Kenneth O. Devaney

Hepatobiliary cystadenoma and cystadenocarcinoma. A light microscopic and immunohistochemical study of 70 patients

Fifty-two hepatobiliary cystadenomas and 18 hepatobiliary cystadenocarcinomas were drawn from the files of the Armed Forces Institute of Pathology and Rhode Island Hospital and studied in an attempt to correlate light microscopic features of the tumors with immunohistochemical and follow-up data. The cystadenoma patients ranged in age from 2 to 87 years at the time of initial diagnosis (mean, 45 years). All the cystadenomas were multilocular with benign cuboidal to columnar epithelium, and 44 (85%) had densely cellular spindle cell (“ovarian-like”) stromata; 96% were female. Fifty-one cystadenomas were macrocystic lesions, typically lined by mucinous epithelium; one of the benign lesions was a serous cystadenoma (microcystic adenoma) reminiscent of the more commonly encountered pancreatic lesion of the same name. The cystadenocarcinoma patients ranged in age from 24 to 90 years at the time of first diagnosis (mean, 59 years); eight patients (44%) were male. All but one of the lesions were multilocular with malignant in situ (one case) or invasive tubulopapillary (15 cases), solid (one case), or adenosquamous (one case) epithelial components. Areas of preexisting benign cystadenoma were found in six (33%), an observation suggesting that benign lesions may evolve into malignant ones in some patients. Most cystadenomas and cystadenomas and cystadenocarcinomas arose in the liver, a few in the extrahepatic biliary system (including the gallbladder). On follow-up, the cystadenoma patients in general were successfully treated by surgical excision of the lesions in toto; patients treated by subtotal resection often had persistent symptomatic disease. Four cystadenocarcinoma patients died of their tumors; another two patients were alive with persistent disease at last follow-up. In both the benign and the malignant lesions, most tumor cells were positive on immunohistochemical staining with antibodies to cytokeratin. epithelial membrane antigen, and carcinoembryonic antigen; scattered chromogranin-positive cells also appeared in a few tumors of both types. Immunohistochemistry did not yield a diagnostic immunoprofile to distinguish cystadenoma from cystadenocarcinoma or from other epithelial lesions arising within the abdominal cavity. At least two types of cystadenocarcinoma exist, one developing exclusively in female patients, usually accompanied by an “ovarian-like” stroma, which follows an indolent course:and the other, lacking the distinctive cellular stroma, seen in males, follows a more aggress ve course and is more likely to result in the patients death from tumor. It remains an open question whether the cystadenocarcinomas lacking a mesenchymal stroma, which arise in women, will follow the same aggressive course as similar lesions arising in men.

Hepatic sarcoidosis. Clinicopathologic features in 100 patients.

The patterns of hepatic injury were studied in 100 patients with a diagnosis of sarcoidosis and clinical evidence of liver disease that led to diagnostic liver biopsy. Granulomas were present in all patients; they occupied from <1% to >90% of the total volume of tissue examined and were most often located in the portal/periportal region. In none of the 100 cases were infectious organisms identified by special stains, culture, or serology. In 99% of cases, these granulomas were noncaseating; in one of the 100 cases central caseation was noted. In addition to the granulomas present in all biopsies, three broad categories of histologic change were found: cholestatic (58%), necroinflammatory (41%), and vascular (20%). Among those with cholestasis, 19 patients had bile duct lesions similar to primary biliary cirrhosis, whereas another 13 had a pattern of periductal fibrosis reminiscent of primary sclerosing cholangitis. In 37 patients with chronic cholestasis, a decrease in the number of bile ducts (ductopenia) was noted. Twelve patients had an acute cholangitis suggestive of mechanical obstruction—although no clinical evidence of ductal obstruction was found. Necroinflammatory changes included spotty necrosis suggesting hepatitis of diverse etiologies (including viral infection and drug reaction) and chronic portal inflammation suggestive of chronic active hepatitis. Vascular changes consisted of sinusoidal dilatation (14 cases) and nodular regenerative hyperplasia (9 cases). In 6% of the patients, the only changes in the biopsy were those of granulomatous inflammation; each of these patients had a dominant mass (“sarcoidoma”), which had been biopsied to rule out tumor. Fibrosis was seen in 21% of the biopsies—periportal (13%), bridging (2%), or cirrhosis (6%). It is clear that sarcoidosis can cause progressive liver disease with a wide array of histologic features that can mimic those of other primary liver diseases

Lymphoid Pneumonitis in 50 Adult Patients Infected with the Human Immunodeficiency Virus : Lymphocytic Interstitial Pneumonitis versus Nonspecific Interstitial Pneumonitis

Lymphocytic interstitial pneumonitis (LIP) and nonspecific interstitial pneumonitis (NIP) are pulmonary complications of human immunodeficiency virus (HIV) infection that occur in the absence of a detectable opportunistic infection or neoplasm. We reviewed lung biopsy specimens from 50 adult HIV-infected patients, of whom four had LIP and 46 had NIP. The majority (47 of 50) of specimens from patients with NIP showed mild chronic interstitial pneumonitis (CIP/NIP), with three showing features of diffuse alveolar damage, organizing phase. In contrast to CIP/NIP, the five specimens from four patients with LIP demonstrated more extensive lymphocytic interstitial infiltrates that extended into the alveolar septal interstitium. The majority of the interstitial lymphocytes in both NIP and LIP were of T-cell origin and stained for UCHL-1. The etiologies of NIP and LIP remain unknown. Since the common opportunistic infections were excluded by routine methods, we sought, with special techniques, to investigate whether HIV, Epstein-Barr virus (EBV), or cytomegalovirus (CMV) could be identified in lung biopsy specimens from these patients. By in situ hybridization, we found one LIP specimen with expression of large amounts of HIV RNA primarily within macrophages in germinal centers; in the remaining specimens, occasional cells expressing HIV RNA were found (two LIP and four NIP). Neither CMV nor EBV was found by in situ hybridization in seven specimens; in these same specimens EBV was detected using the polymerase chain reaction in only one case of NIP, similar to results in control specimens. These results, together with the knowledge that lymphocytic pulmonary lesions may be caused by lentiviruses in humans and animals, suggest that HIV plays a significant role in the pathogenesis of both NIP and LIP in adult HIV-infected patients; in contrast, our data do not demonstrate a direct role for either EBV or CMV.

Synovial hemangioma: A report of 20 cases with differential diagnostic considerations

True synovial-based hemangiomas are uncommon lesions and, as such, may enter the differential diagnosis of other lesions encountered more frequently in clinical practice, including pigmented villonodular synovitis and traumatic hemarthrosis. The consultation files of the Armed Forces Institute of Pathology were searched for benign vascular lesions diagnosed as synovial or bursal hemangiomas vascular lesions diagnosed as synovial or bursal hemangiomas submitted between the years 1960 and 1985; 20 cases of synovial hemangioma were identified. The patients ranged in age from 9 to 49 years at the time of presentation (average age, 25 years). Sixty-five percent of the patients were male; 35% were female. Presenting symptoms included pain and swelling (31%), pain alone (31%), and a painless mass (31%). Affected regions included the knee (60%), the elbow (30%), and the finger (10%). In 65% of cases the lesion was confined to the intra-articular synovium; in 30% of cases the hemangioma was located in a bursa adjacent to a joint. One case was located largely within the joint cavity but had an area of extension into the suprapatellar recess. The dominant histologic patterns included cavernous hemangioma (50%), lobular capillary hemangioma (25%), arteriovenous hemangioma (20%), and venous hemangioma (5%). One lesion (which had been incompletely excised) was removed in its entirety 3 months after the initial subtotal resection; otherwise, none of the patients studied developed recurrent disease. The clinical diagnosis of hemangioma was made in 22% of cases, while an initial pathologic diagnosis of hemangioma was reached in 67% of cases. Pathologic differential diagnostic considerations include nonspecific synovitis/bursitis, pigmented villonodular synovitis, nodular synovitis, and organizing hemorrhage. A relationship between synovial hemangioma and pigmented villonodular synovitis was not suggested by this analysis of our material.

Cortical osteofibrous dysplasia of long bone and its relationship to adamantinoma. A clinicopathologic study of 30 cases.

Thirty cases of cortical osteofibrous dysplasia (COFD) were studied in an attempt at defining the relationship of COFD to adamantinoma. The patients ranged in age from newborn to 39 years (mean 13.4 years). The male:female ratio was 1:1. Presenting symptoms were most often pain or a mass. The tibia was involved in all 30 patients; in addition, the ipsilateral fibula was involved in five patients (17%). The histologic appearance of the lesions was dominated by the combination of woven bone trabeculae with prominent osteoblastic rimming and a loose, slightly myxoid stroma (less heavily collagenized in most instances than usually encountered in intramedullary fibrous dysplasia). Results of immunohistochemical study showed isolated cytokeratin-positive cells in the stroma of 28 of the lesions (93%). However, hyperchromatic epithelial islands characteristic of adamantinoma were not found in any of the 30 cases. A control population of 50 fibro-osseous lesions (intramedullary fibrous dysplasia, sclerosing fibroxanthoma, and cranial ossifying fibroma) was studied immunohistochemically; in none of these control cases were cytokeratin-positive cells found. Follow-up data were obtained in 17 cases (57%); the period ranged from 1 to 16 years (mean 6.05 years). Certain overlapping clinical features (including the location of the vast majority of the lesions in the tibia and, less often, the fibula) and the morphologic similarities of many areas of COFD and adamantinoma (particularly the shared presence of cytokeratin-positive cells) suggest a more than coincidental association between COFD and adamantinoma. However, to date none of the 30 cases of COFD evaluated in this study has developed an adamantinoma.

Sinonasal Malignant Lymphomas: A Distinct Clinicopathological Category

Sinonasal lymphomas represent a distinct subset of extranodal head and neck lymphomas. While sinonasal lymphomas are relatively rare in Western countries, in Asian populations they are the second most frequent group of extranodal lymphomas, after gastrointestinal lymphomas. With advances in immunohistochemistry, these lymphomas have been separated into B-cell, T-cell, and most recently into natural killer (NK) cell phenotypes. The B-cell phenotype is typically located in the paranasal sinuses and has a slight predominance in Western countries. The T/NK-cell phenotype is the most common in Asian and South American countries. These tumors are typically located in the nasal cavity and have an aggressive, angioinvasive growth pattern that often results in necrosis and bony erosion. Thus, sinonasal lymphomas have been included in the past with other destructive malignant and benign lesions under the descriptive and nonspecific name lethal midline granuloma. Patients are classically in the sixth to eighth decades, with a 2:1 male-to-female ratio. The prognosis is generally better than that of nodal-based lymphomas of similar histologic grade. Treatment is a combination of local irradiation and chemotherapy with an anthracycline-based regimen.

Sentinel lymph node biopsy in head and neck cancer

In the past decade, the technique of sentinel lymph node biopsy (SLNB) has been applied to a vast array of primary neoplasms, ranging from head and neck melanoma to vulvar carcinoma. At present, experience with SLNB is greatest in patients with melanoma and breast cancer. In view of the well known complications associated with cervical node dissection, it has been suspected for some time that cervical SLNB, if successful, might reduce the morbidity associated with the definitive care of patients with head and neck cancers. This report assesses the current status of SLNB in the treatment of head and neck cancers; while formal investigations of the efficacy of this technique are recommended, SLNB has not yet been demonstrated to possess the same level of utility seen in SLNB in melanoma and breast cancer patients. As a consequence, the application of SLNB to head and neck cancers remains an experimental technique--one which has not yet acquired the status of the standard of patient care.

Lipomatous hemangiopericytoma: a rare variant of hemangiopericytoma that may be confused with liposarcoma.

We describe the clinicopathologic features and biologic behavior of 16 cases of histologically benign hemangiopericytoma containing a variable amount of mature fat as an intrinsic part of the neoplasm. These so-called lipomatous hemangiopericytomas occurred primarily in men (12 men and 4 women) with a mean age of 54 years (range, 33-74 years). All occurred in deep soft tissue and had an average size of 10 cm when first detected. All were characterized by a relatively sharp border and typical histologic features of hemangiopericytomas, including oval to round cells surrounding a sinusoidal and staghorn vasculature often with perivascular hyalinization. Mature fat varied in amount but usually occupied approximately one quarter to three quarters of the area of tumor. Mitotic activity was low, with more than half the cases having no mitotic activity. Five cases showed moderate nuclear atypia. In four cases, the pericytic regions had sclerotic zones. In contrast to liposarcoma, neither lipoblasts nor isolated atypical hyperchromatic cells within mature fat, as are seen in well-differentiated liposarcoma, were present. Immunohistochemistry performed in four cases showed factor XIIIa in tumor cells and an intricate pattern of immunoreactivity around cells for type IV collagen. CD34 and smooth-muscle actins were identified in two of four cases. Follow-up in seven cases showed no recurrences or metastases within the follow-up period of 1 to 7 years. Because these lesions are located in deep soft tissue and contain large amounts of mature fat, they could be mistaken for well-differentiated liposarcomas in limited biopsy material, although the distinction is easily made in examining the entire specimen. The lipomatous hemangiopericytoma represents yet another example of a bimodal mesenchymal tumor containing mature fat and raises the question of whether a common cytogenetic abnormality can explain the emergence of two clonal populations in this hybrid tumor.

Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Head and Neck Cancers: Review of the Literature

In a minority of patients with malignant tumors, signs and symptoms develop that cannot be explained on the basis of the mass effect produced by the primary tumor or its metastases, or production of a hormone normally associated with the tissue type that has given rise to the malignant tumor; these peculiar symptom complexes are known as paraneoplastic syndromes, and may be divided into endocrinologic, dermatologic, hematologic, neurologic, and osteoarticular manifestations. In the head and neck region in particular, the syndrome of inappropriate antidiuretic hormone production (SIADH, or Schwartz-Bartter syndrome) is a well-recognized form of paraneoplastic syndrome that may accompany head and neck malignancies. Most of such tumors are squamous carcinomas, with lesser numbers of olfactory neuroblastomas, small cell neuroendocrine carcinomas, adenoid cystic carcinomas, and undifferentiated carcinomas; sarcoma was reported in only a single instance. The lesions associated with the development of SIADH have most often been located in the oral cavity, and less often in the larynx, nasopharynx, hypopharynx, nasal cavity, maxillary sinus, parapharyngeal space, salivary glands, and oropharynx. Key features of SIADH include serum hypo-osmolality; an unexpectedly high urinary specific gravity; an absence of edema or dehydration; normal adrenal, thyroid, and renal function; hyponatremia; and an elevation of plasma vasopressin.

Wegener's Granulomatosis of the Head and Neck

Among the more puzzling non-neoplastic necrotizing lesions of the head and neck area is Wegeners granulomatosis. This is a condition of unknown cause that may present (in the head and neck area) with ulceration of the nasal septum, sinus mucosa, oral mucosa, or external ear canal, or even destruction of the vocal cord. Diagnosis depends on the pathologic finding of a characteristic inflammatory reaction pattern (which, in its best-developed form, includes necrosis, granulomatous inflammation, and vasculitis) and the serum finding of an elevated antinuclear cytoplasmic antigen. Treatment is principally medical, with the use of powerful immunosuppressive agents. Distinction from other conditions that may mimic Wegeners granulomatosis (such as malignant lymphoma and infections) is of critical importance in constructing an appropriate treatment strategy.