Novel autopsy and genetic findings in an acardiac twin: case report and literature review.

Twin reversed arterial perfusion (TRAP) sequence is a rare complication of monochorionic twinning whereby a donor twin perfuses an acardiac twin via aberrant vascular anastomoses. The resulting paradoxical retrograde blood flow supplying the acardiac twin is oxygen-poor, leading to some of the most severe malformations encountered in humans. Though the first descriptions of acardiac twins date back to at least the 16th century, the pathophysiologic processes which underpin the development of TRAP sequence are still being elucidated. Theories on the pathogenesis of TRAP sequence include deficiencies intrinsic to the embryo and primary abnormalities of the placental vasculature. Autopsy studies continue to provide clues to the underlying pathogenesis of TRAP sequence, and the characterization of the spectrum of manifestations that can be observed in acardiac twins. Herein, we present the clinical, autopsy, and molecular findings in a unique case of TRAP sequence. Novel findings include a primitive cloaca-like structure and chromosomal aberrations involving 6q11.1 and 15q25.1.

Novel autopsy and genetic findings in an acardiac twin: case report and literature review

ABSTRACT Twin reversed arterial perfusion (TRAP) sequence is a rare complication of monochorionic twinning whereby a donor twin perfuses an acardiac twin via aberrant vascular anastomoses. The resulting paradoxical retrograde blood flow supplying the acardiac twin is oxygen-poor, leading to some of the most severe malformations encountered in humans. Though the first descriptions of acardiac twins date back to at least the 16th century, the pathophysiologic processes which underpin the development of TRAP sequence are still being elucidated. Theories on the pathogenesis of TRAP sequence include deficiencies intrinsic to the embryo and primary abnormalities of the placental vasculature. Autopsy studies continue to provide clues to the underlying pathogenesis of TRAP sequence, and the characterization of the spectrum of manifestations that can be observed in acardiac twins. Herein, we present the clinical, autopsy, and molecular findings in a unique case of TRAP sequence. Novel findings include a primitive cloaca-like structure and chromosomal aberrations involving 6q11.1 and 15q25.1.

Comparative study of two reprocessing methods for formalin fixed paraffin embedded tissue.

Formalin fixed paraffin embedded tissue occasionally requires reprocessing if the histologic quality of a section is inadequate for clinical diagnosis. The Pat Dry (PD) and the Serial Xylene (SX) methods are two techniques described in the literature to reprocess under-fixed and/or under-processed tissue samples. To date, no study has compared the effects of these methods on the histologic quality of tissue sections, cost, and turnaround times. In the present study, these two methods were evaluated on 129 tissue samples taken from 40 submitted clinical specimens, 3 blocks per sampled location. Before processing, sample Group 1 (Control) was cut at routine 3-5 mm thickness. Sample Groups 2 and 3 were cut at 10 mm to ensure the thicker tissues would be poorly processed. Histotechnicians performed a subjective evaluation of all the samples at the time of embedding and microtomy. Hematoxylin and eosin stained sections from all samples were scored for histologic quality by two pathology residents. Thicker samples (Groups 2 and 3) were then reprocessed using either PD or SX methods, re-sectioned, stained, and then re-scored by the pathology residents. The two reprocessing methods equally improved quality scores and reduced the fraction of slides that were rejected. The PD method average preparation time was 66 minutes as compared to 250 minutes for the SX method. The PD method was easier to perform than the SX method, required less reagent, and was less susceptible to reagent spillage than the SX method.

Fatal tumor lysis syndrome in a patient with metastatic gastric adenocarcinoma.

Tumor lysis syndrome is a well-characterized and potentially deadly complication of spontaneous or treatment-related tumor destruction, and it is most commonly associated with hematologic malignancies. Our case illustrates a rare example of fatal tumor lysis syndrome in the setting of metastatic gastric adenocarcinoma treated with radiation therapy. This case highlights the critical importance of identifying patients with solid organ malignancies at risk for tumor lysis syndrome and of early recognition and treatment of this syndrome.

Encapsulated papillary carcinoma with and without frank invasion: Comparison of clinicopathologic features and role of axillary staging.

To investigate clinical and pathologic features of encapsulated papillary carcinomas (EPCs) that may be associated with invasive disease and characterize the axillary staging practices for EPCs at our institution. A pathology database search for cases containing "papillary carcinoma" was performed. Slides were reviewed by two pathologists. Clinicopathological features and axillary staging practices of EPCs with and without invasion were compared. Twenty-five cases of EPCs were identified. Fifteen cases contained a frank invasive tumor (60%), which were all pT1 (0.7 ± 0.56 cm), and the majority were ER-positive, HER2-negative, low-grade IDC-NST. Seventeen patients underwent sentinel lymph node biopsies (SLNB). No nodal metastases were identified. Follow-up was available for 24 patients (mean = 39 ± 29 months); 23 had no NED. Patients that presented with a self-palpated mass (versus screening) were more likely to have an invasive component; however, no pathologic or radiologic features differentiated EPCs with and without frank invasion. Pathologic and radiologic characteristics did not differentiate EPCs with and without frank invasion. EPCs have an excellent prognosis supported by the notable disease-free survival and negative nodal status in our cohort, which supports the notion that patients with EPCs may forgo axillary staging.

Fatal tumor lysis syndrome in a patient with metastatic gastric adenocarcinoma

Tumor lysis syndrome is a well-characterized and potentially deadly complication of spontaneous or treatment-related tumor destruction, and it is most commonly associated with hematologic malignancies. Our case illustrates a rare example of fatal tumor lysis syndrome in the setting of metastatic gastric adenocarcinoma treated with radiation therapy. This case highlights the critical importance of identifying patients with solid organ malignancies at risk for tumor lysis syndrome and of early recognition and treatment of this syndrome.

Melanocytic aggregates with unique morphology associated with regression of basal cell carcinoma.

BACKGROUND: Spontaneous regression of basal cell carcinomas (BCC) is a well-documented phenomenon. In practice, we have observed melanocytic aggregates associated with BCC at various stages of regression showing unique morphologic features. METHODS: Fourteen cases featuring melanocytic aggregates were retrospectively identified through a pathology database search. Clinical and histopathologic features were systematically evaluated, and additional immunohistochemical studies were performed. Melanocyte density within tumor nodules was compared to a group of control BCCs. RESULTS: All cases showed BCC at various stages of regression with associated melanocytic aggregates, as highlighted by Melan-A and SOX10 immunostains. Three of 14 cases (21.4%) had only dermal melanocytic nests, while 11 (78.6%) had both junctional and dermal nests. The melanocytic aggregates all had similar asymmetrical architecture and lacked maturation. The melanocytes were small, uniform, bland, and had minimal cytoplasm. Their nuclei were overlapping and hyperchromatic, and had inconspicuous nucleoli. None of the melanocytic aggregates stained for BRAFV600E by immunohistochemistry. No patient developed a recurrent or metastatic melanocytic lesion (median follow-up 42 months). Melanocyte density was higher in the case series than in the control BCCs (P = 0.0008). CONCLUSION: We described the unique morphology of melanocytic aggregates associated with BCC regression.

Fine needle aspiration of malignant melanoma with myxoid features: A case report with molecular analysis.

Malignant melanoma with myxoid features (MMM) is a rare melanoma variant in which tumor cells are embedded within a basophilic myxoid stroma. The stromal matrix is composed of acidic mucopolysaccharides, which are thought to be produced by mesenchymal stromal cells in response to melanoma invasion. Interestingly, this myxoid matrix is more often seen in metastasis from a primary tumor that does not have a myxoid stroma. The diagnosis of MMM on fine needle aspiration (FNA) can be confused with other myxoid tumors. Herein, we present a case of MMM diagnosed by FNA of a peri-auricular lymph node in an 89-year-old man with a history of resected malignant melanoma. We describe the clinical, cytohistological, and immunohistochemical findings, and present the unique molecular alterations that were identified. We also discuss the differential diagnosis and potential diagnostic pitfalls associated with MMM.

Diagnostic and prognostic value of glucose transporters in melanocytic lesions.

We have previously reported increased glucose transporter 1 (GLUT1) expression in melanoma compared to benign nevi, associated with a significantly lower survival rate. GLUT1 upregulation was highly specific for distinguishing melanoma from benign nevi, yet poorly sensitive, likely because of expression of other GLUT isoforms. The purpose of this study was to evaluate GLUT2 and GLUT3, as melanoma biomarkers. A tissue microarray, consisting of 91 primary melanomas, 18 melanoma metastases, and 56 nevi, was examined using GLUT2 and GLUT3 immunohistochemistry. A semiquantitative scoring method was used to determine the percentage of positive tumor cells and staining intensity. GLUT2 was negative in all melanomas and benign nevi examined. Increased GLUT3 expression was more frequent in melanoma than in nevi (P < 0.0001), and in metastatic melanoma than in primary melanomas (P < 0.001). Of melanoma cases, 85.3% expressed either GLUT1 or GLUT3 or both, 39.4% of melanoma cases coexpressed GLUT1 and GLUT3, 17.4% of melanoma cases only expressed GLUT1, 28.4% of melanoma cases only expressed GLUT3, and 14.7% of melanoma cases were negative for both markers. Patients whose melanoma exhibited a high level of GLUT3 had significantly lower survival rates than those with low GLUT3 expression (P = 0.002). Evaluating both GLUT1 and GLUT3 increased the diagnostic value by increasing the sensitivity while the specificity remained high. In conclusion, GLUT2 was not expressed in melanocytes. GLUT3 expression was upregulated in melanoma compared with nevi, especially in those with worse prognosis. Similar to GLUT1, GLUT3 may serve as a useful diagnostic and prognostic marker.

Epithelioid Fibrous Histiocytoma: A Concise Review.

Epithelioid fibrous histiocytoma (EFH) is a rare lesion believed to arise from dermal microvascular unit fibroblasts and dendritic histiocytes. EFH has long been considered a morphologic variant of benign fibrous histiocytoma (dermatofibroma), with prominent epithelioid cytomorphology that can mimic both vascular and melanocytic neoplasms. The molecular basis for the relationship between EFH and benign fibrous histiocytoma has remained largely unknown, with some authors suggesting that EFH represents an entity that is biologically distinct from benign fibrous histiocytoma. Recent molecular studies have identified the presence of recurrent anaplastic lymphoma kinase (ALK) gene rearrangements, a phenomenon that has not been described in benign fibrous histiocytoma. These new molecular findings highlight the uniqueness of this rare tumor and may prove useful as a diagnostic tool for differentiation from other histologic mimics.