoma (SCC). It arises from cutaneous or mucosal surfaces and grows directly into the bone. This study analyzes a large series of PSH and discusses the clinicopathologic features that facilitate its distinction from SCC. DESIGN: Cases were identified from the surgical pathology files between 1985 and 2020. RESULTS: The 31 cases included 21 males, 9 females, 1 unknown sex; who were 20 to 87 years old (average: 59 y). Sites included mandible-17, maxilla-5, toes-4, and 1 case from finger, femur, tibia, ischium, and unknown. Fourteen patients had a history of SCC, 13 treated with resection and chemoradiation and developed infected osteoradionecrosis, 4-medication-related osteonecrosis, 3-peripheral vascular disease, and diabetes mellitus, 3-trauma, 3-osteomyelitis, 3-unknown, and 1-hematologic malignancy. All cases exhibited severe osteomyelitis and nests of reactive keratinizing squamous epithelium that matured towards the bone surface, lacked significant atypia, or mitotic activity but permeated the medullary cavity. Patients with previous SCC developed PSH after 2 months to 8 years (average: 4 y). Nineteen of 30 patients had follow-up (2 to 48 mo, average: 17 mo); 6 patients experienced repeated debridements over 2 months to 1 year; no patient developed SCC. CONCLUSIONS: PSH involving bone is infrequent, complicates severe osteomyelitis, and is often therapy related. The clinical findings are usually not concerning for malignancy, however, the histologic findings are an important diagnostic pitfall because they mimic SCC.

Epithelioid Sarcoma of the Peripheral Nerve: Clinicopathologic Series of Three Cases and Literature Review.

OBJECTIVES: Epithelioid sarcoma (ES) rarely arises in the nerve. To increase our understanding of this unusual tumor originating in the nerve, we describe the features of three cases and review the literature. METHODS: Clinical data, imaging, pathology, treatment, and follow-up are detailed. A systematic literature review was conducted. RESULTS: Two patients were male and one female; the median age was 24 years. The patients had neurologic symptoms, and the tumors arose in large nerves and ranged from 2.4 to 5.8 cm. The tumors were avid on positron emission tomography-computed tomography and showed increased signal intensity on T2-weighted magnetic resonance imaging. Centered in the nerve, the tumors grew with an infiltrative pattern and encased the nerve fascicles. All were treated with wide resection, and adjuvant treatment included combinations of chemotherapy and radiation. One recurred, and the limb was amputated. Metastases were documented to lymph nodes, lung, pleura, and skin. One patient died of disease after 54 months. Literature review including our cases showed that tumors stained with pancytokeratin (9/9), EMA (4/4), and CD34 (7/7); there was loss of INI1 in all six cases tested. CONCLUSIONS: ES rarely arises in the peripheral nerve, and its infiltrative nature often requires morbid surgery. The differential includes a variety of benign and malignant epithelioid neoplasms.

Clear Cell Change in Reactive Angiogenesis: A Potential Diagnostic Pitfall.

Reactive angiogenesis is commonplace, occurs in many circumstances, and is important in the repair of injured tissue. Histologically, it is characterized by newly formed capillaries arranged in a lobular architecture and lined by plump endothelial cells. We have encountered a form of reactive angiogenesis not well described; composed of large endothelial cells with abundant clear cytoplasm that causes diagnostic challenges. The cohort includes 10 patients, aged 4 to 61, mean 40 years; 7 males, 3 females. One case involved bone (ilium), and 9 involved soft tissue: fingers (n=2), toes (n=2), hip joint (n=1), shoulder (n=1), thigh (n=2), and anal mucosa (n=1). Clinically, the patients had chronic ulcers, osteomyelitis, or localized infection. All cases exhibited a lobular proliferation of capillaries lined by large polyhedral endothelial cells that obscured the vessel lumens and were admixed with acute and chronic inflammation. The endothelial nuclei were vesicular with small nucleoli and the cytoplasm was abundant and clear or palely eosinophilic. The endothelial cells were stained with CD31 and ERG (7/7 cases), CD34 (6/6), FLI1 (4/4), and were negative for keratin and CD68 (6/6). Periodic acid-Schiff stain and periodic acid-Schiff stain-diastase on 3 cases did not demonstrate glycogen. Using a polymerase chain reaction, no Bartonella henselae was found in all 6 cases tested. Reactive angiogenesis with clear cell change unassociated with Bartonella spp. has not been described. It causes diagnostic challenges and the differential diagnosis includes benign and malignant tumors, as well as unusual infections. It is important to distinguish between these possibilities because of the significant impact on treatment and prognosis.

Arsenic toxicity manifesting as profuse watery diarrhea during induction therapy for acute promyelocytic leukemia.

Arsenic trioxide (ATO) is generally well tolerated for treatment of APL. We present a patient with severe watery diarrhea and pancreatitis thought to be due to ATO toxicity in the setting of obesity and acute kidney injury. Future studies evaluating ATO levels in patients experiencing toxicities may help guide dose modifications.

Epithelioid Hemangioendothelioma of the Bowel in Crohn's Disease: The First Reported Case.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is an uncommon malignant endothelial neoplasm that most commonly arises in soft tissue, bone, lung, and liver. Crohn's disease (CD) is an inflammatory bowel disease of unknown etiology that is frequently associated with complications including strictures, fistulas/fissures, and neoplasms. CASE DESCRIPTION: A 43-year-old woman with a 6-year history of severe CD presented with anal pain and bleeding. She had prior partial colectomy for a stricture and a diverting ileostomy for perianal fissures and stricture. Colonoscopy showed severe chronic active colitis, stricture at 30 cm of anal verge, and a perianal fistula. The patient underwent total proctocolectomy. The colonic mucosa exhibited segmental ulceration and irregular thickening of the colon wall. Beneath an ulcer of the anal canal within the muscularis propria was a 1.2-cm poorly circumscribed, firm, white-tan mass. The mass was composed of cords and groups of large epithelioid endothelial cells with intracytoplasmic vacuoles enmeshed in a myxohyaline stroma. Immunohistochemically, the tumor cells were positive for ERG, CD31, and CAMTA1 and focally positive for keratin and SMA. Next-generation sequencing revealed a WWTR1-CMATA1 fusion. The morphology, immunoprofile, and molecular genetics were diagnostic of EHE. DISCUSSION: Long-standing inflammatory bowel disease is associated with significant risk for developing neoplasms, usually carcinomas, which can be indistinguishable radiologically and clinically from nonneoplastic complications. These tumors are often identified as an incidental finding in specimens resected for clinically severe disease. This is the first report of EHE arising in the bowel affected by CD, and it mimicked mural fibrosis and fissures.