Shefali Chopra

Contemporary Management of Retroperitoneal Soft Tissue Sarcomas

Management of retroperitoneal soft tissue sarcomas (RP STS) can be very challenging. In contrast to the more common extremity STS, the two predominant histologic subtypes encountered in the retroperitoneum are well-differentiated/dedifferentiated liposarcoma and leiomyosarcoma. Surgery remains the mainstay of treatment for RP STS. Preoperative planning and anticipation of the need for resection of adjacent organs/structures are critical. The extent of surgery, including the role of compartmental resection, is still controversial. Radiation therapy may be an important adjunct to surgery to provide locoregional disease control; this is currently being evaluated in the preoperative setting in the EORTC STRASS trial. Systemic therapy, tailored to the specific histologic subtype, may also be of benefit for the management of RP STS. Further investigation of novel therapies (e.g., targeted therapies, immunotherapy) is needed. Overall, multi-institutional collaboration is important moving forward, to continue to better understand and optimize management of this disease.

Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation

Metastatic neuroendocrine neoplasms to the breast may show considerable morphologic overlap with primary mammary carcinomas, particularly those showing evidence of neuroendocrine differentiation, and may be misdiagnosed as such. Accurate distinction between these two entities is crucial for determination of appropriate clinical management. The histologic and immunohistochemical features of metastatic neuroendocrine neoplasms to the breast were studied and compared with the features of primary invasive mammary carcinomas with neuroendocrine differentiation, which served as controls. Of the metastatic neuroendocrine neoplasms, 15 were well-differentiated neuroendocrine tumors with carcinoid tumor-type morphology and 7 were poorly differentiated/high-grade neuroendocrine carcinomas with small-cell or large-cell neuroendocrine carcinoma morphology. The majority of the metastatic neoplasms originated in the lung and gastrointestinal tract. There were histologic similarities between metastatic neuroendocrine neoplasms and invasive mammary carcinomas with neuroendocrine differentiation, both of which exhibited neuroendocrine histologic features (nested and trabecular architecture, minimal tubular differentiation, and characteristic nuclear features). Only one case of the invasive mammary carcinomas with neuroendocrine differentiation was modified Bloom-Richardson grade 1 (largely due to minimal tubular differentiation on most such tumors), and the invasive mammary carcinomas with neuroendocrine differentiation were often associated with in situ carcinoma. Immunohistochemistry was helpful in distinguishing metastatic neuroendocrine neoplasms from invasive mammary carcinomas with neuroendocrine differentiation. Whereas the majority of invasive mammary carcinomas with neuroendocrine differentiation were positive for estrogen receptor and GATA3, metastatic neuroendocrine neoplasms were typically negative for estrogen receptor and GATA3, and metastatic well-differentiated neuroendocrine tumors often showed immunoreactivity for site-specific markers. Although the histologic and immunohistochemical features of a breast tumor may raise the suspicion of a metastatic neuroendocrine neoplasm, the pathologic findings should be interpreted in the context of the clinical history and imaging findings in order to establish an accurate diagnosis.

The role of margins in extremity soft tissue sarcoma.

For extremity soft tissue sarcomas, limb salvage is now standard of care. The extent of surgical margins is balanced with functionality of the resected limb. Although negative margins are the goal, the necessary width is unclear. Additional considerations for margin adequacy include presence of anatomic barriers such as fascia and periosteum, proximity of critical structures, receipt of adjuvant and neoadjuvant therapies, and histologic subtype. Multidisciplinary team discussion is critical for treatment planning. J. Surg. Oncol. 2016;113:333–338.

Impact of margin status and lymphadenectomy on clinical outcomes in resected pancreatic adenocarcinoma: implications for adjuvant radiotherapy

BACKGROUND Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the clinical significance of margin clearance distance and lymph node (LN) parameters, such as extent of dissection and LN ratio. We assessed the impact of these variables on clinical outcomes to more clearly define the subset of patients who may benefit from adjuvant radiotherapy (RT). METHODS We identified 106 patients with resected stage 1-3 PDA from 2007-2013. Resection margins were categorized as positive (tumor at ink), ≤1, or >1 mm. LN evaluation included total number examined (NE), number of positive nodes (NP), ratio of NP to NE (NR), extent of dissection, and positive periportal LNs. The impact of these variables was assessed on disease-free survival (DFS) and overall survival (OS) using multivariate cox proportional hazards modeling. RESULTS In patients receiving adjuvant chemotherapy (CT) alone, greater margin clearance led to improved DFS (P=0.0412, HR =0.51). Range of NE was 4-37, with a mean of 19. NE was not associated with DFS or OS, yet absolute NP of 5 or more was associated with a significantly worse DFS (P=0.005). Whereas periportal lymphadenectomy did not result in improved DFS or OS, patients with positive periportal LN had worse clinical outcomes (DFS, P=0.0052; OS, P=0.023). The use of adjuvant CRT was associated with improved OS (P=0.049; HR=0.29). CONCLUSIONS In patients receiving adjuvant CT alone, there was a clinically significant benefit to clearing the surgical margin beyond tumor at ink. Having ≥5 NP and positive periportal LN led to significantly worse clinical outcomes. The addition of adjuvant RT to CT in resected PDA improved OS. A comprehensive evaluation of resection margin distance and LN parameters may identify more patients at risk for locoregional failure who may benefit from adjuvant CRT.

Comprehensive evaluation of colorectal polyps in specimens from endoscopic biopsies.

Modern evaluation of specimens from biopsies of colorectal polyps has become increasingly complex because of tremendous progress in the understanding of colorectal neoplasia. Although pathologists are generally familiar with the basic handling of carcinoma in the setting of polypectomies or resections, the comprehensive evaluation of specimens from biopsies of colorectal polyps obtained with forceps is far from intuitive and has yet to be reviewed. Comprehensive evaluation requires always addressing several key issues, even when dealing with seemingly routine cases. These issues include taking further action when initial sections lack polyps, accurately quantitating polyps, accurately classifying polyps, determining whether thresholds are met for considering conditions at high risk for carcinoma, detecting incidental findings other than polyps, and determining which incidental findings are clinically significant. In particular, polyposis with attenuated phenotype or Lynch syndrome may be clinically occult, and the possibility of these entities should always be kept in mind, regardless of age or history. Ancillary studies performed immediately on carcinoma that is detected at biopsy guides surgery, guides medical therapy, prognosticates, provides evidence for hereditary neoplasia, and guides surveillant colonoscopy for the family.

Specimens from biopsies of colorectal polyps often harbor additional diagnoses.

Objectives. The utility of examining specimens from colorectal biopsies of polyps for nonneoplastic diseases is currently unknown. Our objectives were to characterize such additional diagnoses that could be rendered. Methods. We retrospectively and prospectively reviewed specimens from endoscopic biopsies of colorectal polyps obtained during routine screening or surveillance. Results. 17 of 168 specimens (10.1%) contained additional diagnoses, including schistosomiasis, eosinophilic colitis, intestinal spirochetosis, melanosis coli, and other entities. These findings were easily overlooked because they often affected mucosa that was spared by the polyps or were often evident only at high magnification. Schistosomiasis, eosinophilic colitis, and intestinal spirochetosis were clinically occult. Conclusions. Specimens from biopsies of colorectal polyps often harbor other diagnoses, in addition to polyps, and can be simultaneously screened for polyps and examined for nonneoplastic diseases. Detection of other diagnoses in addition to polyps requires awareness, examination at high magnification, and examination of areas spared by the polyps.

Cytologic Diagnosis of Chordoma in a Peritoneal Effusion

BACKGROUND Chordoma, a distinct malignant neoplasm arising from the remnants of the notochord, occurs mostly in patients in the fifth to seventh decade of life. Metastasis occurs in 20-30% of cases. The most common metastatic sites are lungs and, less commonly, other bones and visceral organs. The cytologic features of chordoma in both primary and metastatic foci have been described for specimens obtained by fine needle aspiration biopsy. A few cases have been reported in the sputum and the cerebrospinal fluid. CASE A 57-year-old man presented with metastatic chordoma diagnosed in a peritoneal effusion. Cytospin slides of the effusion showed numerous individual and clusters of polygonal, round epithelial cells with a background of myxoid chondroid substance, which stained metachromatic on Diff-Quik slides. Many diagnostic physaliphorous cells were present and characterized by abundant intracytoplasmic vacuoles of various sizes. The nuclei were monotonous, with minimal anisonucleosis. The nuclei had evenly dispersed chromatin with occasional small, eosinophilic nucleoli. The nuclear membranes were smooth, with focal indentation. The differential diagnosis included an adenocarcinoma and metastatic chordoma. Immunohistochemistry applied to the cell block showed that the neoplastic cells were positive for cytokeratin and S-100 protein. CONCLUSION The clinical history with immunohistochemical profiles helped confirm the diagnosis of metastatic chordoma.

Drug-Induced Liver Injury—Perspectives from Pathology

Purpose of ReviewDrug-induced liver injury (DILI) may be caused by prescription or over-the-counter medications, herbals and nutritional supplements, or environmental agents. This review provides an overview of (1) pathogenetic mechanisms and risk factors, (2) biochemical classification, (3) diagnostic approach, (4) role of liver biopsy, and (5) narratives on commoner agents that cause DILI.Recent FindingsDILI is increasingly seen in contemporary practice due to increased usage of medications in general, introduction of newer agents for treatment of cancers and autoimmune diseases, and increasing consumption of herbals and nutritional supplements.SummaryDrug-induced liver injury is a significant cause of liver disease worldwide. No clinical, biochemical, or histological feature is specific for the diagnosis of DILI, which can mimic every pattern of liver injury and is in the differential diagnosis of every patient with liver disease. The diagnosis of DILI relies on (1) establishing a temporal association between clinical disease and initiation of the suspected drug, followed in the majority of cases by clinical improvement and disease resolution on its withdrawal and (2) exclusion of competing causes of liver injury. Herbals and nutritional supplements are particularly interesting as these are generally regarded as “safe, natural” compounds by an increasingly health-conscious population. Establishing a temporal relationship is often challenging as the patient may be taking multiple supplements simultaneously and is usually unclear about timing of initiation and withdrawal of the agents. Additionally, these agents change in potency and composition depending on the harvest conditions of the constituent botanicals.

Solid aneurysmal bone cyst of the humerus mimics metastasis or brown tumor

Solid aneurysmal bone cyst (ABC) is a rare subtype of ABC that most commonly involves the small bones of the hands or feet. We present a case of a solid ABC of the distal humerus in a 52-year-old man with a history of chronic kidney disease and renal cell carcinoma. On imaging with plain radiographs, CT, and MRI, this expansile lucent lesion with solid internal enhancement had an appearance that overlapped with metastasis or brown tumor of hyperparathyroidism. On 18F-FDG PET-CT, this lesion was hypermetabolic with an SUVmax of 9.9. Only 37 cases of solid ABC have previously been reported to involve the long bones in the literature, and only 4 in the humerus. We review the clinical, imaging, and histopathological findings and differential diagnosis of solid ABC, and highlight the usefulness of identifying the USP6 gene rearrangement on FISH to distinguish this lesion from other lesions with secondary ABC formation.

Second Primary Malignancies in Patients with Well-differentiated/Dedifferentiated Liposarcoma

Background: Well-differentiated/dedifferentiated (WD/DD) liposarcoma is a rare malignancy of putative adipocyte origin. To our knowledge, there have only been isolated case reports describing second primary cancer in patients with this disease. We report on a combined case series of such patients and explore the frequency of this occurrence using a national cancer database. Materials and Methods: Demographics and clinicopathological data were collected from patients with WD/DD liposarcoma who were found to have a concurrent or subsequent second primary cancer, at one of three sarcoma referral centers from 2014-2016. The Surveillance, Epidemiology and End Results (SEER) database was also queried to identify adult patients diagnosed with WD/DD liposarcoma between 1973-2012. Observed/expected (O/E) ratios of second primary malignancies among these cases were calculated by comparison to the age-adjusted cancer incidence in the general population using SEER*stat software. Results: In total, 26 out of 312 consecutive patients (8.3%) with WD/DD liposarcoma at our centers had a second primary cancer identified within 2 years of liposarcoma diagnosis. In the SEER database, among 1,845 patients with WD/DD liposarcoma, 75 (4.1%) had a second cancer within 2 years after liposarcoma diagnosis (O/E ratio=1.81, 99% confidence interval(CI)=1.33-2.40). Patients less than 50 years old at the time of liposarcoma diagnosis had a higher O/E ratio for second primary malignancy compared to older patients. A total of 269 patients (14.6%) developed a second cancer (O/E=1.33, 99% CI=1.15-1.54). Conclusion: In some patients with WD/DD liposarcoma, there appears to be an increased risk of having a second primary cancer. Further validation and investigation is needed, as this finding may have implications (e.g. closer screening) for patients with this disease.