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FNAB cytology of extra-cranial metastasis of glioblastoma multiforme may resemble a lung primary: a diagnostic pitfall.

BACKGROUND: As extra-cranial metastasis of glioblastoma multiforme (GBM) is rare, it may create a diagnostic dilemma especially during interpretation of fine needle aspiration biopsy (FNAB) cytology. CASE PRESENTATION: We present transbronchial FNAB findings in a 62-year-old smoker with lung mass clinically suspicious for a lung primary. The smears of transbronchial FNAB showed groups of cells with ill-defined cell margins and cytological features overlapping with poorly differentiated non-small cell carcinoma. The tumor cells demonstrated lack of immunoreactivity for cytokeratin, thyroid transcription factor-1, and usual neuroendocrine markers, synaptophysin and chromogranin in formalin-fixed cellblock sections. However, they were immunoreactive for the other neuroendocrine immunomarker, CD56, suggesting neural nature of the cells. Further scrutiny of clinical details revealed a history of GBM, 13 months status-post surgical excision with radiation therapy and systemic chemotherapy. The tumor recurred 7 months earlier and was debulked surgically and with intra-cranial chemotherapy. Additional evaluation of tumor cells for glial fibrillary acidic protein (GFAP) immunoreactivity with clinical details resulted in final interpretation of metastatic GBM. CONCLUSION: Lack of clinical history and immunophenotyping may lead to a diagnostic pitfall with possible misinterpretation of metastatic GBM as poorly differentiated non-small cell carcinoma of lung in a smoker.

Journal Article↗

Splenic abscess: a diagnostic pitfall in the ED.

Splenic abscess, with its rare incidence and various misleading clinical manifestations, usually is a diagnostic pitfall in the modern emergency department. The most frequently seen symptoms and signs are fever, abdominal pain and tenderness over left upper quadrant, splenomegaly, leucocytosis, and left lower chest abnormalities. Four cases were collected during the past five years. On admission, one patient manifested symptoms mimicking a perforated peptic ulcer and the other three patients presented clinical and roentgenographic signs suggestive, but non-specific, for splenic abscess. In two cases, the diagnosis was based on sonography followed by computed tomography (CT). In one case, the splenic abscess was only visualized by CT. They all survived after splenectomy and appropriate antibiotic therapy. Culturing disclosed the offending organisms to be Escherichia coli, Pseudomonas aeruginosa, a Salmonella species, and Streptococcus viridans. These nonspecific clinical pictures should be thoroughly investigated, and CT, the most sensitive diagnostic tool, should be used whenever splenic abscess is suspected. Early diagnosis and timely treatment reduce the morbidity and mortality associated with splenic abscess.

Abdominal Pain↗

Diagnostic pitfalls in patients with hypoxic brain damage: three case reports.

OBJECTIVE: Our aim was to assess the possible diagnostic pitfalls in three patients with hypoxic brain damage who had partly conflicting clinical, biochemical, and electrophysiological data and were in a persistent vegetative state (PVS) following cardiac arrest (CA). METHODS: Serum concentrations of the destruction proteins, neuron-specific enolase (NSE) and protein S-100B (S-100B), were measured on days 1-3, and 7; somatosensory evoked potentials (SEPs) were recorded within 48 h and on day 7 after CA. RESULTS: Two patients had significantly increased concentrations of NSE and S-100B during the first 3 days after CA, a finding that indicates ongoing neuronal destruction. In contrast, the SEPs of these patients were normal or showed only a diminished amplitude configuration. In the third patient the SEPs demonstrated a bilateral loss of cortical responses repeatedly, but both destruction proteins were only slightly above the upper normal values on all study days. CONCLUSION: Our findings demonstrate that a poor prognosis can only be established if either SEPs, NSE, or S-100B are very abnormal. The conflicting results in our patients indicate that variable values may reflect different patterns of neuropathological damage caused by diffuse hypoxia. We, therefore, favour a multi-modal approach with a combination of clinical, biochemical, and electrophysiological investigations in order to predict neurological outcome after CA reliably.

Cardiopulmonary Resuscitation↗

Amyloid in cytologic specimens. Differential diagnosis and diagnostic pitfalls.

OBJECTIVE: To describe and illustrate the characteristic features of amyloid in cytologic preparations and point out its diagnostic pitfalls. STUDY DESIGN: Five fine needle aspirates and one bronchial washing that contained amyloid were retrospectively reviewed. The aspirates were obtained from each of the five following sites: lung, occipital lymph node, thyroid gland, proximal humerus and subcutaneous soft tissue. Smears of all of the aspirates were stained with Papanicolaou stain, and in two cases they were also stained with Diff-Quik. Cell block sections were stained with hematoxylin and eosin. Congo red, CD45 and CD20 were used on selected cases. RESULTS: Amyloid appears as either flocculent material or irregularly shaped fragments with scalloped and pointed edges. The amorphous fragments are acellular and frequently associated with connective tissue cells. They stain eosinophilic to cyanophilic with Papanicolaou stain and deep blue with Diff-Quik. In two cases an exuberant giant cell reaction almost obscured the amyloid. In the thyroid aspirate, the amyloid was misinterpreted as colloid. In bronchial washings and lung aspirates, amyloid has to be distinguished from mucus, alveolar proteinosis, chondroid material and corpora amylacea. When circumferentially surrounded by lymphocytes or plasma cells, flocculent amyloid deposits may simulate adenoid cystic carcinoma. CONCLUSION: Amyloid can be easily overlooked or mistaken for other entities with similar staining qualities. Congo red staining can help to confirm the diagnosis.

Aged↗

Extraneous cells of hepatic origin in adrenal fine needle aspiration as a diagnostic pitfall: a case report.

BACKGROUND: The fine needle aspiration (FNA) cytologic evaluations of most adrenal lesions are straightforward. However, there are diagnostic pitfalls to be avoided. CASE: A 34-year-old, pregnant woman was discovered to have an asymptomatic, right upper abdominal mass on ultrasound examination. After delivery, computed tomography-guided FNA showed bland epithelial cells, and a diagnosis of adrenal cortical adenoma was made. However, subsequent resection showed a myelolipoma of the adrenal gland. CONCLUSION: This case illustrated 2 cytodiagnostic pitfalls in adrenal fine needle aspirates. First, the myeloid cells characteristic of a myelolipoma were not present in the FNA smears because a large portion of the lesion was composed of fibroadipose tissue. Second, extraneous, benign cells of hepatic origin were misinterpreted as adrenal cortical adenoma cells.

Adrenal Cortex Neoplasms↗

Diagnostic pitfalls of peritoneal washing cytology and the role of cell blocks in their diagnosis.

Mesothelial cell hyperplasia, collagen balls, endometriosis, and endosalpingiosis are diagnostic pitfalls on peritoneal washing cytology in women who present with gynecologic lesions. Over an 8-month period, the peritoneal washings from 10 patients undergoing gynecologic surgery for presumed malignancy showed unusual cytologic findings, several of which posed diagnostic difficulties. The washings from four patients with ovarian carcinomas were cellular and contained clusters and strips of cells with cytologic atypia mimicking malignancy. Confirmation of their benign mesothelial origin was confirmed on immunohistochemistry utilizing cell block preparations. In two cases of endometrial endometrioid carcinoma, the washings contained several clusters of cells surrounding and/or admixed with a globular substance. Due to their similarity to endometrial cells, immunohistochemistry was performed on cell block preparations. The cells were positive for cytokeratin and negative for carcinoembryonic antigen and B72.3, confirming their mesothelial origin. In one case, clinically presumed to be a malignant mass, the washings contained tight clusters of cells with mild cytologic atypia admixed with hemosiderin-laden macrophages. In conjunction with the cell block findings, a diagnosis of endometriosis was made. Extensive endometriosis was found on the surgically resected specimen. In two cases, strips of ciliated epithelial cells resembling tubal epithelium were present on the cytologic and cell block preparations, consistent with endosalpingiosis. The peritoneal washings in one case contained several clusters and balls of atypical cells surrounding microcalcifications on cell block preparation. Since calcification within groups of cells in peritoneal washings always raised the possibility of malignancy, a serous carcinoma of the ovary, particularly of borderline malignancy, would have to be excluded. Fortunately, the resected specimen was free of tumor and showed calcified endosalpingiosis on the ovarian surface. Preparation of cell blocks from peritoneal washings is of value in the work-up and management of patients who present with cytologic mimickers of malignancy on fluid cytology.

Adult↗

Helical CT for the evaluation of suspected acute pulmonary embolism: diagnostic pitfalls.

Helical CT is being increasingly utilized for the evaluation of suspected pulmonary embolism (PE). Proper scan interpretation depends on the awareness of several diagnostic pitfalls that may simulate PE, including normal bronchovascular structures such as pulmonary veins, bronchi, and lymph nodes, technical considerations such as improper bolus timing and streak artifacts, and patient-related factors such as motion artifacts, pulmonary arterial catheters, and vascular shunts. An understanding of these pitfalls facilitates accurate diagnosis.

Acute Disease↗

Diagnostic pitfalls in food allergy in children.

Currently, the diagnostic work-up of suspected food allergy includes skin prick tests, the measurement of food specific immunoglobulin E (IgE), and the atopy patch test, and double-blind, placebo-controlled food challenges. However, all of these methods, even double-blind, placebo-controlled food challenges (DBPCFC), may sometimes be misleading. This overview describes several pitfalls for standard diagnostic methods such as problems with irritative skin reactions mimicking IgE-mediated symptoms, the problem of non-IgE-mediated reactions, pitfalls arising from the way foods are prepared or processed, effects of the route of exposure, the role of augmentation factors lowering the threshold value for clinical reactions, the noncomparability of specific IgE decision points, the influence of the timing of diagnostic measures. In addition, the problem of alternative diagnostic measures is discussed. In conclusion, there are several pitfalls in the diagnostic work-up of food allergy, which may be misleading for the physician. Properly performed controlled oral food challenges still represent the gold standard for implementing specific diets in food allergic individuals in order to avoid both unjustified diets, which may lead to severe impairments in growth and development, and to avoid unnecessary symptoms if an underlying food allergy is not correctly identified as a cause for the symptoms of the patient.

Child↗

Multilocular renal cyst: a diagnostic pitfall on fine-needle aspiration cytology: case report.

Benign renal lesions, apart from simple cysts, are rarely sampled by fine-needle aspiration biopsy (FNAB) and are potential diagnostic pitfalls. A complex renal mass in a 33-yr-old pregnant woman, presenting in the second trimester with haematuria, was aspirated twice, a week apart, under ultrasound guidance. The second FNAB yielded predominantly mesenchymal elements thought to represent an angiomyolipoma, but the mass was identified as a multilocular renal cyst (MLRC) on the nephrectomy specimen. Differential diagnoses of angiomyolipoma, MLRC, and renal cell carcinoma (RCC) are compared and discussed in relation to patient management.

Adult↗

Endometrial atypical (bizarre) stromal cells: a potential diagnostic pitfall in biopsy.

Atypical stromal cells (ASCs) may be detected in endometrial polyps and, more rarely, in normal endometrium. Owing to their worrisome cytological features, these cells may represent a potential diagnostic pitfall and are often misinterpreted as malignant, particularly in biopsy samples. We report on ASCs in proliferative phase endometrium of a woman who underwent biopsy for vaginal bleeding. Morphological and immunohistochemical features are discussed in detail. The differential diagnosis to endometrial malignant tumors containing atypical mesenchymal cells is provided.

Biopsy↗

"Arias-Stella reaction"-like changes in endocervical glandular epithelium in cervical smears during pregnancy and postpartum states--a potential diagnostic pitfall.

A wide spectrum of histologic changes has been described throughout the female genital tract during pregnancy and in the postpartum period. Of these, the endometrial glandular changes referred to as the Arias-Stella reaction have classically been a diagnostic pitfall in histologic sections. Pregnancy-related changes are also reflected in cytologic material obtained from the cervix and vagina. Both glandular and stromal alterations may be seen. The changes involving endocervical glandular epithelium are often alarming enough to cause diagnostic difficulties, especially when the history of pregnancy is not provided. We report 13 cases where marked glandular changes led to diagnostic misinterpretations. These were characterized by cyto- and karyomegaly, a high nuclear to cytoplasmic ratio, round to oval nuclei with smudgy chromatin imparting a ground glass appearance, frequent intranuclear inclusions, and vacuolated to dense variable cytoplasm. The cytologic diagnoses ranged from "glandular atypia" to "suspicious for adenocarcinoma." Follow-up was available in 11/13 cases. In 9/11 cases, subsequent cervical smears on multiple occasions were negative. Cervical biopsies and/or dilatation and curettage in 4/11 cases did not show significant glandular abnormalities. The glandular changes encountered in cytologic material were similar to those described histologically in the Arias-Stella reaction involving the cervix. This similarity and the fact that these changes disappeared upon termination of the pregnancy favors the presumption that they represent the Arias-Stella reaction. Awareness of these changes during pregnancy and postpartum may prevent interpretive errors and unnecessary surgical procedures.

Adolescent↗

[Diagnostic pitfalls in infectious disease pathology].

Numerous images observed in histopathology and cytopathology can mimic pathogens such as mycotic agents, parasites (protozoa or helminthes), bacteria or virus. An error of diagnosis may provoke the administration of a non efficient treatment which can also be toxic. The present review describes these false pathogens which can correspond to exogenous or endogenous agents. Basic morphological analysis of mycotic agents, parasites, bacteria and cytopathogenic viral effects are successively presented. Then, the main diagnostic pitfalls which can be observed during these infections are exposed. Finally, diagnostic problems occurring in case of contamination are rapidly cited.

Bacterial Infections↗

Chylothorax as a possible diagnostic pitfall: a report of 2 cases with cytologic findings.

BACKGROUND: Chyothorax is an uncommon medical condition. To the best of our knowledge, there have been no detailed English-language report dealing with its cytopathologic findings and diagnostic pitfalls CASES: A 12-year-old boy, hemodialysis dependent, with congenital nephrotic syndrome due to focal segmental glomerular sclerosis and a failed renal transplant, developed shortness of breath. Physical and radiologic examinations revealed a left pleural effusion. A 7-year-old boy developed shortness of breath, with a subsequent finding of a left pleural effusion. Multiple osteolytic skeletal lesions were found in this patient. Both patients underwent thoracocentesis. Cytologically, both fluids contained many relatively uniform, large lymphoid cells with high nuclear/cytoplasmic (N/C) ratio, condensed chromatin and occasional nucleoli, resembling blasts. Some nuclei were convoluted. Mitotic figures were present. Foamy macrophages were present in both cases. The differential diagnosis of these populations of cells included a lymphoproliferative disorder. However, the mature T-lymphocytic nature of the cells was confirmed by immunohistochemistry performed on cell block preparations, confirming the clinical impression of chylothorax in both cases. The first patient had chylothorax as a result of trauma due to therapeutic interventions (subclavian vein cannulation), in the second patient the chylothorax was a part of Gorham-Stout syndrome. CONCLUSION: The large T-lymphocytes that are the major cellular component of chylothorax may arouse suspicion of a lymphoproliferative disorder. Attention to the clinical history and immunophenotyping confirm the benign nature of the pleural space fluid. Also, abundant foamy macrophages can be considered a low-power clue to this diagnosis.

Child↗

Fine needle aspiration biopsy of hepatic leiomyosarcoma. An unusual epithelioid variant posing a potential diagnostic pitfall in a hepatocellular carcinoma-prevalent population.

OBJECTIVE: To study the cytomorphologic features of hepatic smooth muscle tumors on fine needle aspiration biopsy (FNAB) material in a hepatocellular carcinoma (HCC)-prevalent population, in which a potential diagnostic pitfall is an unusual variant of metastatic epithelioid leiomyosarcoma seen on aspiration cytology. STUDY DESIGN: FNABs of five cases of metastatic hepatic leiomyosarcomas were studied cytohistologically and immunocytochemically. In addition, ultrastructural studies were performed in one unusual case. Resected hepatic specimens and all other relevant histopathologic specimens were reviewed. RESULTS: Classically, aspirates of leiomyosarcoma produced syncytial masses of spindle cells characterized by overlapping, cigar-shaped nuclei and truncated ends. An unusual variant of metastatic epitheliod leiomyosarcoma was studied, with cytohistologic, immunohistochemical and ultrastructural correlation. CONCLUSION: Hepatic spindle cell lesions consist mainly of metastatic leiomyosarcomas. The diagnosis of malignancy and metastatic status of hepatic smooth muscle tumors is facilitated by the presence of an extrahepatic primary tumor. In a hepatitis B virus-endemic population, HCC, sarcomatoid type, has to be considered in the differential diagnosis of hepatic spindle cell lesions and the classic type, in epithelioid variants of smooth muscle tumors.

Adult↗

Chronic lymphocytic leukemia/small lymphocytic lymphoma with trisomy 12 and focal cyclin d1 expression: a potential diagnostic pitfall.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma usually are distinctly different in regard to clinical presentation, morphology, immunophenotype, and molecular/genetic findings. In spite of this, select cases may show overlapping characteristics and represent a diagnostic challenge. Cyclin D1 immunohistochemical staining is usually envisioned as a definitive method for resolving this differential diagnosis, with positivity supporting a diagnosis of mantle cell lymphoma. We report a case involving a 58-year-old man with a diagnosis of CLL/SLL for several years. A lymph node excision was performed after increased adenopathy was noted in the cervical region. The excised lymph node showed typical morphologic findings of CLL/SLL, including the presence of characteristic proliferation centers. Cyclin D1 staining, using 3 different antibodies, was present in scattered prolymphocytes and paraimmunoblasts, mostly within proliferation centers. Fluorescence in situ hybridization and conventional cytogenetics demonstrated trisomy 12 and an absence of t(11;14) in lymph node tissue. Focal cyclin D1 expression by immunohistochemistry in nodal CLL/SLL is quite unusual and is discussed as a potential diagnostic pitfall.

Chromosomes, Human, Pair 12↗

CD56 staining in Merkel cell carcinoma and natural killer-cell lymphoma: magic bullet, diagnostic pitfall, or both?

BACKGROUND: Antibodies to CD56 label natural killer (NK) cell lymphomas and neuroendocrine tumors such as Merkel cell carcinoma (MCC). In MCC altered by crush artifact or obscured by lymphocytes, the histologic features coupled with CD56 positivity can lead to an erroneous impression of NK-cell lymphoma. METHODS: Eighteen cases of MCC were stained for CD56, CK20, MNF116, and pankeratin. The results were compared to histologic features and CD56 staining pattern of three NK-cell lymphomas. RESULTS: Three of 18 cases of MCC histologically resembled lymphoma, and CD56 positivity with CD3 and CD20 negativity initially raised the possibility of NK-cell lymphoma. Two additional cases were obscured by dense inflammation, again suggesting the diagnosis of lymphoma. Seventeen of 18 MCC labeled for CD56 and an equal number stained for CK20. All MCC tested were positive for CAM5.2 (14/14) and MNF116 (17/17). Antibodies to pankeratin labeled only one of 18 MCC. Staining for CD56 was stronger in MCC than NK-cell lymphomas. CONCLUSIONS: CD56 is a sensitive marker for MCC as well as for NK-cell lymphoma, but is not specific. Importantly, CD56 positivity in crushed or inflamed biopsies of MCC may lead to an erroneous impression of NK lymphoma. Awareness of this potential pitfall will prevent misdiagnosis. McNiff JM, Cowper SE, Lazova R, Subtil A, Glusac EJ. CD56 staining in Merkel cell carcinoma and natural killer-cell lymphoma: Magic bullet, diagnostic pitfall, or both?

Aged↗