Impact of Cutaneous Squamous Cell Carcinoma Histologic Features on Percent Interrater Agreement Regarding Tumor Differentiation.

BACKGROUND: Poor differentiation predicts adverse outcomes in cutaneous squamous cell carcinoma (CSCC), but there is no standardized, reliable grading system. OBJECTIVE: To explore which histologic features have the greatest impact on CSCC differentiation interrater agreement. MATERIALS AND METHODS: In a prior study, 40 raters graded differentiation for 45 squamous cell carcinomas, and percent interrater agreements were calculated. Cases graded as well/moderately differentiated with 100% agreement (10), those graded as poorly differentiated with ≥80% agreement (5), and those that received a variety of grades with ≤60% agreement (7) were pulled for the current study. Three raters graded individual histologic features for each case, and percent interrater agreements were calculated using both the well/moderately/poorly differentiated grading system and a dichotomized system. RESULTS: The percent interrater agreements were 34.8% for mitoses, 53% for pleomorphism, 59.1% for keratinization, 66.7% for cellular cohesion/intercellular bridges, and 78.8% for tumor edges. Percent agreements improved with dichotomous grading; the largest improvement was seen within the group of cases that had been graded as well/moderately differentiated with 100% agreement in the prior study. CONCLUSION: Future squamous cell carcinoma differentiation grading systems would benefit from eliminating mitotic rate, clearly defining how to grade other features, and dichotomous grading.

Selective Immunoreactivity for WT1 Carboxy-Terminus Distinguishes Desmoplastic Small Round Cell Tumor From its Histologic Mimics.

Desmoplastic small round cell tumor (DSRCT) is an aggressive pediatric round cell sarcoma containing a characteristic EWSR1-WT1 gene fusion. In the absence of genetic data, distinguishing DSRCT from other small round cell tumors of childhood can be problematic due to overlapping histologic and immunohistochemical features. We studied the utility of immunohistochemistry with antibodies targeting both the amino-terminal and carboxy-terminal regions of the Wilms tumor-1 (WT1) protein in differentiating these groups of tumors. The study cohort included 33 cases of genetically confirmed pediatric round cell tumors (10 DSRCTs, 12 Wilms tumors, 10 Ewing sarcomas, and 1 CIC-rearranged sarcoma). Immunoreactivities and immunolocalization of both the WT1 amino-terminus and carboxy-terminus were scored and documented. All DSRCTs displayed selective reactivity for only the WT1 carboxy-terminus (10/10), while dual immunoreactivity for both the WT1 carboxy-terminus (12/12) and amino-terminus antibodies (12/12) were characteristic of Wilms tumors. CIC-rearranged sarcoma showed variable WT1 nuclear immunopositivity (1/1, 1/1) and Ewing sarcomas were consistently WT1-negative for both the WT1 amino-terminus (0/10) and carboxy-terminus (0/10). Dual WT1 amino-terminus and carboxy-terminus immunohistochemistry remains a helpful diagnostic tool in discriminating intraabdominal small round cell tumors, which serves as an adjunct to the genetic information in preventing misdiagnosis.

Urachal mucinous cystic tumor of low malignant potential in a polymorbid female: a case report and review of the literature.

Neoplasms of the urachus are exceedingly rare, representing 0.17% of all bladder cancers. The mucinous cystic tumor of low malignant potential (MCTLMP) subtype is particularly rare with just 25 previous cases reported in the literature. Although rare, MCTLMPs are important to identify due to potential devastating complications and good cure rates with surgical removal. We present a 43 year old female with a nuanced constellation of comorbidities and confirmed MCTLMP following a workup for abdominal pain and irritative lower urinary tract symptoms. Notably, this tumor did not change in size over a 3-year course of serial imaging prior to surgical excision. This urachal MCTLMP represents roughly the 26th and one of the smallest of its subtype reported in the literature. This case illustrates the diagnosis and management of this rare urachal MCTLMP. Individual patient medical history, clinical considerations, and neoplasm characteristics are examined. Although rare, the potential for increased malignancy and potential complications necessitates surgical management and further investigation by the academic community.

Anogenital syringocystadenocarcinoma papilliferum in situ or anaplastic extramammary Paget disease? A unifying concept and review of the literature.

Extramammary Paget disease (EMPD) is a rare cutaneous malignancy that typically involves the genital skin and can be primary or associated with an underlying internal malignancy. The typical histopathological appearance of EMPD consists of single or small aggregates of cells with abundant pale cytoplasm and large pleomorphic nuclei, known as Paget cells, scattered throughout the epidermis. We report a case of anogenital EMPD occurring in a 53-year-old man with unusual histopathologic findings of marked epidermal acanthosis, acantholysis, intraepidermal glandular differentiation, and prominent plasma cell-rich fibrovascular cores. These features were entirely confined to the epidermis and adnexa with no evidence of dermal invasion or underlying systemic disease. We review and summarize the literature for atypical features noted in EMPD and summarize similar findings previously described under a variety of descriptions including anaplastic EMPD, anogenital syringocystadenocarcinoma papilliferum in situ (SCACPIS), SCACPIS-like changes in EMPD, and EMPD mimicking acantholytic squamous cell carcinoma in situ. We propose that these features represent a single entity and be considered under a unifying diagnosis to facilitate recognition of this entity.

Factors Influencing Poor Outcomes in Synthetic Tissue-Engineered Tracheal Replacement.

OBJECTIVES: Humans receiving tissue-engineered tracheal grafts have experienced poor outcomes ultimately resulting in death or the need for graft explantation. We assessed the performance of the synthetic scaffolds used in humans with an ovine model of orthotopic tracheal replacement, applying standard postsurgical surveillance and interventions to define the factors that contributed to the complications seen at the bedside. STUDY DESIGN: Large animal model. SETTING: Pediatric academic research institute. SUBJECTS AND METHODS: Human scaffolds were manufactured with an electrospun blend of polyethylene terephthalate and polyurethane reinforced with polycarbonate rings. They were seeded with autologous bone marrow-derived mononuclear cells and implanted in sheep. Animals were evaluated with routine bronchoscopy and fluoroscopy. Endoscopic dilation and stenting were performed to manage graft stenosis for up to a 4-month time point. Grafts and adjacent native airway were sectioned and evaluated with histology and immunohistochemistry. RESULTS: All animals had signs of graft stenosis. Three of 5 animals (60%) designated for long-term surveillance survived until the 4-month time point. Graft dilation and stent placement resolved respiratory symptoms and prolonged survival. Necropsy demonstrated evidence of infection and graft encapsulation. Granulation tissue with signs of neovascularization was seen at the anastomoses, but epithelialization was never observed. Acute and chronic inflammation of the native airway epithelium was observed at all time points. Architectural changes of the scaffold included posterior wall infolding and scaffold delamination. CONCLUSIONS: In our ovine model, clinically applied synthetic tissue-engineered tracheas demonstrated infectious, inflammatory, and mechanical failures with a lack of epithelialization and neovascularization.

Erdheim Chester disease in a patient with Burkitt lymphoma: a case report and review of literature.

BACKGROUND: Erdheim Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis characterized by widespread tissue infiltration by CD68-positive, CD1a-negative foamy histiocytes. ECD can be difficult to identify, and diagnosis relies on the presence of histiocytes with certain histologic and immunophenotypic features in an appropriate clinical and radiologic setting. Clinical signs and symptoms are variable depending on which organ systems are involved. Most patients have at least skeletal involvement with bone pain as well as fatigue. Other common manifestations include diabetes insipidus, cardiac, periaortic, or retro-orbital infiltration/fibrosis, kidney impairment, xanthelasmas, among others. CASE PRESENTATION: Herein, we describe a case of BRAF-mutation positive ECD in a patient with Burkitt lymphoma, and we review recent literature. CONCLUSION: Underlying BRAF and other MAPK pathway mutations are identified in approximately 50% of cases of ECD, which aids in diagnosis as well as enables novel targeted treatments. ECD patients have an increased risk of myeloid neoplasms; however, unlike other histiocytoses, an association with lymphoproliferative disorders has not been recognized.

Diagnosing clear cell neuroendocrine tumors on cytological specimens: Report of two cases and brief literature review.

Although many of the common manifestations of Von Hippel-Lindau (VHL) disease are relatively well known, there is one particular entity which is quite rare, but which appears to show a specific predilection for VHL patients. This entity is clear cell neuroendocrine tumor (NET). It is a difficult diagnosis to make due to its cytomorphologic similarities to other entities, such as metastatic clear cell renal cell carcinoma and paraganglioma, amongst others. These tumors, however, are characteristically positive for neuroendocrine markers such as synaptophysin and chromogranin, as well as cytokeratins. Emerging evidence also suggests that clear cell NETs in VHL patients are specifically positive for inhibin, when compared to their counterparts in non-VHL patients, which may assist in the diagnosis in as yet undiagnosed patients with VHL disease. Herein, we present two cases of inhibin-positive clear cell NETs, one in a VHL patient, and the other in a non-VHL patient. These cases propose a potential warning to those relying on inhibin positivity to incite an expedition down a rabbit hole for a diagnosis of VHL. Diagn. Cytopathol. 2017;45:757-760. © 2017 Wiley Periodicals, Inc.

Corpora amylacea and molluscum contagiosum on a cervical pap smear.

When evaluating a Papanicolaou (Pap) smear, the cytology of the squamous epithelial cells is of utmost importance. This is what cytopathologists use to render a diagnosis, ranging from normal to atypical squamous cells of undetermined significance (ASCUS) to high grade squamous intraepithelial lesions, or even squamous cell carcinoma. However, occasionally the pathologist will run into microscopic noncellular material as in our case, such as corpora amylacea on the slides, or even uncommon viral inclusions such as Molluscum contagiosum (MCV). When these less common entities make their way on to a cervical Pap smear, it is important not only to correctly recognize them, but to understand their clinical implications as well. Diagn. Cytopathol. 2017;45:179-181. © 2016 Wiley Periodicals, Inc.