Clear cell renal cell carcinoma with BAP1 mutation: a report of two cases.

Clear cell renal cell carcinoma is the most common subtype of renal cell carcinomas (RCCs) and accounts for 60%-70% of all RCCs cases in adults. Aberrations in the von Hippel-Lindau (VHL) gene on chromosome 3p occurred in > 90% of clear cell RCCs. Other tumor suppressor genes located on chromosome 3p, such as BAP1, PBRM1, and SETD2, also contribute to tumorigenesis. Clear cell RCCs with both BAP1 and VHL mutations may display distinctive histopathological features. Here, we report two cases of clear cell RCCs with BAP1 mutation. One tumor had VHL, BAP-1, and RAF1 mutations and the tumor nests and alveoli of tumor cells were surrounded by proliferative vessels and the optically clear cytoplasm contained numerous eosinophilic granules and hyaline globules of varying sizes. The other tumor had BAP1 and ATM mutations, and demonstrated clear cells with numerous eosinophilic granules and other typical histopathological features of conventional clear cell RCC. Furthermore, many tumor nodules with dense peripheral lymphocytic infiltrates contained rhabdoid cells. Sarcomatoid cells were also observed. Both tumor cells showed high-grade nuclei. Clear cell RCCs with BAP1 mutation exhibit aggressive clinical behaviors.

Renal cell carcinoma with leiomyomatous stroma: a review of an emerging entity distinct from clear cell conventional renal cell carcinoma.

Clear cell renal cell carcinomas accounts for 65 to 75% of all malignant renal tumors. The International Society of Urological Pathology 2012 Vancouver Classification of renal neoplasia and the World Health Organization 2016 Classification of renal tumors have included renal cell carcinoma with leiomyomatous stroma in a category of emerging/provisional entities of renal cell carcinoma. Macroscopically, renal cell carcinomas with leiomyomatous stroma are well circumscribed tumors with a cut surface of gray-white fibrotic tissues. Microscopically, the tumors are composed of nodules and anastomosing tubules of renal cells with clear cytoplasms. The carcinoma cells are embedded in a cellular stroma composed of intertwining bundles of smooth muscle. Immunohistochemically, the neoplastic cells are typically positive for CK7 and CD10 immunomarkers. Biomarkers including CAIX, pankeratin, vimentin, and HIF1-alpha stain positively in many renal cell carcinomas with leiomymomatous stroma. Molecular genetic studies of this variant of tumor reveal no VHL mutation, trisomy 7 or trisomy 17. However, a TCEB1 mutation has been demonstrated in a subset of tumors and rare cases are reported from patients with a family history of tuberous sclerosis. The biological behavior of this variant of tumor is indolent and the prognosis is favorable.

Prostatic adenocarcinoma with novel NTRK3 gene fusion: a case report.

TMPRSS2-ERG gene fusion occurs in approximately 50% of prostatic adenocarcinoma and their expression is associated with aggressive phenotype, higher tumor stage, and tumor metastasis. A case of prostatic adenocarcinoma with IRF2BP2-NTRK1 translocation was previously reported. We report a prostatic adenocarcinoma with novel NTRK3 gene fusion that occurs in a 71-year-old male patient with aggressive histologic phenotype and multiple bony metastases. Prostatic biopsy revealed that there is a prostatic adenocarcinoma with a Gleason score of 9 (4+5), grade group 5, and multiple sites of perineural and ganglional invasion. Fluorescence in-situ hybridization (FISH) and next-generation sequencing were performed. FISH studies showed a breakage within the NTRK3 gene in prostatic adenocarcinoma cells. Next-generation sequencing confirmed that there is a PRPSAP1-NTRK3 translocation in the prostatic adenocarcinoma. In addition, ASXL1, KIF5B, MED12, PIK3CA mutations were found. NTRK alterations or dysregulation of PI3K signaling pathway were found in many types of cancers. TRK inhibitors including larotrectinib and entrectinib were approved by the US Food and Drug Administration for treating TRK fusion-positive malignant tumors and PI3K/AKT/mTOR pathway inhibitors were under clinical studies on various cancers including prostate cancer. In our current case, both NTRK3 and PIK3CA may serve as biomarkers for precision targeted therapy.

The Use of a Novel Immunohistochemical Triple Cocktail in the Subclassification of Resected Non-Small Cell Lung Carcinomas: A Comparative Study With Morphology and Traditional Immunohistochemistry.

Therapy for non-small cell lung carcinoma (NSCLC) is currently determined by histologic subtype and the presence or absence of actionable mutations. Accurate subclassification is therefore essential for appropriate selection of cases for molecular studies and guiding treatment. The gold standard for subclassification of NSCLC is identification of differentiating morphologic features in correlation with diagnostic immunohistochemistry (IHC) in cases of poorly differentiated carcinoma. Whereas Napsin A, TTF1, and p40 antibodies have been used individually for the subtyping of NSCLC, few studies have examined the 3 in cocktail form. Using a novel triple IHC antibody cocktail (TNP) composed of TTF1 (brown nuclear), Napsin A (red granular cytoplasmic), and p40 (red nuclear), a randomized, double-blinded subclassification was performed on a representative histologic section of 32 previously resected primary NSCLCs. TNP results were then compared with the gold-standard diagnosis. TNP accurately identified all (100%, 10/10) squamous cell carcinomas (SCCs) (p40+/TTF1-/Napsin A-) and 89% (16/18) of adenocarcinomas (ADCs) (p40-/TTF1+/Napsin A+). TNP was negative in 7 (20%) tumors (p40-/TTF1-/Napsin A-), including 2 mucinous ADCs. TNP showed no overlapping or discordant immunostaining. Using traditional IHC with p63, CK5/6, and TTF1, all TNP (-) cases remained unclassifiable. With the exception of mucinous ADC, which was TNP negative, all TNP cases correlated with gold-standard diagnosis; 78% of tumors were also definitively classified as either ADC or SCC and required only a single slide for classification.

The Non-Innoculous Hilar Calcification: Recurrent Pneumonia Secondary to Broncholith-Associated Actinomyces.

Dystrophic calcification of hilar lymph nodes is a common response to chronic inflammation related to several etiologies and rarely is associated with any clinical findings. A clinical scenario related to these calcified lymph nodes can thus be delayed by the low clinical suspicion associated with such a presumably innocuous finding. Normal respiratory movements however, can cause erosion into adjacent bronchi leading to a broncholith, complications of which can result in morbidity. We illustrate one of these complications, a partial obstruction with subsequent recurrent infection due to normal oral flora - actinomyces.

ATYPICAL HEMOLYTIC UREMIC SYNDROME IN AN ADULT SUCCESSFULLY TREATED WITH ECULIZUMAB.

Atypical Hemolytic Uremic Syndrome is a triad of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure not associated with diarrhea. It is a rare condition associated with complement disorders in about 50 percent of cases. The first line of treatment is therapeutic plasma exchange. However, because clinical response to TPE varies, an anti-complement drug, eculizumab has been tried. We report a case of atypical HUS successfully treated with eculizumab.

Comparison of in vivo probe-based confocal laser endomicroscopy with histopathology in lung cancer: A move toward optical biopsy.

BACKGROUND AND OBJECTIVE: The development of novel technologies has increased the yield from transbronchial biopsies while preserving patient safety by guiding biopsies to the area of interest. Other technologies have helped identify pre-cancerous or sessile lesions in the endobronchial space by utilizing interactions between tissue and light at varying wavelengths. Probe-based confocal laser endomicroscopy (pCLE) is a new technology that encompasses the benefits of both guided biopsies and novel optical imaging in one device. This project compares pCLE images to the findings of light microscopy in non-small cell lung cancer (NSCLC). METHODS: Patients who underwent bronchoscopies between July 2012 and January 2013 for evaluation of pulmonary lesions (transbronchial and endobronchial) were recruited. Histopathological images from malignant lesions were compared with the pCLE images obtained from the same area. The microscopic and pCLE images were reviewed side by side with the microscopic findings. RESULTS: Images from pCLE correlate with some histopathological findings. pCLE changes seen in NSCLC consist of mottled elastin, septal studding and disorganization/fragmentation with increased friability. These changes also seem to correlate with degrees of differentiation. CONCLUSIONS: pCLE can identify changes to the elastin composition of the airways and alveoli in lung cancer. These changes correlate with histopathology and may help indicate the presence of malignant changes in vivo.