Erika E. Doxtader

Biopsy-site changes in lung adenocarcinoma with prior core needle biopsy: a potential pitfall in the assessment of stromal invasion.

Although biopsy-site changes are known to cause diagnostic difficulties in thyroid and breast specimens, especially when assessing invasion, such changes have not been described in the lung. Assessment of invasion is important in lung cancers to distinguish bronchioloalveolar carcinoma [adenocarcinoma in situ (AIS)] from invasive adenocarcinoma. The aim of this study was to determine whether biopsy-site changes occur in the lung and whether they may impact this differential diagnosis. Lobectomy specimens were examined from patients whose previous core needle biopsies showed well-differentiated adenocarcinoma with a lepidic pattern. There were 26 adenocarcinomas, including 14 minimally invasive adenocarcinomas, 2 invasive well-differentiated adenocarcinomas, and 10 AISs. Biopsy-site changes were identified in 9 of 26 (35%), including 4 minimally invasive adenocarcinomas, 3 AISs, and 2 well-differentiated adenocarcinomas. The interval between biopsy and resection ranged from 12 to 45 days (mean, 26.1 d). The biopsy sites consisted of a linear scar composed of collagen and plump fibroblasts, ranging from 2.0 to 13.1 mm in length and 0.5 to 1.6 mm in width. Scattered lymphocytes and plasma cells were present in 8 cases, pigment-laden macrophages in 4, and foreign body giant cells in 3. Benign entrapped lung epithelium was present within the scar in all 9 and entrapped malignant epithelium in 4. Biopsy-site changes can be identified in a significant proportion of lung tumors after core needle biopsy. They need to be distinguished from tumor-related stromal reactions that are considered an indication of invasion and are important in the differentiation of AIS and invasive adenocarcinoma.

Insulinoma-associated protein 1 is a sensitive and specific marker of neuroendocrine lung neoplasms in cytology specimens: INSM1 in Lung Cytology Specimens

Recent studies suggest that insulinoma‐associated protein 1 (INSM1) is a sensitive and specific marker of neuroendocrine neoplasms. The aims of this study were to determine whether INSM1 can be reliably used in cytology (Cellient) cell blocks, to ascertain whether staining correlates with paired surgical pathology specimens, and to compare its sensitivity and specificity with those of synaptophysin (SYN), chromogranin (CHR), and CD56 for neuroendocrine lung tumors.

Diagnosis of trichomoniasis in men by urine cytology

Trichomonas vaginalis is a rare finding in urine cytology specimens, especially those from men; only 2 case reports have been described in the literature. The authors of the current report sought to determine the incidence and clinical significance of this finding in urine cytology in males.

Molecular Testing of Non–Small Cell Lung Carcinoma Diagnosed by Endobronchial Ultrasound–Guided Transbronchial Fine-Needle Aspiration

CONTEXT.— Given the increasing demand for molecular testing of non-small cell lung carcinoma specimens to guide therapeutic decision-making and the trend toward minimally invasive techniques for obtaining diagnostic tissue, cytopathology laboratories must devise strategies to maximize DNA yield for necessary molecular testing. OBJECTIVE.— To describe our experience at Cleveland Clinic with epidermal growth factor receptor (EGFR) mutation testing by next-generation sequencing and anaplastic lymphoma kinase (ALK) gene rearrangement testing by fluorescence in situ hybridization of non-small cell lung carcinomas diagnosed by cytology, with an emphasis on specimens obtained by endobronchial ultrasound-guided transbronchial fine-needle aspiration. DATA SOURCES.— Data sources include a review of the current literature, including published articles from our institution. CONCLUSIONS.— At our institution, liquid-based cytology specimens are the primary resource used for molecular testing of non-small cell lung carcinomas; in most instances, adequate DNA can be extracted from the residual cell pellet for next-generation sequencing, and ThinPrep slides can be used reliably for fluorescence in situ hybridization testing for ALK gene rearrangements. In occasional cases where the cell pellet material is not adequate for molecular testing, cell blocks and/or surgical pathology specimens are secondary options. The cytopathologists role in specimen handling and triage is essential to ensure that molecular testing can be carried out successfully.

Solitary lung metastasis from intracranial hemangiopericytoma 18 years after initial resection

We report a 29-year-old woman who presented with severe headache, nausea and vomiting. A lesion was found in the left petrous ridge and near-total resection was performed. Pathologic examination showed anaplastic hemangiopericytoma (World Health Organization Grade III). Hemangiopericytoma is an uncommon mesenchymal tumor that rarely occurs in an intracranial location. Prior studies have reported a surprisingly high rate of late recurrence and extracranial metastases from intracranial hemangiopericytomas, including metastases to the lungs. Resection was followed by external beam radiation. The tumor recurred intracranially 6 and 13 years later and was treated with gamma knife stereotactic radiosurgery. At year 14, she noticed a lump in her neck and underwent parotidectomy for a mucoepidermoid carcinoma. This new diagnosis prompted a staging chest CT scan which showed a 4mm right upper lobe lung nodule along with additional < 5 mm indeterminate nodules. Over the next 3 years, the nodule increased to 8mm. Wedge biopsy of the lung nodule showed metastatic hemangiopericytoma, histologically similar to the intracranial hemangiopericytoma. Both the primary and the lung metastasis were positive for CD34 and STAT-6. To the best of our knowledge, this is the longest reported interval between a resected intracranial hemangiopericytoma and a histologically confirmed solitary metastasis to the lung.

Evaluation of Carcinoma of Unknown Primary on Cytologic Specimens

Carcinoma of unknown primary is defined as metastatic carcinoma without a clinically obvious primary tumor. Determining the tissue of origin in carcinoma of unknown primary is important for site-directed therapy. Immunohistochemistry is the most widely used tool for the work-up of metastases, but molecular profiling assays are also available. This review provides an overview of immunohistochemical stains in the work-up of metastatic carcinoma, with a focus on newer site-specific markers, and discusses the role of gene expression profiling assays for determining tissue of origin. The utility of cytopathology specimens in the evaluation of carcinoma of unknown primary also is highlighted.

Cytologic findings of an adult rhabdomyoma in the parapharyngeal space: A report of a case and review of the literature

Adult extracardiac rhabdomyomas are rare benign mesenchymal tumor arising from skeletal muscle. While they are often located in the larynx and pharynx, the incidence in the parapharyngeal area is extremely rare with only 1 documented cytology case report to date. We report a case of an adult extracardiac rhabdomyoma in the parapharyngeal space diagnosed cytologically with subsequent histologic confirmation. The patient is a 57‐year‐old man with history of weight loss, hematuria, dysphagia, and airway encroachment. Computerized tomography of his abdomen showed a large left renal mass. While the patient was in the operating room for the resection of his renal mass, a fine‐needle aspiration from left the parapharyngeal mass was performed. The smears showed uniform bland polygonal cells with abundant eosinophilic cytoplasm and peripherally located nuclei. Immunohistochemical stains performed on the cell block showed the tumor cells were desmin positive and negative for S‐100 and PAX‐8, supporting the diagnosis of an adult rhabdomyoma. Subsequent resection of the mass confirmed the diagnosis of an adult extracardiac rhabdomyoma.

Cystic pancreatic schwannoma diagnosed by endoscopic ultrasound-guided fine needle aspiration: DOXTADER et al.

A 78-year-old woman with chronic lymphocytic leukemia underwent imaging studies for evaluation of progressive disease. A cystic pancreatic mass was incidentally detected on abdominal computed tomogram (CT) scan. The lesion was further evaluated by magnetic resonance imaging (MRI), which showed a unilocular cyst in the posterior body of the pancreas measuring 1.4 × 1.3 cm. Endoscopic ultrasound examination was performed and demonstrated a 1.7 cm pancreatic cyst in the posterior portion of the pancreatic body, with a solid component and suspected nodular internal enhancement (Figure 1). The cystic portion was unilocular and without septae. The lesion did not appear to communicate with the main pancreatic duct. Two passes were made with a 22-gauge needle using a transgastric approach; 0.1 mL of opaque, white fluid was collected in CytoLyt® solution and submitted to the cytopathology laboratory, where a ThinPrep slide and CellientTM cell block were prepared. The ThinPrep showed cohesive tissue particles of varying cellular density with some degree of crowding and nuclear overlap. These particles contained sheets of bland spindle cells with variably rounded to tapered nuclear ends (Figure 2). The cytoplasm of these cells was fibrillar and syncytial-appearing, making delineation of exact cell sizes/ cell borders challenging. No mitotic activity or necrosis was present. Similar-appearing cellular fragments were present on cell block sections; the fragments contained relatively uniform spindled nuclei within an eosinophilic fibrillar-appearing background. The neoplastic cells were diffusely positive for S-100 (Figure 3), and were negative for CD117, DOG1, desmin, and AE1/AE3, confirming a diagnosis of schwannoma. Because of the benign nature of the lesion, surveillance with imaging studies was undertaken in lieu of resection. Follow-up imaging 11 months after initial diagnosis revealed an increase in size of the lesion by 1 cm. A repeat fine needle aspiration (FNA) yielded a similar appearing spindle cell neoplasm, consistent with schwannoma. Schwannomas are benign nerve sheath tumors commonly arising in the head and neck and extremities, and occasionally occurring in deep-seated locations including the posterior mediastinum and retroperitoneum. Their origin in the pancreas is rare, with fewer than 70 cases reported in the literature. In a recent review, Ma and colleagues summarized the features of 68 published cases of pancreatic schwannoma. Half of patients presented with abdominal pain, but 34% were asymptomatic. The lesions were most commonly located in either the head or the body of the pancreas, and the majority (65%) had a cystic component. Similar findings were reported by Moriya et al.in an earlier study. It is well known that schwannomas often show cystic degeneration, and this common feature of pancreatic schwannoma can mimic other cystic pancreatic lesions such as pseudocysts, serous or mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, solid pseudopapillary neoplasms or pancreatic neuroendocrine tumors with cystic change. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is increasingly performed for preoperative evaluation of pancreatic lesions, including pancreatic cysts. However, there are very few case reports in the cytology literature of pancreatic schwannoma diagnosed by FNA. In the cohort of cases reviewed by Ma

Cytopathologic features of papillary glioneuronal tumor

A 20-year-old woman with a history of systemic lupus erythematosus was admitted to the hospital with headaches, which began 6 weeks prior to admission. She was found to have a 1.6 cm enhancing left frontal lobe lesion by magnetic resonance imaging (Figure 1). During tumor resection tissue was sent for intraoperative consultation. Squash preparations and touch preparations were performed in addition to frozen sections. The smears and touch preparations were air-dried and stained with the Diff-Quik (modified Romanowsky) stain. Squash preparations showed numerous blood vessels. Many of the vessels contained loosely-attached cells with uniform, bland nuclei and scant cytoplasm. These cells were best seen in touch preparations, in which they had a discohesive pattern. Occasional intermixed cells had more abundant cytoplasm and eccentric nuclei (Figure 2). Formalin-fixed paraffin-embedded tissue sections revealed a striking pseudopapillary pattern at low magnification. The pseudopapillae contained hyalinized blood vessels, which were lined by a single layer of bland cuboidal cells with scant cytoplasm, which were immunopositive for glial fibrillary acidic protein (GFAP). In the intervening areas between pseudopapillae, occasional cells had eccentric nuclei and a moderate amount of cytoplasm; these cells were immunopositive for synaptophysin (Figure 3). There was no mitotic activity, necrosis, or vascular proliferation. Based on the morphologic and immunohistochemical findings, a diagnosis of papillary glioneuronal tumor was rendered. Papillary glioneuronal tumor is a rare intracranial tumor with both glial and neuronal components, occurring in the cerebral hemispheres predominantly in young patients. It was first described by Komori et al. in 1998, and was recognized as a distinct entity in the fourth edition of the WHO in 2007. Patients most commonly present with headaches or seizures. The tumor is often cystic, and may appear as a cyst with a mural nodule in imaging studies. Most cases have an excellent prognosis, and histologically correspond to WHO grade 1. The low-power morphologic appearance is distinctive, and fairly unusual for primary CNS tumors; the conspicuous pseudopapillae, composed of hyalinized blood vessels lined by one or several layers of bland cuboidal cells are seen in cytologic preparations as prominent blood vessels accompanied by small cells with uniform, bland nuclei and scant cytoplasm. The proportion of glial and neuronal elements can vary from case to case. Usually, the neuronal component is situated between the pseudopapillae in nests or sheets. Occasionally gangliocytic differentiation is seen. While the glial component is intensely immunopositive for GFAP, the neuronal component is GFAP-immunonegative and can be highlighted with immunohistochemical markers of neuronal differentiation such as synaptophysin, neuron-specific enolase (NSE), or NeuN. Intraoperative squash preparations and touch preparations are commonly performed on neuropathology specimens that are sent to the laboratory for frozen section diagnosis. Cytopathologic examination can be especially useful for assessing cellular detail when frozen section artifacts render interpretation of frozen section slides difficult. Although the cytopathologic features of papillary glioneuronal tumor