Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction.

Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary medical centers and perform DNA/RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to identify biomarkers of aggressive thyroid malignancy. We identify high-risk mutations and discover a unique molecular signature of aggressive disease, the Molecular Aggression and Prediction (MAP) score, which provides improved prognostication over high-risk mutations alone. The MAP score is enriched for genes involved in epithelial de-differentiation, cellular division, and the tumor microenvironment. The MAP score also identifies aggressive tumors with lymphocyte-rich stroma that may benefit from immunotherapy. Future clinical profiling of the stromal microenvironment of thyroid cancer could improve prognostication, inform immunotherapy, and support development of novel therapeutics for thyroid cancer and other stroma-rich tumors.

Mechanic Hands/Hiker Feet in a Patient With Amyopathic Dermatomyositis and Interstitial Lung Disease.

ABSTRACT: A 30-year-old African American woman with a history of interstitial lung disease presented with bilaterally symmetrical, nonpruritic, scaling and fissuring, hyperpigmented, lichenified plaques on her hands and feet. She reported occasional erythema of her face, intermittent erythema, and irritation of her eyes but denied any muscle weakness. A biopsy of the plantar first toe showed hyperkeratosis, striking alternating ortho- and parakeratosis with underlying apoptotic bodies. There was psoriasiform acanthosis without suprapapillary thinning, numerous apoptotic keratinocytes in all layers of the epidermis extending into the corneum that were out of proportion with the minimal interface inflammation. Colloidal iron and Alcian blue stains showed increased dermal mucin deposition. Given the clinical, histopathological, and supportive serological findings (positive anti-KU and anti-SSA), a diagnosis of clinically amyopathic dermatomyositis with mechanic hand/hiker feet (MH/HF) was rendered. The pseudocheckerboard pattern of MH/HF has been previously reported in only 4 patients. The most frequent associations with MH/HF are dermatomyositis and antisynthetase syndrome; however, our patient was negative for antiaminoacyl transfer RNA synthetase antibodies, a required criterion to diagnose antisynthetase syndrome. It is imperative to recognize MH/HF clinically and histopathologically because it may be an early indication of developing dermatomyositis or other connective tissue diseases, which would guide further workup and screening for systemic involvement of the disease, including interstitial lung disease.

Civatte Bodies in Pediatric Esophageal Biopsies: Does Lichen Esophagitis Pattern Occur in Children?

PURPOSE AND CONTEXT: Civatte bodies (CB) are associated with cutaneous and mucosal lichen planus in adults. They are a distinct feature of Lichen Esophagitis Pattern, which is not well described in children. We characterized clinicopathologic associations of archival esophageal CB at our Children's Hospital to determine whether lichen planus or Lichen Esophagitis Pattern occurs in children. METHOD: Pathology records were queried for pediatric esophageal biopsy diagnoses containing "CB," "apoptosis, "necrosis," or "dyskeratosis." Cases with concurrent eosinophilic/acute esophagitis were excluded. H&E slides and clinical reports were reviewed. KEY RESULTS: Biopsies with CB or similar were identified from 19 patients and had been termed "dyskeratotic cells" in 8 reports. Patients had variable age and presenting symptoms, male predominance (74%), and frequent clinical history of polypharmacy (47%), Crohn disease (42%), and/or celiac disease (21%). Civatte bodies were prominent in the distal esophagus (95%), as few isolated cells (63%), and with variable chronic inflammation (absent, pauci-inflammatory, and lichen planus-like in approximately one-third of cases each). CONCLUSIONS: We show that esophageal CB from pediatric patients are under-recognized and may have different features and implications compared to Lichen Esophagitis Pattern in adults. Recognition and documentation of pediatric esophageal CB is needed to understand their clinical significance.

Low Grade Papillary Sinonasal (Schneiderian) Carcinoma: A Series of Five Cases of a Unique Malignant Neoplasm with Comparison to Inverted Papilloma and Conventional Nonkeratinizing Squamous Cell Carcinoma.

There have been a few case reports and one small series of low grade papillary sinonasal (Schneiderian) carcinomas (LGPSC) which mimic papillomas but have overtly invasive growth and which occasionally metastasize. We describe the morphologic, clinical, immunohistochemical, and molecular features of five patients with LGPSC compared with eight cases each of inverted papilloma (IP) and conventional nonkeratinizing squamous cell carcinoma (SCC) with papillary growth. All LGPSC were nested with predominantly pushing invasion, no stromal reaction, and frequent surface papillary growth. All consisted of one cell type only, with polygonal cells with round nuclei, no (or limited) cytologic atypia, low mitotic activity, and prominent neutrophilic infiltrate. One patient had slightly more infiltrative bone invasion, another lymphovascular, perineural, and skeletal muscle invasion, and a third nodal metastasis after 17 years. By comparison, IPs had bland cytology, neutrophilic microabscesses, mixed immature squamous, goblet cell, and respiratory epithelium, and extremely low mitotic activity. Nonkeratinizing SCCs had basaloid-appearing cells with nuclear pleomorphism, brisk mitotic activity, and apoptosis. All LGPSC were p63 positive. Mitotic activity and Ki67 indices were significantly higher for LGPSCs than IPs and significantly lower than NKSCCs, while p53 immunohistochemistry in LGPSC was identical to nonkeratinizing SCC and higher than for IP. Sequencing showed all five tumors to harbor a MUC6 mutation, one tumor to harbor CDKN2A and PIK3R1 mutations, and one tumor to harbor a NOTCH1 mutation. All LGPSC lacked EGFR and KRAS mutations and lacked copy number variations of any main cancer genes. At a median follow up of 12 months, two LGPSC recurred locally, and one patient died after massive local recurrences and nodal metastases. LGPSC is a distinct, de novo sinonasal carcinoma that can be differentiated from papillomas by morphology and selected immunohistochemistry.

Utility and Practicality of Multi-level Sectioning and Upfront Unstained Slide Cutting in Head and Neck Biopsies: A Critical Analysis.

Upfront interval sectioning (cutting unstained slides between H&E levels) is used at our institution for biopsies at all sites except the gastrointestinal tract. Very limited data exists in the literature for the need for interval sectioning, and we are aware of no data at all for the head and neck. Biopsies from the larynx, oral cavity, pharynx, and sinonasal tract at our institution have had 5 levels cut. Levels 1, 3, and 5 or levels 2 and 5 had been stained with hematoxylin and eosin (H&E), depending on the subsite, and the remaining slides saved for possible later use. We retrospectively evaluated the use of unstained slides at these sites for clinical utility and efficiency by analyzing 3 years of cases from 1/1/2014 to 12/30/2016. A cutoff of 10% utilization was considered justification for continued upfront unstained slide cutting. We collected 706 larynx, 572 oral cavity, 184 pharynx, and 85 sinonasal tract biopsies over 3 years. The overall rate of unstained slide usage was 18.2%. Usage rates were significantly different by site: 7.8% (55/706) for larynx, 21.9% (125/572) for oral cavity, 30.6% (26/85) for sinonasal tract and 40.8% (75/184) for pharynx (p < 0.0001). The most common stain ordered in the pharynx was p16 immunohistochemistry (59.7%), but it was Grocott methenamine silver staining in the larynx (74.5%), oral cavity (70.4%), and sinonasal tract (35.1%). Usage of unstained slides was lowest for the larynx, and review of the biopsies with unstained slides utilized showed that the lesion was present on the 3rd H&E level in all cases. Removing this practice would have translated to saving 1,378 unstained slides. Upfront interval sectioning makes practical sense for biopsies from most sites in the head and neck, especially the pharynx, but our data suggests it can reasonably be forgone at least for biopsies of the larynx.

Low-grade fibromyxoid sarcoma of acral sites: Case report and literature review.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue sarcoma that usually presents as a deep-seated tumor in young adults; however, they can occur on superficial sites, mostly documented in pediatric age groups. LGFMS presenting on acral sites is not highly emphasized in the general pathology or dermatopathology literature. The case presented is that of a 30-year-old man with a foot mass that was removed 15 years earlier and subsequently recurred as two masses, the first occurring between the third and fourth toes/metatarsal region and the second over the lateral tarsal region. An excisional biopsy showed a relatively circumscribed, bland spindle cell proliferation with hypocellular and hypercellular zones. The cells showed minimal pleomorphism and lacked mitotic activity. Immunohistochemical analysis showed immunoreactivity for MUC4 and break-apart fluorescence in situ hybridization was positive for FUS rearrangement, confirming the diagnosis of LGFMS. There are multiple spindle cell tumors that occur on acral sites which usually generates a list of differential diagnoses; however, LGFMS is not usually discussed in that anatomic location. Awareness of the occurrence of LGFMS on acral sites is important to avoid misdiagnosis of this deceptively benign-appearing tumor.