Chondroblastic osteosarcoma: Cytomorphologic characteristics and differential diagnosis on FNA.

BACKGROUND: Chondroblastic osteosarcoma (COS) is a uniformly fatal bone malignancy if not diagnosed and treated appropriately in a timely manner. Fine-needle aspiration (FNA) of osseous lesions is routinely performed in major medical centers. Appropriate characterization of the tumor will significantly influence patient management and outcomes. METHODS: A retrospective review of the cytopathology archives of 2 large tertiary care centers for a 15-year period (2001-2015) revealed 17 cases of COS (9 primary, 6 recurrent, and 2 metastatic cases) in 16 patients. Clinical outcome and histopathologic follow-up were reviewed and correlated. RESULTS: There were 9 male and 7 female patients (male-to-female ratio of approximately 1:1), ranging in age from 12 to 70 years (mean age, 29.2 years). The classic locations for osteosarcoma were commonly involved, such as the long bones around the region of the knee in 4 cases and the proximal humerus in 1 case. However, other "nonclassic" sites also were noted to be commonly involved, including the distal tibia or fibula (4 cases), sacroiliac region (4 cases), mandible (3 cases), and skull (1 case). Cytomorphologic characteristics were high cellularity; predominantly discohesive, single cells; small tissue fragments; background osteoid and chondroid matrix; spindled cells and plasmacytoid cells with moderate to abundant basophilic vacuolated cytoplasm and occasional multiple cytoplasmic processes; round to oval nuclei with anisonucleosis; and small to prominent nucleoli. There were scattered binucleated and multinucleated osteoclast-like giant cells. Cases with high-grade morphology demonstrated marked pleomorphism and abundant mitoses. CONCLUSIONS: The differential diagnosis of COS includes chondroblastoma, chondrosarcoma, and chondroid chordoma. A definitive diagnosis can be made with clinical and radiological correlation. Cancer Cytopathol 2016;124:493-500. © 2016 American Cancer Society.

Cytomorphologic overlap of differentiated thyroid carcinoma and lung adenocarcinoma and diagnostic value of TTF-1 and TGB on cytologic material.

Thyroid carcinomas and lung adenocarcinoma share cytomorphological features yet have different prognoses. Thyroid Transcription Factor-1 (TTF-1) is an immunohistochemical (IHC) marker used to confirm pulmonary and thyroid carcinoma, while Thyroglobulin (TGB) is expressed by thyroid carcinoma. The cytopathology archive of The Johns Hopkins Hospital was searched for cases of lung adenocarcinoma versus thyroid carcinoma with TTF-1 and TGB IHC. Forty-four cases of lung adenocarcinoma (25) and thyroid carcinoma (19) were retrieved. One was metastatic lung adenocarcinoma to the thyroid and three were metastatic papillary thyroid carcinoma (PTC) to the lung. The initial interpretation of two cases from bony lesions was metastatic lung adenocarcinoma. In light of additional clinical information and TGB immunostain, the diagnoses of these two cases changed to metastatic thyroid carcinoma. TTF-1 and TGB is a small immunostain panel that can differentiate lung adenocarcinoma from thyroid carcinoma and prevent misdiagnosis and its consequences.

Comparison of moderate versus deep sedation for endobronchial ultrasound transbronchial needle aspiration.

RATIONALE: Most bronchoscopic procedures are performed using moderate sedation achieved by combining a short-acting benzodiazepine with an opioid agent. Propofol (2.6-diisopropylphenol), a short-acting hypnotic agent, has been increasingly used to provide deep sedation in the endoscopy community with an acceptable safety profile. OBJECTIVES: To compare the impact of moderate versus deep sedation on the adequacy and diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). METHODS: A retrospective review of prospectively collected data was performed at two academic institutions with interventional pulmonary fellowships using two methods of sedation during EBUS (deep vs. moderate sedation). Rapid on-site cytologic evaluation was used on all procedures in both groups. EBUS-TBNA nodal sampling was considered adequate if the aspirate yielded a specific diagnosis or lymphocytes. EBUS-TBNA was considered diagnostic if a lymph node aspirate yielded a specific diagnosis or if subsequent surgical sampling or prolonged radiographic surveillance revealed no nodal pathology. MEASUREMENTS AND MAIN RESULTS: No difference was observed in the indication for EBUS-TBNA between the two groups. More lymph nodes were sampled per patient in the deep sedation group (314 nodes from 163 patients; 2.2 nodes per patient) than in the moderate sedation group (181 lymph nodes from 146 patients; 1.4 nodes per patient; P < 0.01). The EBUS-TBNA diagnostic yield was higher for the deep sedation group (80% of patients) than for the moderate sedation group (66% of patients; P < 0.01). CONCLUSIONS: Diagnostic yield and number of lymph nodes sampled using deep sedation is superior to moderate sedation in patients undergoing EBUS-TBNA. Prospective studies accounting for other factors including patient selection and cost are needed.

Urinary cytology of prostatic duct adenocarcinoma - a clinicopathologic analysis.

OBJECTIVE: To review atypical/positive urine cytology specimens from patients with confirmed prostatic duct adenocarcinoma (PDA), describe the cytomorphologic features and discuss the differential diagnosis. STUDY DESIGN: A retrospective review of the cytopathology archives of The Johns Hopkins Hospital revealed 14 cases of abnormal urinary cytology in patients with histologically confirmed PDAs. Cytologic material was reviewed; cytomorphologic characteristics were analyzed and correlated with histopathologic features wherever possible. RESULTS: There were 7 patients ranging in age from 52 to 80 years (mean age: 68 years). The clinical presentation included; hematuria, bladder obstruction and perineal mass. The cytomorphologic characteristics were: large crowded sheets and three-dimensional fragments (some with papillary architecture) of columnar epithelium with scant amphophilic cytoplasm, basally placed round to oval nuclei with coarse chromatin and absent or inconspicuous nucleoli. Histologic findings showed papillary and cribriform architecture of columnar cells with crowding, nuclear stratification and overlapping with or without nucleoli. CONCLUSION: PDAs usually present at an advanced clinical stage and may exfoliate owing to their location in the central prostatic urethra. Differentiating PDA from acinar prostatic adenocarcinoma, urothelial carcinoma and metastatic adenocarcinoma is important due to the differences in patient management. Since prostate-specific antigen values are variable, urine cytology may provide a valuable tool for the early detection of these aggressive lesions.

Malignant melanoma in neo-bladder urinary cytology: a brief report.

Malignant melanoma has an unusual predilection for metastasis to the small bowel, sometimes several years after the original diagnosis. In patients who have had a cystoprostatectomy followed by an ileal conduit, metastatic melanoma to the ileal conduit can present in urine cytology. We present a rare case of metastatic malignant melanoma in neo-bladder urine in a patient who had undergone a cystoprostatectomy for high grade urothelial carcinoma of the bladder and prostatic adenocarcinoma of Gleason grade 3+3 and two excisional procedures for cutaneous malignant melanoma. He presented with persistent hematuria and urinary tract infections unresponsive to treatment. Urine cytology revealed single large atypical cells, with large nuclei, prominent nucleoli, and cytoplasmic melanin pigment. Subsequent surgical resection revealed two areas of metastatic melanoma in the ileum, one of them being in the ileal conduit. The tumor cells were immunoreactive for S-100 protein, Melan-A, and HMB-45 and were negative for CAM5.2 and cytokeratins 7 and 20.

The Johns Hopkins Hospital template for urologic cytology samples: parts II and III: improving the predictability of indeterminate results in urinary cytologic samples: an outcomes and cytomorphologic study.

BACKGROUND: Urine cytology represents a major portion of testing volume in many cytopathology laboratories. METHODS: The authors previously reported a template designed to standardize urothelial diagnostic categories to enable clinicians to uniformly manage their patients. In this study, they examined the common cytomorphologic features observed in specimens diagnosed with atypical urothelial cells, cannot exclude high-grade urothelial carcinoma (AUC-H), which prove most predictive of high-grade urothelial carcinoma (HGUC). RESULTS: The most common morphologic features observed in the AUC-H specimens were hyperchromasia, irregular nuclear borders, increased nucleus-to-cytoplasm ratio, and anisonucleosis. Of the 58 patients who had specimens diagnosed with AUC-H, 95% ultimately were diagnosed with HGUC on follow-up biopsy over the study period. The small number of patients who had AUC-H with non-HGUC follow-up did not allow for a statistical comparison to determine the predictive ability of the selected criteria for HGUC. Next, the authors used the same features to examine a subset of urine samples that were diagnosed with atypical urothelial cells of unknown significance (AUC-US) in an attempt to improve the predictive value of this clinically frustrating category. A blind review was performed of 290 urine specimens from 217 patients. In contrast to the AUC-H specimen cohort, the majority of specimens with AUC-US did not contain atypical cells with the 4 common morphologic features. All 4 features significantly predicted HGUC in surveillance patients, but not in patients with hematuria. CONCLUSIONS: Hyperchromasia was the strongest predictor of HGUC by far in patients who were undergoing surveillance (odds ratio, 9.81). Hyperchromasia remained statistically significant in multivariate analysis, indicating its predictive strength even in the absence of other features.

The Johns Hopkins Hospital template for urologic cytology samples: part I-creating the template.

BACKGROUND: The most important indicator for urologic surgeons at The Johns Hopkins Hospital to have a patient undergo cystoscopy is a cytologic diagnosis of high-grade urothelial carcinoma. The template was designed to standardize diagnostic categories so clinicians can manage their patients uniformly. The template was based in part on the Bethesda System for cervical cytology. METHODS: According to the template, reactive/inflammatory changes were included in the negative group (no urothelial atypia or malignancy identified). The category atypical urothelial cells of undetermined significance (AUC-US) was akin to atypical squamous cells of undetermined significance (ASC-US), as was the category of atypical urothelial cells, favor high-grade carcinoma (AUC-H). The categories high-grade urothelial carcinoma (HGUC) and low-grade urothelial carcinoma also were added. RESULTS: The Pathology Data System at the Johns Hopkins Hospital was searched for cases that met the following criteria over a period from July 1, 2007 to June 30, 2009: all cytologic specimens from the urinary tract and all surgical specimens with a diagnosis of HGUC, regardless of invasion status. All cytologic specimens were then matched with biopsies during the same period, and all surgical specimens from patients who had a cytologic diagnosis of AUC-US or AUC-H were retrieved for 18 months after the end of the 2-year study period. Greater than 50% of patients who had biopsy-confirmed HGUC had a preceding cytologic diagnosis of AUC-H or HGUC. When patients with AUC-US were added to the analysis, 80% of patients with HGUC had at least 1 abnormal urinary cytology result. Of those patients who had a diagnosis of AUC-H, 38% had urothelial cancer discovered at biopsy compared with only 10% of those with an AUC-US diagnosis. CONCLUSIONS: The authors concluded that their template is effective in targeting those patients who need to undergo cystoscopy.

Osteoblastic osteosarcoma: cytomorphologic characteristics and differential diagnosis on fine-needle aspiration.

OBJECTIVES: To review cytomorphologic characteristics of osteoblastic osteosarcoma (OOS), a variant of osteosarcoma, on fine-needle aspiration (FNA) and correlate them with histopathologic features and clinical outcomes. STUDY DESIGN: A retrospective review of the cytopathology archives of The Johns Hopkins Hospital revealed 22 cases of OOS on FNA in 20 patients (16 primary, 5 recurrent and 1 metastatic OOS). RESULTS: There were 11 males and 9 females (male:female ratio 4:3) aged from 5 to 48 years (mean 17.1). Anatomic locations were: femur (7), humerus (3), tibia (4), fibula (1), iliac crest (1), pubis (1), sacrum (1), mandible (1) and soft tissue of the thigh (3). All except 1 presented with progressive pain and/or swelling. Sizes of the lesions ranged from 2.3 to 34 cm (mean 9.2). Initial FNA diagnoses were high-grade malignant neoplasm (5), osteosarcoma, non-conventional osteosarcoma (12) and OOS (5). Cytomorphologic characteristics were: moderate-high cellularity, discohesive/single cells, small tissue fragments, immature osteoid, bi-/multinucleated giant cells, plasmacytoid cells with basophilic, vacuolated cytoplasm, round to oval nuclei and macronucleoli. Cases with high-grade histology displayed pleomorphism and mitoses. CONCLUSIONS: OOS has a better prognosis than other osteosarcoma variants. The differential diagnosis of OOS includes reactive bone lesions, osteoblastoma, malignant sarcoma with an osteoid component and other osteosarcoma variants. A definitive diagnosis can be made on FNA with clinical and radiological correlation, thus facilitating immediate therapy.

Acute promyelocytic leukemia following chemotherapy for EBV-associated hemophagocytic lymphohistiocytosis.

We report a case of chemotherapy-related acute promyelocytic leukemia (APL) following therapy with VP-16/etoposide for EBV-associated hemophagocytic lymphohistiocytosis (HLH). A 17-month-old male presented with fever and lymphadenopathy. Bone marrow and liver biopsies showed hemophagocytosis. He responded well to chemotherapy including dexamethasone, VP-16/etoposide, and cyclosporine. One and a half year later, he developed fever and pancytopenia. Clinical work-up revealed APL with t(15;17)(q22;q12);PML-RARα translocation. He underwent chemotherapy for APL and is in remission 8 years after diagnosis. Alternative non-leukemogenic agents to effectively treat HLH would be desirable.