The utility of a myeloid mutation panel for the diagnosis of myelodysplastic syndrome and myelodysplastic/myeloproliferative neoplasm.

INTRODUCTION: The diagnosis of myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) is based on morphology and cytogenetics/FISH findings per 2017 WHO classification. With rare exceptions, somatic mutations have not been incorporated as the diagnostic criteria. METHODS: We analyzed the utility of mutational analysis with a targeted 54-gene or 40-gene next-generation sequencing (NGS) panel in the diagnosis of MDS and MDS/MPN. RESULTS: We retrospectively collected 92 patients who presented with unexplained cytopenia with or without cytosis, including 32 low-grade MDS (MDS-L), 18 high-grade MDS (MDS-H), 5 therapy-related MDS (MDS-TR), 19 MDS/MPN, and 18 negative cases. Of 92 patients, 197 somatic mutations involving 38 genes were detected and had variant allele frequency (VAF) ranging from 3% to 99%. The most common mutated genes were TET2, ASXL1, RUNX1, TP53, SRSF2, and SF3B1. MDS-L, MDS-H, MDS-TR, and MDS/MPN showed an average number of somatic mutations with a mean VAF of 1.9/33%, 2.6/30%, 2/36%, and 4/41%, respectively. SF3B1 mutations were exclusively observed in MDS-L and MDS/MPN. TP53 gene mutations were more frequently seen in MDS-H and MDS-TR. Among 34 patients with a diagnosis of MDS or MDS/MPN with normal cytogenetics, 31 patients (91%) had at least 1 mutation and 24 patients (71%) had ≥2 mutations with ≥10% VAF. CONCLUSION: A myeloid mutational panel provides additional evidence of clonality besides cytogenetics/FISH studies in the diagnosis of cytopenia with or without cytosis. Two or more mutations with ≥10% VAF highly predicts MDS and MDS/MPN with a positive predictive value of 100%.

Factors affecting the concordance of radiologic and pathologic tumor size in breast carcinoma.

BACKGROUND: Radiologic assessment of tumor size is an integral part of the work-up for breast carcinoma. With improved radiologic equipment, surgical decision relies profoundly upon radiologic/clinical stage. We wanted to see the concordance between radiologic and pathologic tumor size to infer how accurate radiologic/clinical staging is. MATERIALS AND METHODS: The surgical pathology and ultrasonography reports of patients with breast carcinoma were reviewed. Data were collected for 406 cases. Concordance was defined as a size difference within ±2 mm. RESULTS: The difference between radiologic and pathologic tumor size was within ±2 mm in 40.4% cases. The mean radiologic size was 1.73 ± 1.06 cm. The mean pathologic size was 1.84 ± 1.24 cm. A paired t-test showed a significant mean difference between radiologic and pathologic measurements (0.12 ± 1.03 cm, p = 0.03). Despite the size difference, stage classification was the same in 59.9% of cases. Radiologic size overestimated stage in 14.5% of cases and underestimated stage in 25.6% of cases. The concordance rate was significantly higher for tumors ≤2 cm (pT1) (51.1%) as compared to those greater than 2 cm (≥pT2) (19.7%) (p < 0.0001). Significantly more lumpectomy specimens (47.5%) had concordance when compared to mastectomy specimens (29.8%) (p < 0.0001). Invasive ductal carcinoma had better concordance compared to other tumors (p = 0.02). CONCLUSION: Mean pathologic tumor size was significantly different from mean radiologic tumor size. Concordance was in just over 40% of cases and the stage classification was the same in about 60% of cases only. Therefore, surgical decision of lumpectomy versus mastectomy based on radiologic tumor size may not always be accurate.

Dedifferentiated endometrial carcinoma: an ongoing diagnostic dilemma.

Tumours of uterine corpus are the most common gynaecological malignancies. The clinicopathological features of most of these tumours are well understood; however, dedifferentiated endometrial carcinoma still requires a lot of research to establish adequate management guidelines. The entity was first described in 2006 and is an aggressive tumour with poor prognosis. We present two cases of this tumour with a literature review, emphasising morphologic and immunohistochemical features that may help in the differential diagnosis.

Tumor Size in Breast Carcinoma: Gross Measurement Is Important!

INTRODUCTION: The staging of breast carcinoma is mainly dependent on tumor size and lymph node status. Small increments in tumor size upstage the patient. An accurate determination of the tumor size is therefore critically important. Although the final staging is based on microscopic size, pathologists rely on gross measurements in a considerable number of cases. METHODS: We investigated the concordance between gross and microscopic measurements of breast carcinoma as well as factors affecting this concordance. This study is a retrospective review of surgical pathology reports of invasive breast carcinomas. Data were collected for 411 cases. Concordance was defined as a size difference within ±2 mm. RESULTS: Gross and microscopic sizes were identical in 33.1% of cases. Gross and microscopic size difference was within ±2 mm in 56% of cases. Despite the size difference, stage classification ended up being the same in 68.6% of cases. Tumor stage was over estimated by gross measurement in 17.0% of cases and underestimated in 14.4% of cases. The concordance was significantly higher for those tumors in which final pathologic tumor (pT) size was greater than 2 cm (≥pT2) as compared with those less than or equal to 2 cm (≤pT1; P < .0001). A higher proportion of mastectomy specimens (61.4%) were concordant as compared with lumpectomy specimens (52.1%). CONCLUSION: Gross and microscopic tumor sizes were concordant in 56% of cases. Stage classification based on gross and microscopic tumor size was different in nearly one third (31.4%) of cases. Gross tumor size is critically important in accurate staging at least in cases where tumor size cannot be confirmed microscopically.

A novel modality for intraoperative margin assessment and its impact on re-excision rates in breast conserving surgery.

BACKGROUND: A single center retrospective chart review was performed examining the ability of a novel radiofrequency probe (Margin Probe; Dune Medical Devices, Caesarea, Israel) for intraoperative margin assessment to reduce the number of reexcisions in breast-conserving surgery. METHODS: Reexcision rates were evaluated in one-hundred and twenty consecutive patients before and after the institution of the device. Utility of the device was evaluated by comparing intraoperative feedback with postoperative pathology reports. RESULTS: Two hundred and forty patient subjects were reviewed in total. There was a significant decrease in the re-lumpectomy rate (50%, p = 0.039) in the device group without increasing the total volume of tissue resected. CONCLUSIONS: The use of the MarginProbe device as an adjunct to the standard of care resulted in reduction of positive margins after lumpectomy and the number of re-excisions, significantly improving outcomes in breast-conserving surgery at our institution.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells reported in an asymptomatic patient: a rare case and literature review.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UC-OGC) is a rare and poorly described pancreatic malignancy. It is comprised of mononuclear, pleomorphic, and undifferentiated cells as well as osteoclast-like giant cells (OGC's). It constitutes less than 1% of pancreatic non-endocrine neoplasia and is twice as likely to occur in females as in males. Its histopathologic properties remain poorly understood. It is suspected that UC-OGC is of epithelial origin that can then transition to mesenchymal elements. As part of this study, we describe a case of a malignant pancreatic neoplasm that was discovered in a 69-year old patient as an incidental finding. We also provide an overview of previously published data to highlight UC-OGC's clinical and pathologic features.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells reported in an asymptomatic patient: a rare case and literature review

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UC-OGC) is a rare and poorly described pancreatic malignancy. It is comprised of mononuclear, pleomorphic, and undifferentiated cells as well as osteoclast-like giant cells (OGC's). It constitutes less than 1% of pancreatic non-endocrine neoplasia and is twice as likely to occur in females as in males. Its histopathologic properties remain poorly understood. It is suspected that UC-OGC is of epithelial origin that can then transition to mesenchymal elements. As part of this study, we describe a case of a malignant pancreatic neoplasm that was discovered in a 69-year old patient as an incidental finding. We also provide an overview of previously published data to highlight UC-OGC's clinical and pathologic features.

Pulmonary placental transmogrification associated with adenocarcinoma of the lung: a case report with a comprehensive review of the literature.

Pulmonary placental transmogrification (PT) is a rare entity with less than 40 cases reported in the literature. Most reported cases are associated with either bullous emphysema or with pulmonary fibrochondromatous hamartomas. We present only the second case of PT associated with adenocarcinoma of the lung. A 67-year-old female with multiple chronic medical ailments presented with shortness of breath and was found to have a 6-cm mass in the upper lobe of her right lung. A computed tomography (CT) guided core biopsy was performed that showed a well-differentiated adenocarcinoma. Interestingly the normal lung tissue showed placental villous architecture. A unique feature of our case is that the diagnosis was made on a needle core biopsy, unlike all the other cases in the literature. We also provide a comprehensive review of this rare entity.

Pulmonary placental transmogrification associated with adenocarcinoma of the lung: a case report with a comprehensive review of the literature

Pulmonary placental transmogrification (PT) is a rare entity with less than 40 cases reported in the literature. Most reported cases are associated with either bullous emphysema or with pulmonary fibrochondromatous hamartomas. We present only the second case of PT associated with adenocarcinoma of the lung. A 67-year-old female with multiple chronic medical ailments presented with shortness of breath and was found to have a 6-cm mass in the upper lobe of her right lung. A computed tomography (CT) guided core biopsy was performed that showed a well-differentiated adenocarcinoma. Interestingly the normal lung tissue showed placental villous architecture. A unique feature of our case is that the diagnosis was made on a needle core biopsy, unlike all the other cases in the literature. We also provide a comprehensive review of this rare entity.

Cisplatin-Induced Nephrotoxicity and HIV Associated Nephropathy: Mimickers of Myeloma-Like Cast Nephropathy.

Myeloma cast nephropathy is an obstructing disorder of renal tubules, caused by precipitation of Bence Jones proteins. Myeloma-like cast nephropathy (MLCN) has been reported in the literature to occur in various primary renal and nonrenal diseases. We present a series of three rare cases of cast nephropathy, two of which are HIV patients, and the third patient is receiving cisplatin-based chemotherapy. However, in all three patients plasma cell dyscrasia has been ruled out. A 30-year-old male was admitted to the hospital with facial cellulitis. The second patient is a 31-year-old male who presented with Pneumocystis jiroveci pneumonia. The third patient was treated with cisplatin-based chemotherapy for carcinoma. First two cases revealed foci of diffuse tubular dilatation containing hyaline casts and interstitial inflammatory infiltrate, in addition to globally sclerotic glomeruli with ultrastructural foot process fusion and mesangium expansion. The third case showed acute tubular injury and cast formation of irregular casts composed of amorphous or granular material of low density admixed with scattered high electron-dense globules. Myeloma-like cast nephropathy and true myeloma cast nephropathy pose similar destructive effects on renal parenchyma. This new pattern of HIV-related nephropathy should be considered in HIV patients with MLCN, once monoclonal gammopathy is ruled out.

Metastatic prostatic stromal sarcoma: A challenging diagnosis on fine-needle aspiration with broad differential diagnosis.

Prostatic stromal sarcomas (PSS) are rare solid organ mesenchymal sarcomas. PSS may pose difficult diagnostic challenges on fine needle aspiration biopsy. We report a 48-year-old man diagnosed with metastatic high grade prostatic stromal sarcoma by a CT-scan guided fine needle aspiration (FNA) biopsy of a right lower lung lobe nodule. We reviewed the literature on the epidemiologic, cyto-histological, and immunophenotypic findings and discussed the differential diagnosis for this rare entity.

Benign Multicystic Peritoneal Mesothelioma: A Rare Condition in an Uncommon Gender.

Benign Multicystic Peritoneal Mesothelioma (BMPM) is a rare condition that arises from the abdominal peritoneum. Fewer than 200 cases have been reported worldwide. BMPM usually affects premenopausal women and is extremely rare in men. Many factors are suspected to contribute to its development, such as previous surgery, endometriosis, and familial Mediterranean fever. The main management is surgical resection; however, it is estimated that the recurrence rate is up to 50%. Malignant transformation is rare. We report a case series of three male patients who were diagnosed with BMPM and were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

Composite Lymphoma: Opposite Ends of Spectrum Meet.

An 18-year-old African-American female presented with an episode of syncope. Initial investigations revealed large lung mass with invasion into right atrium along with lesions in kidneys and liver. Patient also developed superior vena cava syndrome due to lung mass. Biopsy of lung mass revealed diagnosis of composite lymphoma with involvement by primary mediastinal B-cell lymphoma (PMBCL) and classical Hodgkin lymphoma. Patient was started on dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R) with complete response to treatment. This case represents an extremely rare type of aggressive lymphoma and can guide clinicians in managing such cases since there are no standard guidelines for treatment. To the best of our knowledge, this is the first reported case of composite lymphoma of PMBCL and classical Hodgkin lymphoma successfully treated with dose-adjusted EPOCH-R regimen.