Recurrent Primary Peritoneal Psammocarcinoma: A Case Report on a Diagnostic Challenge in Cytology.

Psammocarcinoma (PCa) is a rare variant of low-grade papillary serous carcinoma that can arise from the peritoneal as well as ovarian surfaces. When this tumor involves the extra-ovarian peritoneum significantly and the ovarian surface minimally or not at all, it is considered of peritoneal origin. PCa has a recurrent indolent clinical course. It is challenging to diagnose peritoneal PCa, particularly on cytological smears because of the bland cellular features of neoplastic cells. We report a case of recurrent metastatic primary peritoneal PCa in a 71-year-old female of Ashkenazi Jewish ancestry diagnosed on cytology of ascitic and cystic fluid.

When accurate cytomorphology directs clinical decision: Colonic adenocarcinoma presents initially with an isolated vertebral bone metastasis.

Liver is the most common site for metastasis of colonic adenocarcinoma. Other relatively common metastatic locations include: peritoneum, lungs and ovaries. Rare metastatic sites include: central nervous system, testis, uterus, oral cavity and bones. Though it is rare to have an isolated bone metastasis without liver or visceral involvement in colonic adenocarcinoma, it can occur. Our case illustrates the vital role of an accurate cytopathologic diagnosis in directing the proper clinical decision and management in our young patient. Our patient's first presentation was acute on chronic back pain radiating to his lower extremities with clinical suspicion of tuberculosis spondylitis. The correct cytopathologic diagnosis of the fine needle aspiration from the destructive vertebral lesion led to the establishment of an isolated metastatic colonic adenocarcinoma diagnosis initially and directed the clinical management of our patient.

Differentiating Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features from Classic Papillary Thyroid Carcinoma: Analysis of Cytomorphologic Descriptions Using a Novel Machine-Learning Approach.

BACKGROUND: Recent studies show various cytomorphologic features that can assist in the differentiation of classic papillary thyroid carcinoma (cPTC) from noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Differentiating these two entities changes the clinical management significantly. We evaluated the performance of support vector machine (SVM), a machine learning algorithm, in differentiating cases of NIFTP and encapsulated follicular variant of papillary thyroid carcinoma with no capsular or lymphovascular invasion (EFVPTC) from cases of cPTC with the use of microscopic descriptions. SVM is a supervised learning algorithm used in classification problems. It assigns the input data to one of two categories by building a model based on a set of training examples (learning) and then using that learned model to classify new examples. METHODS: Surgical pathology cases with the diagnosis of cPTC, NIFTP, and EFVPTC, were obtained from the laboratory information system. Only cases with existing fine-needle aspiration matching the tumor and available microscopic description were included. NIFTP cases with ipsilateral micro-PTC were excluded. The final cohort consisted of 59 cases (29 cPTCs and 30 NIFTP/EFVPTCs). RESULTS: SVM successfully differentiated cPTC from NIFTP/EFVPTC 76.05 ± 0.96% of times (above chance, P < 0.05) with the sensitivity of 72.6% and specificity of 81.6% in detecting cPTC. CONCLUSIONS: This machine learning algorithm was successful in distinguishing NIFTP/EFVPTC from cPTC. Our results are compatible with the prior studies, which show cytologic features are helpful in differentiating these two entities. Furthermore, this study shows the power and potential of this approach for clinical use and in developing data-driven scoring systems, which can guide cytopathology and surgical pathology diagnosis.

A worm in the cytology laboratory: A root cause analysis case study.

In the spring of 2018, nematode-like organisms were first noted at the time of microscopic diagnosis on gynecologic (GYN) and anal pap specimens in our institution's cytopathology department. Due to their morphology and specimen source, we considered a diagnosis of pinworm. However, after identifying at least 30 more cases over 3 months from patients living in variable locations, we started favoring a contaminant. This report studies the steps that were initiated to figure the source of pap smear-preparation contamination and the molecular investigation to identify the nature of the contaminant.

Frequency and pathological characteristics of drug-induced liver injury in a tertiary medical center.

Drug-induced liver injury (DILI) accounts for approximately 10% of acute hepatitis cases. DILI can arise as idiosyncratic or intrinsic injury from hundreds of drugs, herbals, and nutritional supplements and is essential to recognize as one of the differential diagnoses of hepatitis in a liver biopsy. The purpose of this study is to investigate the frequency and pathological characteristics of DILI related to the variety of hepatotoxic agents. We searched our pathology database for all patients with hepatitis diagnosed on liver biopsy from January 2012 to May 2016, and selected patients with a diagnosis of DILI. Electronic medical records were reviewed for patient medication list, history of herbal medicine or supplement use, and pre-biopsy liver function test (LFT) results. Clinical and pathologic correlation was used to determine the causative or related agents for DILI. We then assessed histopathologic features of liver injury and categorized biopsy findings as primarily bile duct injury, lobular/portal hepatitis, or mixed changes. Six hundred four total liver biopsies for hepatitis or liver injury were identified, of which 70 cases (11.6%) carried the diagnosis of DILI confirmed by clinical correlation. The most common etiologies associated with DILI were supplements and herbal products (31.4%), antimicrobials (14.3%), chemotherapeutics (11.4%), antilipidemics (7.1%) and immunomodulatory agents (7.1%). LFT results positively correlated with histological findings. Nutritional/herbal supplements have emerged as one of the major hepatotoxicity agents. DILI can manifest as predominantly hepatitis, bile duct injury or combination. Histological pattern recognition in the liver biopsy may help identify specific hepatotoxic agents causing DILI.

Clinical features, histology, and histogenesis of combined hepatocellular-cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (CHC) is a rare tumor with poor prognosis, with incidence ranging from 1.0%-4.7% of all primary hepatic tumors. This entity will be soon renamed as hepato-cholangiocarcinoma. The known risk factors for hepatocellular carcinoma (HCC) have been implicated for CHC including viral hepatitis and cirrhosis. It is difficult to diagnose this tumor pre-operatively. The predominant histologic component within the tumor largely determines the predominant radiographic features making it a difficult distinction. Heterogeneous and overlapping imaging features of HCC and cholangiocarcinoma should raise the suspicion for CHC and multiple core biopsies (from different areas of tumor) are recommended before administering treatment. Serum tumor markers CA19-9 and alpha-fetoprotein can aid in the diagnosis, but it remains a challenging diagnosis prior to resection. There is sufficient data to support bipotent hepatic progenitor cells as the cell of origin for CHC. The current World Health Organization classification categorizes two main types of CHC based on histo-morphological features: Classical type and CHC with stem cell features. Liver transplant is one of the available treatment modalities with other management options including transarterial chemoembolization, radiofrequency ablation, and percutaneous ethanol injection. We present a review paper on CHC highlighting the risk factors, origin, histological classification and therapeutic modalities.

The TGF-ß/Smad4 Signaling Pathway in Pancreatic Carcinogenesis and Its Clinical Significance.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human cancers due to its complicated genomic instability. PDAC frequently presents at an advanced stage with extensive metastasis, which portends a poor prognosis. The known risk factors associated with PDAC include advanced age, smoking, long-standing chronic pancreatitis, obesity, and diabetes. Its association with genomic and somatic mutations is the most important factor for its aggressiveness. The most common gene mutations associated with PDAC include KRas2, p16, TP53, and Smad4. Among these, Smad4 mutation is relatively specific and its inactivation is found in more than 50% of invasive pancreatic adenocarcinomas. Smad4 is a member of the Smad family of signal transducers and acts as a central mediator of transforming growth factor beta (TGF-ß) signaling pathways. The TGF-ß signaling pathway promotes many physiological processes, including cell growth, differentiation, proliferation, fibrosis, and scar formation. It also plays a major role in the development of tumors through induction of angiogenesis and immune suppression. In this review, we will discuss the molecular mechanism of TGF-ß/Smad4 signaling in the pathogenesis of pancreatic adenocarcinoma and its clinical implication, particularly potential as a prognostic factor and a therapeutic target.

Adrenal Cushing syndrome with detectable ACTH from an unexpected source.

Mixed corticomedullary adrenal tumours (MCMT) are rare. We describe the second reported case of a male patient presenting with hypertension and Cushing syndrome with MCMT. A man aged 48 years presented with hypertension and signs of Cushing syndrome. 24-hour urine cortisol was elevated, with detectable adrenocorticotropic hormone (ACTH). A high-dose dexamethasone suppression test indicated an adrenal or ectopic Cushing syndrome. Plasma metanephrines were normal. A 3 cm left adrenal mass was identified without potential ectopic sources of ACTH on imaging. After induction of anaesthesia for laparoscopic adrenalectomy, the patient developed resistant hypertension with stress-dose hydrocortisone administration. Surgery was cancelled and repeat testing revealed elevated plasma metanephrines. α-Blockade was administered for a presumed coexisting pheochromocytoma, and the patient underwent adrenalectomy. Pathology revealed an MCMT. This case highlights the importance of a thorough biochemical evaluation in patients with adrenal masses to rule out multiple hormone producing tumours.

Blastic plasmacytoid dendritic cell neoplasm: evolving insights in an aggressive hematopoietic malignancy with a predilection of skin involvement.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) derived from precursors of plasmacytoid dendritic cells is a very rare, unique, and highly aggressive immature hematopoietic malignancy, more frequently occurring among healthy elderly adults. BPDCN can be characterized by a striking predilection for cutaneous involvement, which is often detected incidentally by dermatologists and is difficult to clinically distinguish it from other primary skin lesions and histologically from leukemia/lymphoma cutis. Thus, histological diagnosis of cutaneous biopsies is crucial to correctly classify this entity. Most patients eventually progress to acute myeloid leukemia and are generally not curable. Here, we present 2 cases of classic BPDCN and discuss the origin of tumor and literature-based characteristic clinical and morphological features, evolving immunomarkers, and molecular genetic aspects of this neoplasm.