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The CERTAIN Study Results: Adjunctive p16 Immunohistochemistry Use in Cervical Biopsies According to LAST Criteria

Wright, T C; Stoler, M H; Ferenczy, A; Ranger-Moore, J; Fang, Q; Kapadia, M; Singh, S; Ridder, R
The Lower Anogenital Squamous Terminology (LAST) Project recommends the use of p16 immunohistochemistry as an adjunct to morphologic assessment of cervical biopsies according to a specific set of criteria. We analyzed the effect of adjunctive p16 according to LAST criteria in a US-based diagnostic utility study involving 70 surgical pathologists providing a total of 38,500 reads on cervical biopsies. Compared with the results obtained using hematoxylin and eosin-stained slides only, including p16-stained slides per LAST criteria increased sensitivity and specificity for diagnosing histologic high-grade squamous intraepithelial lesions across all cases by 8.1% (95% confidence interval [95% CI], 6.5-9.7; P<0.0001) and 3.5% (95% CI, 2.8-4.2; P<0.0001), respectively, using expert consensus diagnoses on hematoxylin and eosin+p16 as reference. Within the subset of cases classified by the pathologists as fulfilling the LAST criteria, adding p16 significantly increased both sensitivity (+11.8%; 95% CI, 9.5-14.0; P<0.0001) and specificity (+9.7%; 95% CI, 7.8-11.5; P<0.0001). However, a comparable improvement in sensitivity (+11.0%; 95% CI, 7.8-14.1; P<0.0001) was found when p16 was used in cases for which p16 staining was not ordered per LAST by the pathologists, whereas specificity decreased by -0.8% (95% CI, -1.1 to -0.5; P<0.0001). The study demonstrates a clinically and statistically significant increase in sensitivity and specificity for high-grade squamous intraepithelial lesion when p16 is used according to LAST criteria. Expanding the use of p16 into non-LAST cases would lead to a comparable improvement in sensitivity within this subgroup of biopsies, at the cost of a minimal, but statistically significant difference in specificity.
ISSN: 0147-5185
CID: 4992432

An acute T1 radiculopathy as result of a pull-up contest: A case report [Meeting Abstract]

Mastanduno, S; Marzolf, S; Fang, Q
Case Description: A 57-year-old male who had been doing weightlifting, "reverse" pull-ups, and strenuous neck motions presented after competing in a pull-up contest. After 20 pull-ups, he experienced a sudden electrical shock-like pain in his left upper scapular region with radiation to his left arm followed by whole arm burning. With pain gradually improved, he noticed weakness of left hand grip with numbness of ulnar side of forearm/hand. Without remarkable neck pain, he was given a clinical diagnosis of left brachial plexus injury and referred for electrodiagnostic test.
Setting(s): Clinic Patient: 57-year-old male Assessment/Results: Normal ulnar and medial antebrachial sensory nerve conduction were against lower trunk/medial cord injury. Electromyography (EMG) was indicative of left C8/T1 radiculopathy with evidence of partial denervation/reinnervation in abductor pollicis brevis, flexor carpi ulnaris, first dorsal interosseous, and C8/T1 paraspinal muscles. With negative EMG of finger extensors, T1 radiculopathy was suggested. Magnetic resonance imaging (MRI) showed left posterolateral disc herniation into T1-2 neuroforamina with compression of the exiting left T1 nerve root. Patient was educated on appropriate neck exercises and positioning. Three months post-injury patient reports improved left grip strength with resolution of pain and numbness.
Discussion(s): Isolated T1 radiculopathy is rarely reported as it is clinically and electrophysiologically difficult to separate from C8 radiculopathy. In our case, combined EMG result of positive C8/T1 muscles and negative C7/8 muscles with left T1 root compression on MRI confirmed T1 radiculopathy. The mechanism of injury in this patient is unclear, however, combined local muscles' fast contractions with prolonged neck hyperextension may have caused the T1/2 disc herniation.
Conclusion(s): T1 radiculopathy and disc herniation at T1-2 are not commonly reported and it may happen during strenuous pull-ups with improper cervical posture. With the overabundance of new exercise fads, many involving timed competitions, it is important to counsel patients on proper form to help prevent acute disc herniations
ISSN: 1934-1482
CID: 4454852

Unilateral polyradiculopathy related to herpes zoster: A case report [Meeting Abstract]

Galliano, J V; Fang, Q G
Case Description: 79 y/o non-diabetic man developed severe sensory impairment and weakness/diffuse muscle atrophy of right upper extremity following shingles on right forearm/hand. This right-handed patient first noticed painful shingles rashes on right forearm/hand. He was treated with Valtrex for 7 days and put on Gabapentin. Soon after he developed numbness of right fingers, except for 5th digit, along with weakness/muscle atrophy from right hand to the posterior forearm with a benediction hand and inability to make a full fist. Electrodiagnostic study revealed severe right Median and Radial sensorimotor neuropathies. Electromyography (EMG) revealed significant abnormal spontaneous activities on right Triceps, FCR, EIP, APB and FDI muscles and multilevel cervical paraspinal muscles at C5-T1. In contrast, EMG of left side was negative. The result is suggestive of multilevel root involvement, including at least C7, C8 and T1. The patient underwent extensive occupational therapy that improved the pain, swelling, ROM and function of right hand despite of persistence of the muscle atrophy. Setting: Outpatient clinics. Results or Clinical Course: The electrodiagnostic study is suggestive of motor herpes affecting multilevel cervical roots consistent with a polyradiculopathy of the affected side. Discussion: Herpes Zoster (HZ) is caused by reactivation of the varicella-zoster virus (VZV), which resides within the dorsal root ganglion (DRG) after clinical resolution of the primary VZV infection. Once reactivation occurs, it leads to painful, unilateral vesicular eruption within a dermatomal distribution. Segmental motor paresis develops in approximately 3 percent of patients with HZ and is felt to result from spread of the VZV from the DRG to the anterior root/horn. In this case, the positive EMG finding of cervical paraspinal muscles has supported the theory of virus spread into anterior horn affecting roots and peripheral motor nerves. Conclusions: While a polyradiculopathy secondary to HZ infecti!
ISSN: 1934-1482
CID: 1363042

Comparison of orthodromic and antidromic plantar nerve conduction studies: Three case reports [Meeting Abstract]

Troy, D E; Burkard, G P; Fang, Q G
Case Description: Three patients were referred to Electromyography (EMG) Lab for evaluation of Tarsal Tunnel Syndrome (TTS) after symptoms of foot pain. A 26-year-old man (case 1) had pain as sole symptom. Cases 2 (a 35-year-old man) and 3 (a 48- year-old woman) both had pain with numbness and tingling at the soles. Case 3 had previously received cortisone injections to tarsal tunnels that relieved foot pain significantly. All cases received the following studies: orthodromic and antidromic plantar nerve conduction studies (PNCS), Tibial and Peroneal motor nerve conductions (MNC), Sural and Superficial Peroneal sensory nerve conductions, and needle EMG for lower extremities and lumbar paraspinals. Both orthodromic and antidromic studies tested the medial and lateral plantar nerves and measured 14 cm distance between the cathode and stimulating electrodes. Setting: Outpatient Clinic. Results or Clinical Course: In case 1, the studies were normal, including orthodromic and antidromic both demonstrating good sensory nerve action potentials (SNAP) with the negative peak amplitudes at 6.7-14.2 microvolts orthodromically and at 9.0-23.4 microvolts antidromically. Cases 2 and 3 both showed abnormal Tibial MNC to Abductor Hallucis Longus (AHL). In addition, case 3 had positive EMG findings in AHL bilaterally. In both cases, none of the orthodromic studies had reproducible SNAP, however, all of the antidromic studies elicited reproducible SNAP that showed prolonged latency and/or reduced amplitude, indicative of a neuropathy. Discussion: TTS has been difficult to evaluate with NCS or EMG due to poor sensitivity and specificity. Orthodromic PNCS with recording at the ankles and antidromic PNCS with recording at the toes often yields poor responses even in normal individuals, especially in the elderly. Antidromic PNCS with recording at soles are often interfered by motor nerve responses, however, by titrating down the stimulation intensity, the reproducible SNAP can be separated. In the above cases, the a!
ISSN: 1934-1482
CID: 1363052