A 35-year experience with the post-sophomore fellowship in pathology: analysis of its effectiveness as a recruitment resource.

Recent reports have indicated a shortage of pathologists coming out of training programs over the next few years. This is due, in part, to a decrease in the number of medical students entering pathology and an overall decline in the popularity of the field as a specialty choice. Medical students electing to spend a year in a post-sophomore fellowship in pathology would be expected to enter the field at a higher than average rate. In this study, the specialty choices of 140 former student fellows were analyzed. The students included in the study were enrolled in a year-long University of California, Los Angeles post-sophomore fellowship in pathology between 1953 and 1988. Twenty-seven of the 140 students (19.3%) ultimately chose pathology as a career. This represents a 9- to 10-fold increase over the average percentage of medical students entering pathology through the match (less than 2%) for any given year. Of all students from the University of California, Los Angeles who entered pathology, 75% did not elect to spend a year in fellowship. Eighty percent of the former fellows chose some other field, medicine and surgery being the most popular choices.

Disseminated coccidioidomycosis detected by percutaneous liver biopsy in a liver transplant recipient.

The authors report the first case, to their knowledge, of disseminated coccidioidomycosis occurring in a liver transplant recipient. The case is also interesting in that the diagnosis of disseminated coccidioidomycosis was made fortuitously, only after finding the characteristic endosporulating spherules on a percutaneous liver biopsy. In addition, the authors reviewed the literature on post-transplant infection with particular emphasis on fungal pathogens. All studies concurred that Candida species was the most prevalent infecting fungal organism when both localized and disseminated forms of infection are included. Aspergillus was the second most common offender, and disseminated infection was associated with a very grave prognosis for the transplant recipient. Rare infections with Mucor and Cryptococcus neoformans are described in the literature.

Fine-needle aspiration of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors are a group of neoplasms encompassing leiomyoma, leiomyosarcoma, and an epithelioid variant of leiomyosarcoma, as well as lesions expressing neural differentiation. These neoplasms are rare and account for 1% of all gastrointestinal tumors. With increasing frequency, fine-needle aspiration (FNA) has been used to diagnose intra-abdominal neoplasms before institution of definitive treatment. We encountered four patients with gastrointestinal stromal tumors diagnosed by FNA who ultimately underwent surgical excision of their tumors. The age of the patients ranged from 57 to 88 years. Smears from the aspirates were cellular and consisted of numerous small spindle cells distributed as cohesive fragments and individual cells. The dispersed cell population appeared largely as stripped nuclei. Several nuclei had perinuclear or paranuclear vacuoles, similar to the "halos" seen in sections. Cytologic evidence of malignancy (pleomorphism, nuclear irregularity, mitoses) were not identified in smears. Corresponding histologic sections demonstrated varying degrees of malignancy ranging from benign or low grade to frankly sarcomatous gastrointestinal stromal tumors. We conclude that the diagnosis of gastrointestinal stromal tumors can be made with a certain degree of confidence by using FNA findings. However, predictions about potential aggressiveness are best reserved for gross and histologic examination of the resected specimen.

Prevalence of non-A,non-B hepatitis/hepatitis C virus antibody in human immunoglobulins.

Human intravenous immunoglobulins prepared by the cold ethanol fractionation technique of Cohn are considered safe with respect to infectivity. However, there have been several instances of transmission of both hepatitis B and non-A,non-B hepatitis viruses after administration of intravenous immunoglobulins. To determine the prevalence of hepatitis C virus antibody in intravenous immunoglobulins and protein preparations, 30 commercially available products were tested. Using the Abbott enzyme immunoassay for hepatitis C virus antibody, 27 of 30 (90%) immunoglobulins tested positive. The Ortho immunoassay showed that 28 of 30 (93%) were positive, with one discordant result between the Ortho and Abbott assays. An antigen-blocking or neutralization test (Abbott) confirmed the results of the Ortho assay. Bovine, sheep, goat, and horse sera also were tested before and after isolation of animal immunoglobulins. All results on the animal sera were negative, indicating that the fractionation process did not produce false-positive results. The high prevalence rate of hepatitis C virus antibody in intravenous immunoglobulins has important implications for follow-up of recipients, selection of serum donors, and implementation of anti-hepatitis C virus testing.

Prospective correlation of cervicovaginal cytologic and histologic specimens.

An effective, prospective, computer-guided method of correlation is reported. The mechanism for identification of cases, comparison of diagnoses, and reconciliation of discrepancies are explained. The results are similar to prior, retrospective, correlation studies. The benefits specific to this unique prospective approach include optimal capture of cases for correlation, minimization of errors before diagnoses are released to clinicians and patients, and internal standardization of diagnostic criteria. Three thousand four hundred and four consecutive paired cervicovaginal cytologies and biopsies were accessioned at the Pathology Department of Duke University Medical Center over a 43-month period. Of these, 481 paired cases (14%) had discordant diagnoses, defined as differing more than one degree of dysplasia or as dysplasia or carcinoma identified by only one modality. Additional evaluation reconciled the diagnostic differences in 35 cases. Eighteen initial diagnostic differences arose from cytologic screening errors, 16 from interpretive errors by staff pathologists, and one from superficial initial histologic sections. The remaining 446 discordances were attributed to sampling differences. The cytologic smear contained the diagnostic lesion in 40% of the cases and the biopsy the remainder, emphasizing the utility of pairing these sampling techniques in patients at risk for dysplasia.

Calcifying fibrous pseudotumor of pleura. A report of three cases of a newly described entity involving the pleura.

A newly recognized distinctive fibrous soft tissue lesion called "calcifying fibrous pseudotumor" (CFPT) was recently described in the soft tissues of the extremities, trunk, scrotum, groin, neck, or axilla. To date, CFPT has not been described in the pleura. The authors reviewed the clinical, radiologic, and pathologic features of three cases. A 23-year old woman and 34-year old man who presented with chest pain, and a 28-year old woman without chest symptoms were found to have a pleural mass on chest radiographs. Computed tomography (CT) scans of each patient revealed pleural-based nodular masses with central areas of increased attenuation due to calcifications. Each lesions consisted of circumscribed, but unencapsulated masses of hyalinized collagenous fibrotic tissue interspersed with lymphoplasmacytic infiltrates and calcifications, many of which had psammomatous features. The lesions were limited to the pleura and did not involve the underlying lung parenchyma. Electron microscopy in one case showed fibroblasts scattered in dense collagenous tissue. Calcifying fibrous pseudotumor is distinct from other pleural lesions such as fibrous tumor of pleura, calcified granulomas, calcified pleural plaques, and chronic fibrous pleuritis as well as intrapulmonary lesions such as hyalinizing granuloma, inflammatory pseudotumor, and amyloid. As in the soft tissues, local excision appears adequate therapy for CFPT of the pleura. If these lesions behave in a similar fashion to CFPT of soft tissues, one might expect a low frequency of local recurrence.

Do proficiency test results correlate with the work performance of screeners who screen Papanicolaou smears?

We rescreened Papanicolaou smear slides from 40,245 women, which had been examined by 81 cytology screeners, scored the screeners' work performance, and compared these scores with the results of the screeners' performance on glass slide and computer-based proficiency tests. All diagnoses (i.e., from the proficiency tests, the original slides, and the rescreened slides) were classified in the 4 diagnostic categories specified in the Clinical Laboratory Improvement Amendments. The rescreening scores were standardized to account for different distributions of abnormalities in the proficiency tests and rescreened slides. We compared a standardized score with the proficiency test scores. Of the cases, 91% were categorized as normal, benign, or reactive changes when rescreened, and 98% of these agreed with the original diagnosis. Sixteen percent of low-grade and 15% of high-grade intraepithelial lesions were classified as normal. The rank correlation between the rescreening scores and both proficiency tests was 0.24 using a scoring scheme for cytotechnologists. The correlation between the rescreening and proficiency testing scores indicates that performance on a 10-slide test gives some indication of the true performance of screeners. The computer-based test shows promise as an alternative to the glass slide test but needs further development and validation.

Glomus jugulare tumor metastatic to the sacrum after high-dose radiation therapy: case report.

A 47-year-old woman with left ear pain and hearing loss was diagnosed with a glomus jugulare tumor for which she received radiation therapy as the primary treatment. Over a period of 20 years, she developed temporal bone necrosis, brain stem calcifications, local tumor recurrence, and eventually metastases to her lungs and sacrum. This case underscores the often indolent nature of glomus jugulare tumors, the late sequelae of radiation therapy for benign intracranial tumors, and the potential of these tumors to metastasize. This patient's history suggests that aggressive surgical resection should be considered early for such tumors, particularly because radiation treatment does not ablate the tumor. This is only the second reported case of a glomus jugulare tumor metastatic to the sacrum.

Osteogenic sarcoma of the head and neck. The UCLA experience.

Eighteen cases of osteogenic sarcoma of the head and neck were treated at our institution between 1955 and 1987. The patients' ages ranged from 5 to 73 years, with a median age of 28 years. The sex distribution was equal. Follow-up ranged from 1 to 276 months, with a median of 79 months. The primary site of the tumor was the mandible in nine cases, maxilla and paranasal sinuses in six, skull in two, and orbit in one. Six of 18 patients were free of disease with greater than 5 years of follow-up. Four of the six received combined surgery, radiation therapy, and chemotherapy as their primary treatment. Of the five patients treated with surgery alone, four suffered recurrences, one of whom was salvaged with further surgery and chemotherapy. Five patients were treated initially without surgery. They received radiation therapy with or without chemotherapy; all five developed local recurrence. We conclude that osteogenic sarcoma of the head and neck is an aggressive tumor, prone to both local and distant failure. Based on our series and from published experience involving the extremities, osteogenic sarcoma of the head and neck should be managed with multimodality therapy.

Midline nasal destruction in cocaine abusers.

Idiopathic midline destructive disease (IMDD) is a diagnosis of exclusion in patients who manifest midline nasal necrosis with no specific etiology such as infection, tumor, or Wegener's granulomatosis. Recently, a group of cocaine abusers has been identified that manifests a syndrome that mimics IMDD, but is less fulminant in its course. To better define the natural history of this syndrome, we reviewed the medical records, radiographs, and pathologic material from five such patients treated at the University of California, Los Angeles. Other causes of midline nasal destruction were excluded in each patient on the basis of histopathology, cultures, and laboratory tests. Biopsy material, available in four patients, demonstrated inflammation and necrosis without vasculitis. Treatment was conservative in four of the five patients, using antibiotics, local care, debridement, and cessation of cocaine use. During the follow-up period, progressive disease developed in one of the five patients, requiring radiation and steroid therapy. We conclude that the treatment of midline nasal destruction in cocaine abusers should initially be conservative, once other etiologies have been systematically excluded.

Fine-needle aspiration cytology of adenoid (acantholytic) squamous-cell carcinoma.

Adenoid squamous-cell carcinoma (ASCCa) is an uncommon cancer which occurs most frequently in the skin of the head and neck region of elderly, sun-exposed individuals. Histologically, ASCCa is characterized by gland-like, "adenoid" cell groups with a central, detached acantholytic cellular component and an intact peripheral rim of cells. The cytological features of five fine-needle aspiration cytology (FNAC) samples from four patients with primary or metastatic ASCCa are presented. These were assessed for features which would allow distinction of this variant from conventional squamous carcinoma. The adenoid component was represented in FNAC by intact, sometimes three-dimensional cell groups simulating glandular structures. Also present were cells in short chains of two or three in single cell files and scattered, individual dyskeratotic cells. Individual cells had rounded, accentuated borders, cytoplasmic keratinization, and often pyknotic nuclei, representing acantholytic cells from the adenoid "lumens." Features of malignancy, including cellular atypia and increased mitotic rate, were present allowing for distinction between ASCCa and benign acantholytic processes such as pemphigus.

Cytologically low grade malignancies: an important interpretative pitfall responsible for false negative diagnoses in fine-needle aspiration of the breast.

Failure to diagnose breast carcinoma by fine-needle aspiration (FNA) is a major obstacle to expanded use of that technique. While the majority of false negative diagnoses are due to inadequate sampling and insufficient specimens, a significant minority of false negative cases result from inaccurate interpretation of adequate material. Low grade carcinomas including lobular, tubular, low grade adenosquamous, and papillary carcinomas appear to account for many of these diagnostic errors. Careful attention to nuclear detail, monomorphism of cell population and the presence of neoplastic cells with retained cytoplasm should allow the recognition of the majority of these neoplasms as malignant by cytologic examination.

Fine-needle aspiration of a primary right atrial myxoma.

Cardiac myxomas are rare neoplasms usually diagnosed by echocardiography. Preoperative tissue diagnosis is usually not obtained because of the location of these neoplasms. Their cytologic appearance has only been reported from touch imprints of operative specimens or aspirates of metastatic deposits. We report the cytologic appearance of a right atrial myxoma characterized by bland spindle cells and fragments of myxoid debris.

Fine-needle aspiration of inflammatory carcinoma of the breast.

Inflammatory carcinoma of the breast is an uncommon clinicopathologic entity which is characterized by a distinctive clinical appearance and poor prognosis. Histopathologically, it is characterized by plugging of dermal lymphatics with tumor emboli. Because this lesion usually does not form a discrete palpable mass, it is not as amenable to diagnosis by fine-needle aspiration (FNA) as other breast lesions. In the following, we report our experience with establishing the diagnosis of inflammatory carcinoma by FNA. Three patients underwent FNA for confirmation of clinically suspected inflammatory carcinoma. All aspirations were performed by a cytopathologist and required multiple passes to obtain diagnostic material. Aspirates were paucicellular and contained fragments of fibrous or adipose tissue. Malignant cells were predominantly distributed in tight, three-dimensional clusters and were identifiable as tumor cells based on large size, nuclear irregularity, and increased nuclear to cytoplasmic ratio. Unlike aspirates from conventional breast carcinoma, individual dispersed cells and cellular discohesiveness were not prominent features. Subsequent histologic material from these patients revealed the characteristic tumor emboli plugging dermal lymphatics. We conclude that in the appropriate setting, the diagnosis of inflammatory carcinoma can be established by FNA.

Fine-needle aspiration cytology of ganglion cysts.

Ganglion cyst is a relatively common lesion resulting from mucoid, cystic degeneration of soft tissues adjacent to a joint space. Aspiration of cyst contents has been increasingly advocated as a diagnostic and, in some instances, therapeutic modality. We report the fine-needle aspiration cytologic (FNAC) findings from seven cases of ganglion cyst. These include the aspiration of thick, gelatinous fluid and a smear comprised of rare histiocytes embedded in a mucoid matrix. Although these findings are nonspecific, we believe that in the appropriate clinical setting, the diagnosis of ganglion cyst can be made with confidence by FNA.

Fine-needle aspiration cytology of pseudosarcomatous lesions of soft tissue.

Pseudosarcomatous lesions are benign neoplasms of the musculoskeletal system that are likely to be misdiagnosed as malignant, based on clinical and histologic features. These include soft-tissue "tumors" considered reactive or reparative lesions such as nodular fasciitis and myositis ossificans. Also included in the "pseudosarcoma" category are benign neoplasms which show "pseudoanaplastic" cytologic atypia. The latter include lipoma, leiomyoma, angiomyolipoma, and benign peripheral nerve-sheath tumors. These neoplasms, particularly the reparative processes and the nerve sheath tumors, are increasingly being subjected to initial diagnosis by fine-needle aspiration cytology. Even by conventional cytology this group of lesions represents a well-known pitfall for the diagnostic pathologist. We review some cytologic features: repair-like change, cohesion of cellular fragments, and presence of "normal" elements in the aspirate, which may help the cytopathologist avoid misdiagnosis of these notoriously difficult entities.

Fine-needle aspiration cytology findings in a case of aggressive angiomyxoma: a case report and review of the literature.

Aggressive angiomyxomas are uncommon but distinct soft-tissue neoplasms occurring predominantly in the pelvis and peritoneum of females, but they have occasionally been reported in association with inguinal hernias in males. Histologically, these neoplasms are characterized by a proliferation of spindle- or stellate-shaped cells widely separated by loose myxoid stroma in which is dispersed a prominent vascular component. The vascular component is comprised of large, thick-walled vessels that generally to not show an arborizing pattern. Mitotic activity has been exceedingly low in the cases reported. Because of their occurrence within the groin, these lesions may undergo fine-needle aspiration (FNA). Cytologic examination of this material will reveal hypocellular smears containing scattered spindle cells with bipolar cytoplasmic processes, as well as bland stellate cells. The nuclei are fusiform to oval with a bland chromatin pattern. The stromal cells lie in a background of watery myxoid material. While specific diagnosis by FNA is not possible, the recognition of this cytologic appearance should exclude lymphoproliferative processes as well as metastatic disease from the differential diagnosis. Careful attention to cytologic detail should also help exclude certain other myxoid neoplasms, especially myxoid liposarcoma. Once the myxoid stromal nature of the proliferation is recognized, a differential diagnosis of myxoid lesions can be considered along with a recommendation for open biopsy to establish the definitive diagnosis.

Fine-needle aspiration of epithelioid malignant peripheral nerve sheath tumor (epithelioid malignant schwannoma).

The epithelioid variant of malignant peripheral nerve sheath tumor (MPNST), also known as malignant epithelioid schwannoma, is a relatively rare and recently characterized clinicopathologic entity. The epithelioid variant of MPNST shares many clinical features with conventional MPNST but is characterized by different histologic and cytologic features. These include a distinctive nesting pattern and an abundance of cytoplasm not seen in histology of conventional nerve sheath tumors. Cytologically, the epitheliod variant shows a propensity to cellular discohesiveness and a plasmacytoid or epitheliod appearance that is in contradistinction to the spindled appearance of the usual MPNST. Herein, we report our experience with fine-needle aspiration (FNA) of two epithelioid malignant schwannomas and discuss the FNA cytologic differential diagnosis.

Utility of fine-needle aspiration in the diagnosis of recurrent pulmonary lymphangioleiomyomatosis: a case report.

Pulmonary lymphangioleiomyomatosis (PLAM) is a rare disease of undetermined cause that almost exclusively occurs in women of child-bearing age and is characterized by distinct clinical, radiologic, and pathologic findings. PLAM is usually fatal unless treated with hormonal manipulation or lung transplantation. Primary diagnosis usually requires open lung biopsy to demonstrate the characteristic hamartomatous smooth muscle proliferation. To date, cytologic diagnosis of LAM has been limited to an ancillary role. Herein, we report the diagnosis of this neoplasm in a recurrence in an abdominal lymph node using fine-needle aspiration.