Diagnosis and subclassification of thymoma by minimally invasive fine needle aspiration directed by endobronchial ultrasound: a review and discussion of four cases

Thymomas have been classified by the World Health Organisation (WHO) into six groups, based on the morphology of epithelial cells and the ratio between epithelial cells and lymphocytes within the tumour. Among 1458 consecutive cases of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) performed in a tertiary referral centre between February 2008 and February 2012, we have encountered four cases of thymic neoplasms. We discuss the cytomorphological features of three cases of type B thymoma (one each of B1, B2 and B3 subtypes) and one case of thymic carcinoma diagnosed on EBUS-TBNA using cell blocks, immunocytochemistry and flow cytometry which allowed preoperative chemotherapy to be carried out in two cases, diagnosis to be made after unsatisfactory surgical mediastinoscopy in the third and diagnosis of lymph node metastasis of the thymic carcinoma in the fourth. The differential diagnosis and criteria for subclassification of thymomas are discussed; although subclassification of these cases was possible in these cases, and tumours other than thymoma excluded, additional cases would be necessary to assess the potential accuracy of EBUS-TBNA. These, to the best of our knowledge, represent the first cases of thymoma that were diagnosed and subclassified according to WHO criteria using multimodality evaluation of EBUS-derived cytological aspirates.     

Value of immunocytochemistry in aspiration cytology of sacrococcygeal chordoma. A report of two cases.

Two cases of saccrococcygeal chordoma that were diagnosed on the basis of smear preparations are presented. Only one case showed typical physaliferous cells. In both cases the final diagnosis was greatly facilitated by applying peroxidase-antiperoxidase immunocytochemistry techniques to the cytologic specimens. Chordomas coexpress epithelial markers, such as intermediate filaments of the cytokeratin type, epithelial antigens (such as tissue polypeptide and epithelial membrane antigen), intermediate filaments of the vimentin type and S-100 protein. This antigenic spectrum may greatly facilitate the differential diagnosis of chordoma from filum terminale ependymoma, chondroma and chondrosarcoma, metastases of clear cell-type carcinomas and schwannomas, and neurofibromas, even when the only specimens available are from aspiration cytology.     

Primary malignant melanoma of the nasal cavity: report of two cases and review of the literature

Primary malignant melanomas of the nasal cavity are rare, as only 400 cases have been reported to date. The present paper describes two cases recently seen in Caucasian women. The authors point out the difficult clinical diagnosis, as the symptoms are rather aspecific. From the histopathological point of view, diagnosis is easy in the melanotic cases while can show interpretating problems in the amelanotic ones, when melanoma is almost indistinguishable from other malignant neoplasms. A correlation between histological grading and prognosis was not detected, as both cases showed local recurrences within one year after surgery although they were, respectively, of epithelioid and undifferentiated type. While surgery appears to be the choice treatment of the primary lesion, the treatment of cervical metastasis is still disputable. On the whole, most authors think that the role played by radio- and mainly chemo-therapy is still limited and that cervical adenopathies should be treated by a simple lympho-adenectomy rather than by a neck dissection.     

Cytopathology and diagnostics of Warthin's tumour

Warthin's tumour (WT) is a benign epithelial salivary tumour, one type of salivary adenoma. Histologically, WT is structured of two components, epithelial tissue that often lines cystic formations and lymphoid tissue in the tumour stroma. FNA is a reliable diagnostic approach in the diagnosis of salivary gland lesions allowing a highly accurate categorization of benign tumour‐like lesions, benign tumours and malignant tumours. In the proposed Milan reporting system of salivary gland lesions, WT is categorized in the IVA group of benign neoplasms. Accurate cytological diagnosis is straightforward when three characteristic components are present: oncocytes, either isolated or associated in clusters, lymphocytes and lymphoid cells and often an inflammatory/necrotic‐like substance. Also, specific features of scintigraphy and radiological imaging contribute to the diagnosis of WT. WT is categorized according to Seifert G. et al in 4 types, depending on the proportions of the epithelial component and lymphoid stroma. Differential cytopathological and pathohistological diagnosis include other salivary gland lesions with lymphoid, oncocytic epithelial and cystic components. In some cases, such as the metaplastic WT variant, there are additional cytopathological and histological diagnostic difficulties. Moreover, bilateral, multicentric or multiple and infrequently seen extra‐salivary localizations of WT are associated with further cytopathological diagnostic difficulties. Also, a rare possibility of malignant transformation of the epithelial or lymphoid component of WT as well as possible association with other primary tumours remains a challenge in accurate cytopathological and histological diagnosis of WT.     

Diagnostic cytologic features of an epididymal melanotic neuroectodermal tumor of infancy present in scrotal fluid: a case report

BACKGROUND: The cytologic features of melanotic neuroectodermal tumor of infancy (MNTI) have been described in rare cases only, and these reports have been based solely on direct smears obtained from aspirated tumor material or from touch preparations of resected tumors. CASE: We report, to our knowledge, the first documented case of an epididymal MNTI diagnosed from aspirated hydrocele fluid processed using the ThinPrep system (Cytyc Corp., Boxborough, Massachusetts, U.S.A.). CONCLUSION: Based on a 15 year retrospective review of scrotal fluids submitted for cytologic evaluation to our laboratory, MNTI represented the sole neoplasm that was represented in the fluid and could be specifically diagnosed. Compared to the direct smear evaluation in our case and other published reports, the ThinPrep method enables the recognition of both neuroblast-like cells and larger melanin-containing epithelial cells in scrotal fluid, thereby aiding in the specific diagnosis of MNTI and minimizing the risk of misdiagnosing this tumor as a more aggressive neoplasm.     

Diagnosis of thymoma by needle biopsy.

One cutting needle biopsy specimen and six fine needle aspiration biopsy specimens of thymomas were studied in order to define diagnostic criteria for this entity in biopsy material. Two of the cases demonstrated a mixed pattern of epithelial cells and lymphocytes while epithelial cells predominated in four cases and lymphocytes in one. Tumors composed of a conspicuous admixture of benign-appearing epithelial cells and mature lymphocytes were easily diagnosed. Neoplasms composed primarily of one cell type also displayed distinctive cytologic features that correlated with the histopathologic appearance of the resected tumors and permitted a diagnosis. Immunocytochemical demonstration of keratin and T6 proved useful in confirming the biphasic pattern of epithelial cells and cortical thymocytes that is characteristic of thymoma.     

Diagnosis of pulmonary hamartoma by fine needle biopsy

OBJECTIVE: To review the features of pulmonary hamartoma (PH) on fine needle biopsy (FNB), with emphasis on features that allow specific diagnosis. STUDY DESIGN: Fourteen cases of PH diagnosed on FNB were reviewed. The presence and volume of aspirate components were recorded. Attention was paid to features that might lead to false positive diagnosis of malignancy. Immunohistochemical staining for S100 was performed on cell block material. RESULTS: Fibromyxoid stroma and chondroid material were seen in 93% and 79% of cases, respectively; 71% demonstrated both components. Fibromyxoid stroma was prominent in the majority of cases; chondroid material was less abundant, being scanty in over half of cases. There were no cases in which epithelial cells represented the sole prominent component, and significant epithelial atypia was not identified. S100 staining was demonstrable in all cases in which stromal material was present in the cell block. CONCLUSION: A correct specific diagnosis of pH requires identification and correct interpretation of either fibromyxoid stroma or cartilaginous material. These components may show variable appearance on smears, with a range of potential mimics and pitfalls, but specific features are recognizable. Immunohistochemical staining of stromal material with S100 may lend support to the diagnosis.     

Benign phyllodes tumour vs fibroadenoma: FNA cytological differentiation

The differential diagnosis of fibroadenomas vs phyllodes tumours by fine needle aspiration (FNA) cytology is not possible in the majority of cases. The present study aims to look at common and dissimilar features to allow differentiation, if possible. We reviewed the FNA findings of 18 histologically proven phyllodes tumours and 18 fibroadenomas, checking in each case the epithelial features, the stromal features, and any atypia. Using a semi-quantitative score assessed by two observers we were able in most cases to distinguish a phyllodes tumour from a fibroadenoma. The most important criteria were larger stromal fragments, numerous plump stromal bare nuclei, and the higher ratio of stromal bare nuclei to epithelial bare nuclei in phyllodes tumours. In the present study, an original diagnosis of phyllodes tumour was made in 7/18 (38.9%) cases but with our criteria this could be improved to 15/18 (83.3%) cases. Therefore, the presence of specific stromal features in a dimorphic cellular pattern should suggest the correct diagnosis and differentiate its appearance from a cellular fibroadenoma.     

HIV-1 (p24)-positive multinucleated giant cells in HIV-associated lymphoepithelial lesion of the parotid gland. A report of two cases

BACKGROUND: Cystic benign lymphoepithelial lesion (CBLL) is a well-recognized parotid disorder the diagnosis of which can be made on the basis of clinical findings, human immunodeficiency virus (HIV) testing, image studies and fine needle aspiration (FNA). Most aspirations are cystic, and the lesion can be recognized if the triad of foamy macrophages, lymphoid and epithelial (squamous) cells is observed. CASES: The authors recently observed FNA cytologic features of two HIV-associated cases that exhibited numerous multinucleated giant cells (MGCs) but failed to show the epithelial component. A subsequent surgical resection was performed in one patient. Similarly to what has been described for nasopharyngeal (adenoid and tonsil) lymphoid tissue of HIV-positive patients, intense immunoexpression of S-100 and p24 (HIV-1) protein was present in MGC. CONCLUSION: The diagnosis of HIV-associated CBLL should always be considered if a parotid cystic lesion presents with numerous MGCs. Immunocytochemical detection of p24 (HIV-1) protein in MGC becomes a very useful diagnostic aid and extends to parotid CBLL many of those pathogenic features of HIV-1 infection already noted in other HIV-1-infected, lymphoid oropharyngeal lesions.     

The seminal receptacle and sperm storage in Cochlostoma montanum (Issel) (Gastropoda: Prosobranchia)

Females of Cochlostoma montanum (Prosobranchia, Cochlostomatidae) have a seminal receptacle which is not a separate diverticulum of the oviduct. The seminal receptacle derives from a differentiated portion of the renal oviduct which has an inner wall composed of only one layer of cells. These cells are of two different types, both actively involved in secretory activity. One type is represented by goblet cells filled with large vesicles containing an electron-dense, homogeneous, and partially paracrystalline material. This material is expelled into the lumen through macro-apocrine or holocrine types of secretion. The other type is represented by ciliated cells rich in small vesicles containing granular material. Probably neither kind of secretion has a nutritive function; rather they serve as matrix for spermatozoa that immobilize them and prevent their expulsion from the receptacular portion of the oviduct. Spermatozoa are inserted in invaginations of the apex of both these epithelial cells. The sperm plasma membrane covering the acrosome forms long digitations which expand toward the corresponding invaginations of the receptaculum cells. This type of adhesion is a novelty for Mollusca and resembles that in seminal receptacles of some Annelida.     

Intranuclear cytoplasmic inclusions in aspirates of follicular neoplasms of the thyroid. A report of two cases

Two cases are reviewed in which the presence of intranuclear cytoplasmic inclusions in fine needle aspiration biopsy specimens of the thyroid suggested a diagnosis of papillary carcinoma. Subsequent surgical specimens were consistent with diagnoses of microfollicular adenoma and follicular carcinoma. These cases suggest that the presence of intranuclear inclusions in epithelial thyroid cells is not limited to papillary and medullary carcinoma, as some authors have suggested.     

Malignant tumors of the stomach: apropos of 583 anatomo-clinical cases

A retrospective study interesting 582 anatomoclinical cases of gastric malignant tumors was realised in two anatomo-pathological services of Tunis from 1970 to 1985. The average age of patients is 55 years old, with extensive ranges from 17 to 85 years old. The authors point out significative male predominance 64.6% of cases. The ulcered form is the most frequent, about 3.8% of macroscopic aspect cases. Among these last, the authors find 26.7% of ulcerating and polypoid form with invasive characteristics, and 18.83% of linitis plastica. The pyloric area localisation is the most frequent, 68% of cases. Diffuse tumors are observed in 8.47% of cases and numerous stomach localisation in 0.82% of cases. 84% of histological aspect are represented by adenocarcinoma, the most frequent of them (35%) is well differentiated type, then the poorly differentiated (20%) and atypic form (19.75%). Frequency of lymphosarcoma reaches 14.7%, the first is the centroblastic form, then lymphoblastic and lymphoplasmocytic forms. Concerning evolution, gastric cancer is an infiltrative tumor: serosal surface is attempted in 69.5% of cases, and during the first chirurgical act half cases show lymph nodes metastasis.     

Kyste de la vésicule séminale associé à une agénésie rénale homolatérale: à propos de trois observations

The combination of seminal vesicle cyst and homolateral renal agenesis is a rare congenital anomaly. However, this anomaly is diagnosed more frequently due to progress in medical imaging. The authors report three cases of seminal vesicle cyst associated with ipsilateral renal agenesis in two cases and ectopic ureter in one case. All cases presented nonspecific clinical symptoms. The diagnosis was suspected on imaging (ultrasound and computed tomography). Treatment was surgical in two cases and endoscopie in one case. The authors review the literature on the aetiology and pathogenesis of seminal vesicle cyst, its association with homolateral renal agenesis and diagnostic and therapeutic methods.     

Cystic degeneration in phyllodes tumor. A source of error in cytologic interpretation

OBJECTIVE: To examine problems encountered in the cytologic interpretation of phyllodes tumor (PT) with cystic degeneration and solutions thereof. STUDY DESIGN: Cystic degeneration was found in seven PTs (five benign, one low grade and one high grade). Aspirates from these yielded fluid and were usually labelled fibrocystic change on the original cytology. Smears were retrospectively analyzed, with special attention to the background, presence and nature of the epithelial and stromal fragments, foam cells and naked nuclei in the background. RESULTS: PTs with cystic degeneration on cytology showed thick fluid in the background, foamy macrophages (100%), apocrine cells (28%) and epithelial fragments, which showed nuclear atypia in two cases. On reviewing the smears, five of seven PTs had stromal fragments, albeit in small numbers. Most important, even in the absence of stromal fragments, all cases showed 5-50% naked nuclei of the fibroblastic type dispersed within the fluid background. CONCLUSION: In cases of fluid aspirates from well-defined lumps, one must search for fibroblastlike naked nuclei or stromal fragments within the fluid to clinch the diagnosis of phyllodes tumor.     

Improving the sensitivity of cervical cytologic screening. A comparison of duplicate smears and colposcopic examination of patients with cytologic inflammatory epithelial changes

During a ten-month period, 264 cervical cytologic specimens were submitted in duplicate to two separate cytology laboratories. An attempt was made to perform colposcopy on all 45 patients reported as having an abnormality by either laboratory. All but one patient with a cytologic diagnosis of cervical intraepithelial neoplasia (CIN) underwent colposcopy, as did 68% of the patients with a diagnosis of nondysplastic atypia (inflammatory epithelial changes [IEC]). Five cases of histologically verified CIN were found by colposcopic study of patients with a cytologic diagnosis of CIN; two additional cases were found by colposcopic study of patients with a cytologic diagnosis of IEC. On the assumption that patients not colposcoped were not systematically different from the others with IEC, the screening sensitivities for both laboratories and for cytology followed by colposcopy of IEC cases were estimated. A statistically significant improvement in screening sensitivity was achieved by colposcopic examination of patients with IEC. This conclusion was tempered by a Bayesian analysis that suggested that some of the apparent improved sensitivity could be due to falsely positive biopsy reports. Despite potential benefits, it is premature to recommend universal colposcopic examination of patients with cytologic reports of inflammatory epithelial changes.     

Merkel cell (small cell) carcinoma of the skin: Immunohistochemical and ultrastructural demonstration of distinctive perinuclear cytokeratin aggregates and a possible association with B cell neoplasms

Summary Three cases of Merkel cell (small cell) carcinoma of the skin are presented with immunohistochemistry for epithelial and neuroendocrine antigens. All three cases showed distinctive punctate perinuclear cytoplasmic positivity for cytokeratin which corresponded to aggregates of intermediate filaments, seen ultrastructurally in two cases. Epithelial membrane antigen was also identified in two cases. Only one case showed cytoplasmic positivity for neuron specific enolase, and immunostaining for a battery of polypeptide hormones was negative. The demonstration of cytokeratin perinuclear inclusions provides a distinctive immunohistochemical feature to aid in their diagnosis. Two of the three patients had chronic lymphocytic leukaemia years before the diagnosis of Merkel cell carcinoma. The possible association of lymphoproliferative disorders, particularly B cell tumours, and Merkel cell carcinoma is discussed.     

Exploiting the "toothpick effect" of the Cytobrush by plastic embedding of cervical samples

The introduction of the combined spatula-Cytobrush sampling method has increased the diagnostic accuracy of cervical cytology. However, the smears from a small number of cases contained epithelial fragments dislodged by the "toothpick effect" of the Cytobrush. Due to their thickness, these epithelial fragments in the smears are very difficult (if not impossible) to scrutinize and are thus undiagnosable. The presence of only such fragments in smears led to false-negative diagnoses in two cases of invasive carcinoma. To solve this problem, these epithelial fragments were embedded in plastic, with thin sections prepared from the blocks. This paper presents the morphologic features and diagnostic accuracy of 77 such problem cases (found among 50,000 cases with spatula-Cytobrush smears) to which this method was applied. In almost all cases, the diagnosis on the plastic-embedded sections matched the diagnosis on the colposcopically directed biopsy. Of these 77 patients, the biopsy diagnosis showed 5 severe dysplasias, 6 carcinomas in situ, 1 squamous-cell carcinoma, 2 adenocarcinomas in situ and 2 adenocarcinomas. In addition, data are presented concerning the nuclear-size and shape-factor differences in smears versus plastic-embedded sections, and the stereologic consequences of smearing and cutting these epithelial fragments are discussed. These plastic-embedded sections are well suited for use in quantitative microscopy, as well as for diagnostic purposes.     

Two cases of nevoid basal cell carcinoma syndrome

Motivated by the diagnosis and treatment of two cases of nevoid or Goltz-Gorlin syndrome, we have taken a brief look at the literature and present these two cases, which display the four principal features defining this syndrome: multiple basal cell carcinomas, maxillary cysts, skeletal anomalies, and ectopic calcifications. Certain aspects are emphasized, including the association in one of them of basal cell carcinomas with a cystic adenoma or Brooke's tumor, which, although described by other authors, is infrequent.     

Fine needle aspiration cytology of basal cell adenoma of the salivary gland: a cytohistological correlation study of 35 cases

B. Vicandi, J.A. Jiménez‐Heffernan, P. López‐Ferrer, P. González‐Peramato, M. Patrón and J.M. Viguer
Fine needle aspiration cytology of basal cell adenoma of the salivary gland: a cytohistological correlation study of 35 cases Objective: In order to evaluate the possibility of a specific cytological recognition of basal cell adenoma (BCA) we reviewed our experience with 35 histologically proven cases. Few series describing cytological features of BCA are available and diagnostic cytological criteria are not well established. Methods: This study was based on 41 cytology samples from 35 patients with BCA. Thirty‐five aspiration procedures were performed pre‐operatively and six on tumour recurrence. Nineteen of the 35 patients were men and 16 women. The mean age at diagnosis was 55 years old (range 24–92). The series includes one non‐representative case. Except for one tumour located in the upper lip, all of them involved the parotid gland. Results: Aspirates were cellular, showing groups with dense, homogeneous metachromatic stroma and single cells. Relevant features were the trident‐like configuration of groups, intimate relationship between neoplastic cells and stroma and cellular polymorphism. In approximately half of the cases a precise diagnosis was given. Most of the remaining tumours were diagnosed as benign but they were difficult to differentiate from pleomorphic adenoma. Regarding malignancy, there were two misdiagnoses of acinic cell carcinoma, due to high epithelial cellularity along with scarcity of stroma, and one case was considered to be suspicious of malignancy. Conclusion: BCA shows characteristic cytological features that allow a precise diagnosis. The main differential diagnosis is epithelial‐rich pleomorphic adenoma, while acinic cell carcinoma is a potential false positive.     

Fine needle aspiration cytology of malignant mesothelioma

The results of fine needle aspiration (FNA) cytology in 19 cases of malignant mesothelioma are presented. Adequate material for a diagnosis of malignancy was obtained in 17 cases, and in 8 cases a specific diagnosis of mesothelioma could be made. In four other cases, the findings were either consistent with or suggestive of mesothelioma; in four, accurate distinction from other neoplasms was not possible, and in two cases, adenocarcinoma was suggested. The spectrum of cytologic findings ranged from neoplasms of purely epithelial appearance through more pleomorphic biphasic neoplasms to anaplastic tumors. A combination of epithelial-like cell clusters, pavement-like sheets of epithelial cells with well-defined cell borders and prominent cell separation, dispersed angular cells with dense cytoplasm and some spindle-cell forms was the most specific cytologic pattern for mesothelioma. In four neoplasms, ultrastructural examination of aspirated material provided the additional evidence for a definitive diagnosis. The identification of hyaluronic acid within intracytoplasmic vacuoles, either in smears or in cell blocks, confirmed the diagnosis in three tumors. Only in one case, with a strong clinical background suggesting mesothelioma, was the cytologic preparation sufficient for diagnosis without ancillary diagnostic methods. FNA is of particular value in the diagnosis of pleural mesothelioma in patients who do not present with a pleural effusion. Obtaining material for cell block preparations, cytochemistry or ultrastructural study is generally necessary for definitive tumor typing.