Pitfalls in the diagnosis of Wegener''s granulomatosis on fine needle aspiration cytology

OBJECTIVE: To review the clinical and pathological findings in six suspected cases of Wegener's granulomatosis (WG) and highlight the diagnostic difficulties faced by the cytopathologist. METHODS: Retrospective review of records of the Cytopathology Department to identify patients who underwent image-guided transthoracic pulmonary fine needle aspiration cytology (FNAC) for pulmonary lesions of suspected WG and those who were subsequently confirmed to have WG. Detailed evaluation of cytomorphological features was carried out. RESULTS: A total of six cases were identified in whom the initial procedure to obtain a pathological diagnosis was transthoracic FNAC. In one case, atypical squamous cells on cytology initially suggested a diagnosis of squamous cell carcinoma while in another a diagnosis of WG was made on cytology; however, a subsequent lung biopsy revealed silicosis. CONCLUSION: Acute inflammation and necrosis are the most consistent cytopathological findings in WG. In selected cases FNAC can provide supportive pathological evidence to establish a diagnosis of WG.     

Granulomatous inflammation of the breast in a pregnant woman: report of a case with fine needle aspiration diagnosis

BACKGROUND: Granulomatous inflammation of the breast is an inflammatory process with multiple etiologies. It can accompany breast carcinoma or be idiopathic. It often presents clinically in a fashion mimicking carcinoma. Idiopathic granulomatous mastitis is strongly associated with lactation and is reported to occur in postpartum patients. This is the second fine needle aspiration (FNA) report of idiopathic granulomatous inflammation in the breast of a pregnant woman. CASE: A 27-year-old, 7-month-pregnant woman presented with a hard nodule in her right breast; on ultrasound examination it showed mixed echogenicity, suspicious for carcinoma. FNA showed granulomatous inflammation. The smears were highly cellular, with many clusters of and single epithelioid cells displaying moderate pleomorphism and prominent nucleoli in a background composed of neutrophils, plasma cells, lymphocytes and multinucleated cells. Core needle biopsy revealed a nonnecrotizing, granulomatous lesion. CONCLUSION: The diagnosis of granulomatous inflammation can be challenging, and the cytologic features can be difficult to separate from those of carcinoma. The relatively rare occurrence of this lesion and its cytologic features make it a potentially difficult diagnosis and diagnostic pitfall.     

Fine needle aspiration cytology of renal infarcts. Cytomorphologic findings and potential diagnostic pitfalls in two cases

The fine needle aspiration (FNA) cytologic features of two cases of renal infarction are presented. Both patients did not have a classic clinical history for infarction, and the radiologic findings were suggestive of neoplasia. In one of our cases, necrotic glomeruli and tubules were present, which suggested the correct diagnosis of renal infarction and permitted appropriate early treatment. In the other case, groups of atypical renal tubular cells undergoing repair secondary to the infarction was misinterpreted as renal cell carcinoma. This case illustrates that renal infarction, like pulmonary infarction, can be a potential pitfall for a false-positive cytologic diagnosis of malignancy in FNA biopsy. A conservative approach is warranted when there is scanty cellularity and atypical cells having features of a repairlike reaction are present.     

Pitfalls in the diagnosis of herpes simplex infection in respiratory cytology

OBJECTIVE: To evaluate the prevalence and potential pitfalls in making an accurate diagnosis of respiratory herpetic infection. STUDY DESIGN: Eighteen cases with the diagnosis of herpes simplex virus (HSV) infection were identified from a total of 7,501 (0.24%) respiratory specimens. All cases were evaluated for classic cytomorphologic features of HSV infection and associated cytologic findings. The parameters studied included number of cells with HSV cytopathic effect, intranuclear inclusions, multinucleation, presence of atypical squamous cells, reparative changes, presence and degree of inflammation and associated obscuring factors. RESULTS: Only a minority of cases (28%) had numerous cells with classic viral cytopathic change. Four (22%) of 18 cases showed atypical squamous cells, and 5 (28%) revealed reparative changes. The majority of the cases were associated with inflammation, which was severe in 4 cases (22%). Blood and degenerative changes obscured the cytologic findings in 3 cases (17%). One case showed a necrotic background. CONCLUSION: Due to the low prevalence of HSV infection in respiratory cytology, a high index of suspicion is necessary for an HSV diagnosis. Pitfalls for a false negative diagnosis include limited number of cells with viral cytopathic change, only mononuclear cells with viral changes and obscuring inflammation or blood. Pitfalls for a false positive diagnosis of malignancy include atypical keratinized squamous cells, atypical repair, cellular degeneration and necrotic background.     

Cytology of basaloid squamous carcinoma of the bronchus. A case report

BACKGROUND: The cytologic appearance of basaloid squamous carcinoma (BSC) arising in the lower respiratory tract has not been described very well because of its rarity. This article describes a surgical case of bronchial BSC and provides the first documentation of the sputum and imprint cytologic features of the tumor. CASE: A 74-year-old man presented with hemoptysis. An abnormal intrabronchial mass was revealed by computed tomography and bronchoscopy. Preoperative cytology and biopsy showed that the mass was composed of small, round, atypical cells, but correct diagnosis was difficult. Under a tentative diagnosis of small round cell carcinoma, a right lobectomy was performed. The resected tumor was composed of small cells showing peripheral palisading and partial epidermoid differentiation. There was no glandular differentiation. Focal necrosis was also noted. Immunohistochemical markers for smooth muscle and neuroendocrine cells were negative. The tumor was eventually diagnosed as BSC or basaloid carcinoma (BC) with squamous differentiation. CONCLUSION: It is important to recognize this disease, especially when undetermined small round cell carcinoma is noted in cytologic specimens, in order to properly assess prognosis. Cytologic detection of nuclear palisading of the neoplastic cells, one of the hallmarks of the disease, may be difficult, however, careful examination to reveal neoplastic cells showing squamous differentiation appears helpful for diagnosis.     

Cytology of primary pulmonary mucoepidermoid and adenoid cystic carcinoma. A report of four cases

BACKGROUND: Mucoepidermoid and adenoid cystic carcinomas are very rare primary pulmonary neoplasms that can be classified under the broader heading of salivary gland-like neoplasms (SGN). Both entities need to be considered in the cytologic differential diagnosis of lung tumors. We reviewed cytologic findings in primary pulmonary neoplasms diagnosed at our institution during the time period 1981 to the present along with outside consultation cases. CASES: Three cases of primary mucoepidermoid carcinoma and one case of primary adenoid cystic carcinoma of the lung were diagnosed based on cytology during the period examined. Patient ages were 16, 25, 47 and 78 years, respectively. The mucoepidermoid cytology specimens were composed of three cell types, mucinous, squamous and intermediate cells, at times associated with extracellular mucin. The adenoid cystic carcinoma consisted of small, uniform cells with dark nuclei, scant cytoplasm and associated, acellular balls of basement membrane material. CONCLUSION: The differential diagnosis for primary pulmonary neoplasms needs to include the rare SGN. Cytologic features of adenoid cystic carcinoma are diagnostic; those of mucoepidermoid carcinoma are at least suggestive.     

Staphylococcus aureus and Wegener's granulomatosis

Wegener's granulomatosis (WG) is a form of systemic vasculitis. It is characterized by granulomatous inflammation in the upper and lower airways, vasculitis and necrotizing glomerulonephritis, and is strongly associated with antineutrophil cytoplasmic antibodies against proteinase 3. Since the etiology of the disease is not clear, treatment, consisting of corticosteroids and immunosuppressives, is nonspecific and associated with severe side effects. Pinpointing the trigger(s) of the disease would highly improve treatment. Clinical evidence shows that an infectious agent, the bacterium Staphylococcus aureus, is a risk factor for disease relapse, suggesting its involvement in the pathogenesis of WG. Here we review both clinical and experimental data that either indicate or support a role for S. aureus in WG.     

Staphylococcus aureus and Wegener's granulomatosis

Wegener's granulomatosis (WG) is a form of systemic vasculitis. It is characterized by granulomatous inflammation in the upper and lower airways, vasculitis and necrotizing glomerulonephritis, and is strongly associated with antineutrophil cytoplasmic antibodies against proteinase 3. Since the etiology of the disease is not clear, treatment, consisting of corticosteroids and immunosuppressives, is nonspecific and associated with severe side effects. Pinpointing the trigger(s) of the disease would highly improve treatment. Clinical evidence shows that an infectious agent, the bacterium Staphylococcus aureus, is a risk factor for disease relapse, suggesting its involvement in the pathogenesis of WG. Here we review both clinical and experimental data that either indicate or support a role for S. aureus in WG.     

Exfoliative cytology of a lymphoepithelioma-like carcinoma in a cervical smear. A case report

BACKGROUND: Lymphoepithelioma-like carcinoma of the cervix (LELC) is cytologically identical to its counterparts at other sites, such as the nasopharynx. LELC can be suspected on a cervical cytologic smear. The differential diagnosis includes nonkeratinizing squamous cell carcinoma with prominent stromal inflammation, carcinoma with intense stromal eosinophilia, glassy cell carcinoma, malignant lymphoma (especially lymphoepitheloid-Lennerts lymphoma) and metastatic Schmincke-Regaud tumor. CASE: A 55-year-old female presented with an ulcerated endophytic tumor in the cervix. Exfoliative cytology showed uniform, large tumor cells, often associated with inflammatory cells, with round or oval nuclei and one or more prominent nucleoli. The cytoplasm was finely granular to flocculent, and the nuclei were uniformly vesicular. The chromatin was peripherally marginated. The cell borders were indistinct. There was no evidence of dyskeratotic or keratinized cells, koilocytes or glandlike formations. These findings were highly suspicious for LELC and were confirmed by biopsy. Flow cytometry showed DNA aneuploidy, with a DNA index of 1.08. In situ hybridization was negative for human papillomavirus 16 and 18. CONCLUSION: LELC of the uterine cervix has cytologic features that are sufficiently characteristic for a specific cytologic diagnosis. The diagnosis, nevertheless, has to be proven by histology.     

Aspiration cytology of the conjunctival surface

OBJECTIVE: To evaluate a method of obtaining conjunctival cells that utilizes aspiration of the conjunctival surface. STUDY DESIGN: Eighteen eyes from 16 patients with epibulbar lesions underwent aspiration of the conjunctival surface using a tuberculin syringe without a needle. The aspirated cells were prepared by the cytocentrifuge or Millipore filter technique. The lesions were subsequently biopsied, and the cytologic and histologic diagnoses were compared. RESULTS: Diagnoses of the conjunctival lesions, in decreasing order of frequency, were conjunctival intraepithelial neoplasia (dysplasia, carcinoma in situ), squamous cell carcinoma, squamous metaplasia, nevus, lymphoma and inflammation. In this feasibility study, the cytologic diagnosis accurately correlated with the histologic diagnosis in most cases. There were two cases in which the cytologic diagnosis led to the correct histologic diagnosis. CONCLUSION: Aspiration cytology of the conjunctival surface is useful in obtaining diagnostic material and may be used as a guide to where a biopsy should be performed. Limitations include inadequate samples and lack of observer experience.     

Rare coexistence of keratinizing squamous metaplasia with xanthogranulomatous pyelonephritis. Report of a case with the role of immunocytochemistry in the differential diagnosis

BACKGROUND: Xanthogranulomatous pyelonephritis (XPN), a rare form ofchronicpyelonephritis, is commonly associated with lithiasis and rarely leads to keratinizing squamous metaplasia. Its manifestations closely mimic those of a renal neoplasm, leading to misdiagnosis of malignancy, often resulting in radical nephrectomy. The role of immunocytochemistry in the preoperative cytologic diagnosis is assessed in the present case report. CASE: A 20-year-old male presented with fever and an enlarging mass in the right renal angle. Ultrasonography revealed a heterogeneous mass in the renal pelvis. Fine needle aspiration cytology was advised to rule out malignancy. Aspiration smears from the mass showed many dissociated cells and clusters of them with abundant vacuolated cytoplasm, vesicular nuclei and prominent nucleoli in some cells. Many desquamated metaplastic squamous cells were also seen. The background was predominantly necrotic, with inflammatory cells. The cytologic possibility of XPN with squamous metaplasia vs. renal cell carcinoma was considered. Immunocytochemical markers, epithelial membrane antigen (EMA) and CD68 (histiocytic marker) were used to determine the nature of the suspicious vacuolated cells; these cells were immunoreactive for CD68 and negative for EMA, thus confirming the cytologic diagnosis of XPN with keratinizing squamous metaplasia. CONCLUSION: The case highlights the presence of metaplastic squamous cells in XPN in smears for the first time. Immunocytochemistry is an essential tool in the preoperative cytologic diagnosis of XPN. The patient can be managed conservatively with antibiotics.     

Idiopathic granulomatous mastitis. Report of a case diagnosed with fine needle aspiration cytology.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a benign, inflammatory breast disease of unknown etiology. Although it is rare, it frequently presents in a manner similar to that of breast carcinoma. CASE: A 41-year-old female developed unilateral idiopathic granulomatous mastitis, diagnosed by fine needle aspiration cytology. The clinical presentation and mammographic findings were suspicious for carcinoma. Fine needle aspiration cytology showed granulomatous inflammation. Histopathologic examination revealed a noncaseating, granulomatous lesion. Further clinical, radiologic and laboratory investigations disclosed no etiology. Therefore, we considered the case to be idiopathic granulomatous mastitis. CONCLUSION: Cytologically it may be difficult to distinguish IGM from carcinoma of the breast. Typical cytologic findings of the lesion are helpful to rule out cancer. In the differential diagnosis, all known causes of granulomatous changes have to be excluded before a diagnosis of idiopathic granulomatous mastitis is made.     

The application of visual cell profiles in the study of premalignant atypias in sputum

Because the diagnosis of squamous-cell carcinoma of the lung by routine cytologic screening of sputum is often inconclusive, our laboratory is studying the use of cytomorphologic profiles as a reliable diagnostic aid. This study reports the analysis of the profiles of 75 subjects, both cigarette-smoking volunteers and hospitalized patients suspect for lung cancer. Twenty-five of the subjects had been classified as having squamous metaplasia, 25 as having atypias and 25 as having squamous-cell carcinoma. Four slides were made for each subject, with 100 random fields viewed on each slide. The frequency of free alveolar macrophages, metaplastic squamous cells, epithelial atypical cells and malignant squamous cells were noted for each field. The results indicated that, although there were large differences between individual profiles within each diagnostic category, there were significant differences between the average profiles for each diagnostic category. Furthermore, although there were differences in cell frequencies from slide to slide and within slides, the differences were constant across diagnostic categories. The results are supportive of the progressive-atypia hypothesis for squamous-cell carcinoma of the lung and provide a baseline for comparison with subsequent individual profiles.     

Fine needle aspiration cytology of subareolar abscess of the breast. Spectrum of cytomorphologic findings and potential diagnostic pitfalls

The cytomorphologic findings of eight cases of subareolar abscess of the breast diagnosed by fine needle aspiration (FNA) biopsy are presented. A spectrum of cytologic findings was appreciated, including diagnostic anucleated squames associated with numerous neutrophils, keratinous debris, cholesterol crystals, parakeratosis and strips of squamous epithelium. A foreign-body reaction, with sheets of histiocytes and multinucleated foreign-body-type giant cells, was noted in some of the cases. Potential pitfalls for a false-positive diagnosis of malignancy included the presence of groups of atypical ductal cells, squamous atypia and fragments of exuberant granulation tissue. Seven of the eight cases had complete surgical excision of the lesion, which demonstrated the characteristic findings of dilated lactiferous ducts undergoing squamous metaplasia with rupture and surrounding extensive acute and chronic inflammation with foreign-body reaction. With recognition of the FNA cytologic findings of subareolar abscess of the breast, a specific diagnosis can be rendered, which then allows different treatment modalities depending on the stage of the lesion. Appreciation of the spectrum of cytologic features will enable the pathologist to make the correct diagnosis and thereby avoid potential pitfalls that can possibly lead to a false-positive diagnosis of malignancy.     

Mycosis fungoides with pulmonary involvement. Cytopathologic findings

In order to define the cytologic features of pulmonary involvement by mycosis fungoides, 15 respiratory cytology specimens from four patients with biopsy-proven pulmonary mycosis fungoides were reviewed. The presence in sputum smears of occasional small or large cerebriform mononucleated cells against a background of numerous atypical lymphocytic cells permitted an antemortem cytologic diagnosis of probable or definite dissemination of mycosis fungoides with pulmonary involvement. Similar cells were seen in aspiration smears. The lymphocytic infiltrates were similar to those in corresponding skin biopsies in each case. The distinctive cytologic findings in these cases may therefore help to determine the underlying etiology of pulmonary lesions and may contribute to the antemortem diagnosis of visceral dissemination of mycosis fungoides.     

Clinical utility of fine needle aspiration biopsy in the diagnosis of Wegener's granulomatosis. A report of two cases.

In two patients, pulmonary lesions of Wegener's granulomatosis (WG) were sampled by fine needle aspiration biopsy: one with the clinical diagnosis of primary pulmonary malignancy and the other with a clinical suspicion of WG. In the latter case the smears showed distinctive eosinophilic, collagen necrosis (pathergic necrosis), poorly formed granulomata composed of loose aggregates of elongated, often palisading epithelioid histiocytes, and multinucleate histiocytes. A cell block preparation in this case contained minute tissue fragments illustrating the distinctive, pathergic-type necrosis. In the former case, many of these features were present, but additionally there were several groups, atypical bronchial epithelial cells that, in light of the clinical impression, initially led to an incorrect diagnosis of bronchoalveolar carcinoma. Subsequent review of this case led to the diagnosis of WG. Antineutrophil cytoplasmic antibody (ANCA) serology was later obtained, confirming the diagnosis of WG in both cases. In our experience, the cytomorphologic findings of granular collagen necrosis, granulomata and multinucleate cells, although not specific, should alert the cytopathologist to consider the diagnosis of WG, especially when special stains for microorganisms are negative. A recommendation for ANCA serology testing early in the disease process, particularly in the limited forms of the disease, may lead to early recognition of WG, resulting in prompt institution of immunosuppressive therapy, greatly improving the patient's prognosis.     

Glassy cell carcinoma of the uterine cervix. Report of a case with cytohistologic and immunohistochemical study

BACKGROUND: Glassy cell carcinomas of the uterine cervix are poorly differentiated carcinomas composed of cells with a large, round to oval nucleus containing one or multiple prominent nucleoli, finely vacuolated eosinophilic to amphophilic cytoplasm and distinct cell borders. These cells occur in sheets and chords, with fibrovascular septae presenting a mixed inflammatory infiltrate. This neoplasm has a poor response to radiotherapy and a worse prognosis than the usual types of adenocarcinoma and squamous cell carcinoma. There are few reports on the cytologic and histopathologic features of this neoplasm. CASE: A 56-year-old woman presented with a large, exophytic cervical tumor. Exfoliative cytology showed clusters of cells and single cells with large, round to oval nuclei, with one or multiple nucleoli and moderate to large, finely granulated cytoplasm with distinct cell borders. The background of the smears had a polymorphous inflammatory infiltrate, necrotic debris and proteinaceous material. A high mitotic rate was observed, as were rare bizarre and atypical multinucleated cells. There was no evidence of koilocytes. These findings were highly suggestive of glassy cell carcinoma and were confirmed by the histologic and immunocytochemical findings, with positivity for cytokeratin (MNF116), vimentin and carcinoembryonic antigen and negativity for HMB-45. CONCLUSION: Glassy cell carcinoma of the cervix presents a cytologic picture that can be highly suggestive of the diagnosis in typical cases; however, in difficult cases ancillary techniques, such as immunocytochemistry, as well as histologic findings might confirm the diagnosis.     

Fine needle aspiration cytologic diagnosis of focal intrahepatic extramedullary hematopoiesis

A computed tomographic scan in an 80-year-old man with a urinary obstruction demonstrated a solitary space-occupying liver lesion, which was clinically suspected to be a metastatic carcinoma. Fine needle aspiration (FNA) of the mass produced a smear containing atypical, possibly malignant, cells. Correlation of the FNA findings with the patient's history resulted in a cytologic diagnosis of an intrahepatic focus of extramedullary hematopoiesis (EMH). This case shows FNA biopsy to be a reliable method of diagnosing foci of EMH, but also demonstrates the potential pitfall of diagnosing atypical megakaryocytes as malignant in FNA smears. EMH should be considered in the differential diagnosis of patients with bone marrow disorders and mass lesions in extramedullary sites.     

Immunohistochemical analysis of the ubiquitin-conjugating enzyme UbcH10 in lung cancer: a useful tool for diagnosis and therapy

The ubiquitin-conjugating enzyme (UbcH10) plays important roles in the regulation of cell cycle progression. Recently, UbcH10 expression has been demonstrated in several human and experimental tumors, and proteasome inhibitors have been tested in trials for pulmonary neoplasms; however, the underlying mechanisms as well as the clinicopathological relevance of UbcH10 in the genesis and progression of lung cancer remain largely unknown. Therefore, the authors evaluated the expression of UbcH10 in human lung cancer and evaluated its possible diagnostic and prognostic use. They found that most cases of lung adenocarcinoma, squamous cell carcinoma, and large cell and small cell carcinoma were positive for UbcH10. The expression levels of UbcH10 progressively increased with decreasing degree of tumor differentiation. There was a statistically significant difference of UbcH10 positivity between grade I/III of lung adenocarcinoma (p=0.013) and squamous cell carcinoma (p=0.002). No significant differences were found between histological types (p=0.072). In the case of cell blocks prepared from pleural effusions, inflammatory and reactive mesothelial elements did not show appreciable UbcH10 expression, whereas neoplastic cells exhibited clear UbcH10 positivity. The results suggest that UbcH10 might represent a new and promising diagnostic and prognostic marker in both histologic and cytologic specimens of lung cancer.     

Cytomorphology of verrucous carcinoma of the cervix. A case report

BACKGROUND: Verrucous carcinoma of the uterine cervix is rare. Cytology is thought not to be helpful in the diagnosis of this lesion due to its bland morphology. The cytologic features of this lesion remain poorly defined. CASE: The cytologic findings in a Pap smear facilitated the diagnosis of verrucous carcinoma of the cervix. The features included atypical polygonal and spindle cells with abundant, keratinizing cytoplasm; atypical squamous cells with pearl formation; and frequent, nonkoilocytic cytoplasmic vacuolization. CONCLUSION: There are 30 published reports on verrucous carcinoma involving the cervix and vagina that include the cytologic findings. In 70% of these cases, cytology was abnormal. Recognition of the cytologic characteristics may help in identifying this lesion on cytology, prevent delays in diagnosis and ensure that patients receive appropriate therapy.