Basal cell carcinoma metastatic to the salivary glands: differential diagnosis in fine-needle aspiration cytology.

A disparate group of salivary gland neoplasms is characterized by small, uniform, hyperchromatic, basaloid cells. This "small blue cell" pattern is most common in non-Warthin's types of monomorphic adenoma, or in adenoid cystic carcinoma. Small cell anaplastic carcinoma (primary or metastatic), metastatic basaloid squamous cell carcinoma, basal cell adenocarcinoma, and metastatic nasopharyngeal carcinoma are rarely encountered but may present a cytologically similar appearance. We report one female and two male patients (median age = 84 yr) with cutaneous-type basal cell carcinoma (BCC) aspirated from metastatic deposits in the parotid (2 cases) or the submandibular (1 case) gland. One was correctly classified at the time of aspiration, based on a previous history of multiple facial BCC. One was interpreted as carcinoma, the previous history being unavailable at the time of FNA. Smears in these two cases show necrosis and rare keratotic cells. The third cases was mistaken for pleomorphic adenoma (PA); the smears showed metachromatic fragments of collagenous tumor stroma that were misinterpreted as the matrix material typical PA. Similar material was identified in the other two cases. When the "small blue cell" pattern is encountered in salivary bland cytology, one should consider BCC, especially if necrosis is identified. The desmoplastic tumor stroma of BCC may mimic the chondroid matrix of PA. Careful consideration of previous history is very important.

Basal cell (monomorphic) and minimally pleomorphic adenomas of the salivary glands. Distinction from the solid (anaplastic) type of adenoid cystic carcinoma in fine-needle aspiration.

Cytologic features of the cell-stroma interface are useful in distinguishing between monomorphic adenomas of the basal cell type and adenoid cystic carcinoma. In basal cell adenomas, the collagenous stroma interdigitates with adjacent cells, whereas in adenoid cystic carcinoma, the two are separated by a sharp smooth border. Furthermore, the stroma of basal cell adenomas can contain rare spindle cells or capillaries, but the cylinders of adenoid cystic carcinoma are acellular. The authors review their experience with five cases of basal cell adenoma, and three cases that were designated "minimally pleomorphic adenomas." The latter group showed the small blue cell pattern of basal cell adenoma at the time of fine-needle aspiration, and histology revealed only small foci of typical pleomorphic adenoma. With the exception of one cystic case, the cell-stroma interface of basal cell adenoma was observed in all eight cases. These cases are contrasted with three adenoid cystic carcinomas with extensive solid (anaplastic) areas. All showed the small blue cell pattern and cell-stroma interface features of basal cell adenoma. Neither showed the smooth-bordered cylinders of adenoid cystic carcinoma. Two of these three were incorrectly interpreted as benign at the time of fine-needle aspiration. The authors suggest that the stroma aspirated from solid adenoid cystic carcinoma represents desmoplastic tumor stroma that mimics the pattern of basal cell adenoma in smear material. Distinction between basal cell adenoma and the solid type of adenoid cystic carcinoma at the time of fine-needle aspiration remains a very difficult problem.

Diagnostic difficulties in the interpretation of needle aspiration material from large renal cysts.

In recent years, fine-needle-aspiration biopsies (FNA) have been widely used in the evaluation of renal masses, with false-positive FNA data being very uncommon. We present a case report of a 76-yr-old man with a 16-cm renal cyst and what was interpreted as an isolated calcified mural nodule. Following drainage of the main cyst fluid, FNA biopsy showed atypical cell clusters thought to be positive for malignancy. Subsequent surgery failed to disclose either a residual mural nodule or evidence of malignancy. Immunoperoxidase studies performed on both the cell block and actual cyst wall suggested that the abnormal cells were histiocytes. The diagnostic pitfalls of this case, along with a review of pertinent literature, are discussed.

Infectious mononucleosis in lymphoid tissue. Histopathology, in situ hybridization, and differential diagnosis.

The histopathologic features of tissue specimens from 16 patients with acute Epstein-Barr virus-induced infectious mononucleosis, which was confirmed by clinical and serologic methods, are described. The clinical course was usually self-limited (14 patients), but it resulted in the death of two patients, one of whom (patient with renal transplantation) was immunosuppressed. Each lymphoid tissue specimen, including those obtained from the lymph nodes (n = 9), tonsils (n = 5), spleen (n = 1), and appendix (n = 1), showed a nonuniform expansion of nonfollicular areas by a polymorphous population of lymphocytes, including transformed lymphocytes and immunoblasts. In situ hybridization demonstrated Epstein-Barr virus-infected lymphocytes in four of eight tissue specimens that were studied. Other histologic features included Reed-Sternberg-like cells, plasma cells, histiocytes, frequent mitoses, abundance of postcapillary venules, and necrosis. These histologic features should suggest a diagnosis of infectious mononucleosis rather than other processes, either benign or malignant, that can mimic it.

Nodular fasciitis: spontaneous resolution following diagnosis by fine-needle aspiration.

Nodular fasciitis can be histologically mistaken for a sarcoma. Typical cases are less than 5 cm and enlarge rapidly over days or weeks before diagnosis. The natural history of nodular fasciitis is unknown, since the diagnosis is usually based on excised lesions. Fine-needle aspiration of nodular fasciitis has been described, and features benign-appearing spindle cells (singly and in groups), collagen, and myxoid material. We describe 11 cases in which nonsurgical observation led spontaneously to complete resolution. Our study includes 7 males and 4 females (24 to 73 years of age; median = 42). Lesions were located in the arm (4), thigh (3), temporal area (2), breast (1) and the parotid (1) and ranged from 0.5 to 5.0 cm. (median = 1.5). They had been present for from less than 1 to 4 weeks (median = 2). In 9 cases, spontaneous resolution occurred in from 3 to 8 weeks (median = 4). Two other patients were lost to follow-up for up to 11 months, after which resolution was noted. Small palpable masses in the subcutaneous soft tissues which evolve over a short period of time and show the cytologic features of nodular fasciitis should be managed nonsurgically. If resolution does not occur within a few weeks, surgery can then be performed.

Cellular follicular cyst of the ovary: fluid cytology mimicking malignancy.

We report three ovarian cysts studied by aspiration cytology. The fluids obtained were highly cellular, with numerous groups of atypical cells featuring a high nuclear-cytoplasmic ratio, nuclear hyperchromasia, and prominent nucleoli. In each case, these features were considered evidence of a low-grade malignant neoplasm. All three patients underwent oophorectomy, which revealed benign follicular cysts. Possible means of resolving the diagnostic dilemma posed by these cellular follicular cysts are discussed.

Granulomatous prostatitis: a spectrum including nonspecific, infectious, and spindle cell lesions.

Most granulomas of the prostate are nonspecific; infectious, post-operative, and allergic lesions are much less common. Fine-needle aspiration findings in the typical case are distinctive and easily recognized. Several series have been reported, but few have included histologic follow-up. We describe three cases of granulomatous prostatitis (GP) which showed a spectrum of findings confirmed by histologic sections. In all cases, carcinoma was suspected clinically. Case 1 represents typical nonspecific GP with epithelioid and multinucleated histiocytes. In case 2, aggregates of epithelioid histiocytes alternated with areas of necrosis and neutrophils. Histologically, the granulomas showed purulent centers. Silver stains revealed budding yeast in smears and sections. Cultures of FNA material subsequently revealed Cryptococcus. In case 3, the histiocytes were predominantly spindled and occurred singly and in groups. The differential diagnosis included reactive and neoplastic spindle cell lesions. Histologic sections showed GP with spindled histiocytes. Appreciation of the broad cytologic spectrum of GP will facilitate accurate cytologic diagnosis.

Oligoclonal T cell receptor gene rearrangements in blood lymphocytes of patients with acute Epstein-Barr virus-induced infectious mononucleosis.

Gene rearrangement studies were performed on blood lymphocytes from eight patients with acute Epstein-Barr virus-induced infectious mononucleosis. The diagnosis in each case was based on characteristic clinical, hematologic, and serologic findings. The blood lymphocytes in each patient consisted predominantly of CD8+ T cells. EBV DNA was detected in seven patients by Southern blot analysis (EBV Bam HI W probe, Bam HI). A germline configuration was found for the immunoglobulin heavy and light chain genes (JH probe, Bam HI and Eco RI; C kappa probe, Bam HI; and C lambda probe, Eco RI). T cell receptor gene rearrangements were detected with J gamma and J beta 1 + 2 probes. Using a J gamma probe with two different restriction enzymes (Bgl II and Eco RI), the blood from each patient showed several bands corresponding to the polyclonal pattern previously described in the blood of normal individuals. Using J beta 1 + 2 probes with two different restriction enzymes (Bgl II and Bam HI), each case showed from 3 to about 12 extragermline bands of varying intensity and in different locations from case to case. In addition, each case showed relative deletion of the J beta 1 germline band. This oligoclonal pattern of T cell receptor gene rearrangements has not been previously reported in benign or malignant T cell populations.

The spectrum of clinical and laboratory findings resulting from human herpesvirus-6 (HHV-6) in patients with mononucleosis-like illnesses not resulting from Epstein-Barr virus or cytomegalovirus.

Recently, the morphologic, immunologic, and molecular makeup of a new virus designated human herpesvirus-6 (HHV-6) has been described. Because cell cultures of HHV-6-infected mononuclear cells showed prominent lymphocytic changes, it could be anticipated that mononucleosis-like illnesses or lymphoproliferative disorders would turn out to be manifestations of active HHV-6 infection. In the present study, blood samples from 27 patients previously categorized as having non-Epstein-Barr virus (non-EBV)/noncytomegalovirus (non-CMV) heterophil-negative mononucleosis-like illnesses were tested for IgM and IgG antibodies to HHV-6. Eight of these patients (30%) had serologic evidence of active HHV-6 infection. The clinical spectrum includes a short-lived febrile illness, mild cervical lymphadenopathy, laboratory data suggestive of active viral hepatitis in two patients, and a prolonged febrile illness in a single patient with previously documented positive anti-HIV serology. The viral studies revealed the presence of fourfold HHV-6-specific IgG titer increases by immunofluorescent assay (IFA) in seven serially studied cases and positive IgM serology on one or more samples tested by IFA or enzyme-linked immunosorbent assay (ELISA) in all eight cases. The authors could not determine whether the illnesses represented primary HHV-6 infections in susceptible individuals or reactivation of latent virus. HHV-6 serologic studies may be indicated in patients with mononucleosis-like illnesses with atypical lymphocytosis when EBV and CMV test results are nondiagnostic.

Identical IgM antibodies recognizing a glycine-alanine epitope are induced during acute infection with Epstein-Barr virus and cytomegalovirus.

We studied antibody production in serial serum samples from patients with acute Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Sera were analyzed both by enzyme-linked immunosorbent assay (ELISA) using a synthetic peptide (P62) derived from the glycine-alanine repeating region of the Epstein-Barr nuclear antigen (EBNA-1) and by immunoblotting. In prior studies, we have shown that patients with acute EBV infection make IgM antibodies that react with this peptide, that recognize a viral-specific protein (EBNA-1), and that bind with a number of proteins present in uninfected cells; however, antibody binding to these autoantigens was inhibited by the peptide. IgG antibodies reactive with the peptide did not appear until months after the disease and were specific for the EBNA-1 protein. We now find that patients with acute CMV infection but not those with acute infections from a variety of other nonherpes organisms also produce IgM antibodies that recognize the EBV-derived peptide P62. These antibodies also appear to recognize the same cellular proteins as the EBV-induced IgM antibodies. The IgM antibodies appeared in all acutely infected CMV patients studied and occurred both in patients with previous EBV infections and in one patient studied who had not previously been exposed to EBV. It appears that infection with EBV or CMV can induce the synthesis of a very similar or identical set of IgM antibodies.

Fine-needle aspiration of lymph nodes in patients with acute infectious mononucleosis.

We studied lymph node fine-needle aspirations from 10 patients with primary Epstein-Barr virus (EBV) infections (infectious mononucleosis). There were five males and five females, aged 15-54 yr. The diagnoses were confirmed by blood morphology and heterophil antibody (HA) and EBV-specific serologic studies. Nine patients were HA-positive, nine were viral capsid antigen (VCA)-IgM-positive, and all 10 were VCA-IgG-positive and anti-EBV nuclear antigen (EBNA)-negative. Five patients were referred for fine-needle aspiration biopsies for clinically suspected malignant lymphoma (ML). Four of these patients had been tested for HA prior to fine-needle aspiration, with negative results in three cases. The heterophil-positive patient was referred for fine-needle aspiration due to very impressive unilateral cervical adenopathy. Cytologically, all cases showed atypia consisting of greater numbers of large immunoblastic lymphocytes than are usually seen in the reactive lymph node. Two cases were cytologically suspicious for malignant lymphoma but included a considerable background of polymorphic immunoblasts. We suggest that polymorphic immunoblastic proliferations in lymph node cytology are suggestive of infectious mononucleosis. Since several reactive and neoplastic processes mimic this pattern, cases not followed by both confirmatory serologic studies and resolution of adenopathy should be pursued by excisional lymph node biopsy.

Negative images of bacilli and mycobacterial infection: a study of fine-needle aspiration smears from lymph nodes in patients with AIDS.

In patients with the acquired immunodeficiency syndrome (AIDS), four cases of mycobacterial infection in which bacilli appeared as cylindrical, nonstaining "negative images" have been previously described. These may have been extracellular or within histiocyte cytoplasm, and they have been described in aspirations from liver, lymph node, and bone marrow and in bronchoalveolar lavage fluid. We report three additional examples of this finding in fine-needle aspirations from lymph nodes in AIDS patients infected with Mycobacterium avium-intracellulare. Our findings support the concept that these negative images of bacilli are diagnostic of mycobacterial infection. Air-dried Romanovsky-stained material is required for their identification.

Antibodies to an Epstein-Barr virus nuclear antigen synthetic peptide in infectious mononucleosis. Report of two cases.

The Epstein-Barr virus nuclear antigen (EBNA-1) contains a region of repeating glycine and alanine amino acids. It has been shown that this region contains a major epitope of EBNA-1. With well-characterized sequential sera from two cases of acute infectious mononucleosis, a specific IgM response was detected to the EBNA-1 synthetic peptide by enzyme-linked immunosorbent assay (ELISA). Conversely, an IgG response was observed in the convalescent phase of the illness with a progressive decline of the IgM antibodies. This response was observed with heterophil-positive and heterophil-negative EBV/IM. The peptide-specific serologic response was confirmed by immunoblotting, the serial serum samples on extracts of EBV transformed B-cells. There was excellent correlation between the antipeptide ELISA and blotting techniques.

Severe thrombocytopenia in Epstein-Barr virus-induced mononucleosis.

Severe thrombocytopenia is a rare complication of Epstein-Barr virus-induced infectious mononucleosis. We evaluated the clinical and laboratory data from seven patients seen between 1976 and 1985 whose lowest platelet counts varied from 3 to 25 x 10(9) per liter. Five of the seven patients were initially thought to have either acute leukemia or idiopathic thrombocytopenic purpura; eventually, however, primary Epstein-Barr virus infections were confirmed in all patients. Two of six patients tested had antiplatelet antibodies during the acute phase of their illnesses. Eight additional patients with acute disease who had only mild thrombocytopenia (94 to 144 x 10(9) per liter) were also tested for platelet antibodies with negative results. Steroid therapy was administered to three patients and platelet transfusions to one. All seven patients recovered with no serious hemorrhagic sequelae.

Heterophil-negative mononucleosis-like illnesses with atypical lymphocytosis in patients undergoing seroconversions to the human immunodeficiency virus.

The authors present data from four patients with acute heterophil-negative mononucleosis-like illnesses who were initially thought to have primary Epstein-Barr virus (EBV) infections but eventually were shown to be seroconverting to the human immunodeficiency virus (HIV). Widespread lymphadenopathy and blood smears indistinguishable from those typically encountered in the acute phase of infectious mononucleosis were present in all cases. There were also varying combinations of fever, sore throat, and malaise, as well as mild abnormalities of hepatic function and elevated cold agglutinins (anti-I). Anti-HIV was detected by both enzyme-linked immunosorbent assay and Western blot techniques in all cases, with increasing titers noted in two of three serially studied cases. In one patient, a dual infection with the hepatitis B virus was also documented. Diagnostic possibilities in patients with acute mononucleosis-like illnesses dominated by prominent lymphadenopathy should include primary seroconversions to HIV.

Transrectal fine needle biopsy of the prostate: combined histological and cytological technique.

Transrectal fine needle biopsy was performed on 50 patients with suspicious prostatic examinations using the Surecut and Chiba needles. The 21 gauge Surecut needle provided a core of tissue for routine histology in 42 of 50 patients (84 per cent) as well as cells for cytology in 46 of 50 (92 per cent). This was in contrast to positive cytology results with the 22 gauge Chiba needle in 44 of 50 patients (88 per cent). Fourteen cancers were detected: 12 by Surecut histology, 11 by Surecut cytology and 10 by Chiba cytology testing, for sensitivity rates of 86, 79 and 71 per cent, respectively. Our results indicate that the 21 gauge Surecut needle provides cytology results equivalent to the 22 gauge Chiba needle. However, the Surecut needle has the added advantage of providing a core of tissue for routine histological study, and it can be used safely as an outpatient procedure on unprepared bowel.

Primary spindle-cell sarcomas of the breast: diagnosis by fine-needle aspiration.

Primary breast sarcomas (excluding cytosarcoma phyllodes and its sarcomatous recurrences) are rare neoplasms. Few have been described in the aspiration cytology literature. We report the cytologic features of two cases of stromal sarcoma (both with the pattern of malignant fibrous histiocytoma) and two cases of angiosarcoma. The dominant cytologic features included individual atypical spindle cells and fragments of collagenous stroma. Tumor giant cells were present in one stromal sarcoma. Features of possible significance in the diagnosis of angiosarcoma include obvious vessel formation by atypical spindle cells, bridging of adjacent tumor fragments by spindle cells, and microacinar structures lined by atypical spindle cells. The differential diagnostic considerations in spindle-cell breast aspirations are discussed.

Basal-cell adenoma of the salivary gland: a benign adenoma that cytologically mimics adenoid cystic carcinoma.

We describe the fine-needle aspiration cytology of two cases of basal-cell adenoma (BCA) of the parotid gland. Both consisted of groups of small uniform cells with scant cytoplasm and occasional single cells. Small amounts of metachromatic stroma were present in smears from one case. The cytologic and histologic similarities between (BCA) and the solid type of adenoid cystic carcinoma are emphasized. Unequivocal distinction between these two entities may not be possible by cytologic criteria alone.