Meningioma of the paranasal sinuses. A report of two cases.

Two patients presented with primary meningiomas arising in the paranasal sinuses. Despite nonspecific symptoms, both patients had extensive local clinical disease. One patient had a lateral rhinotomy with total removal of tumor; he has remained well for 3 years. The second patient, who was not a surgical candidate because of her cerebrovascular disease, was identified retrospectively. Her tumor was not originally studied using current day morphologic methods. She was irradiated following a diagnosis of malignant tumor. The histologic features of nasal meningioma are similar to those of conventional intracranial lesions, including nuclear pseudoinclusions. Although the unusual location may suggest carcinoma, melanoma, or olfactory neuroblastoma, adjunctive use of electron microscopy and immunohistochemistry can be combined to arrive at the correct diagnosis.

Pregnancy-associated ectopic decidua.

Extrauterine formation of decidua of stromal cells has been well described, particularly in the cervix and ovary. Sporadic reports have documented decidua formation of peritoneal surfaces and lymph nodes as well as ovarian ectopic decidua in pregnant patients. The apparent hormonal mechanism of this phenomenon suggests a relationship to endometriosis. Between 1983 and 1986, tissue from 10 pregnant patients (acquired from nine at cesarean section and from one at appendectomy) demonstrated submesothelial decidua formation in the form of microscopic nodules and diffuse cell arrangements in an edematous stroma. Some cases showed mild chronic inflammation. An intracytoplasmic lipofusin-type pigment was observed in one case. Four cases had diffuse omental involvement: two with small amounts of free peritoneal blood and two with peritoneal adhesions. Three cases were associated with paratubal cysts: two of these occurred in the uterine and appendiceal serosa, respectively, and one case showed involvement of a retroperitoneal lymph node associated with a pheochromocytoma. No specific gross observations were noted at surgery. There was no prior or subsequent evidence of endometriosis. A review of 958 elective tubal ligations performed between 1983 and 1985 demonstrated 52 examples (5.5%) of serosal decidua formation. Ectopic stromal decidua formation in pregnancy is: (a) a physiologic phenomenon related to the possible specialized sensitivity of the superficial coelomic stroma to progesterone; and (b) diffusely distributed in the peritoneum although it is a clinicopathologic process distinct from endometriosis.

Vasectomy: subclinical pathologic changes.

The nature of the local histopathologic changes secondary to vasectomy is described in tissue excised at vasovasostomy in 37 secondarily infertile patients. Segments of surgically removed vasa were also studied in four patients with primary infertility who underwent scrotal explorations and subsequent vasoepididymostomy. Except for infertility, all patients were asymptomatic. Three, often concurrent, inflammatory or proliferative changes were found in 50 of 76 segments of vasa deferentia. These included suture granuloma, sperm granuloma, and vasitis nodosa, the last being a ductular proliferation originating from the central vas lumen and extending into the perivasal soft tissues. Vasitis nodosa occurred in 66% of the patients, and although it was often found with a sperm granuloma, it did occur by itself and is a lesion which should be recognized.

Sinonasal undifferentiated carcinoma. An aggressive neoplasm derived from schneiderian epithelium and distinct from olfactory neuroblastoma.

Eight cases of a highly aggressive undifferentiated carcinoma of the nasal cavity and paranasal sinuses are described. The patients, who ranged in age from 30-77 years, had multiple sinonasal symptoms, and each had involvement of the nasal cavity, maxillary antrum, and ethmoid sinus. Six tumors extended into the orbital bones, and five penetrated the cranial cavity. Five patients died of disease from 1 to 41 months after diagnosis (median: 4 months), and three are alive with tumor less than 1 year following diagnosis. Microscopically, the neoplasms formed nests, trabeculae, and sheets containing medium-sized cells with small to moderate amounts of eosinophilic cytoplasm. A high mitotic rate, tumor necrosis, and prominent vascular permeation were characteristic. Seven neoplasms were immunoreactive for cytokeratin, five for epithelial membrane antigen, and four for neuron-specific enolase. Ultrastructurally, occasional small desmosomes and rare membrane-bound, dense-core granules were observed. Sinonasal undifferentiated carcinoma is a distinctive clinicopathologic entity that must be distinguished from other, less aggressive sinonasal neoplasms.

The spectrum of olfactory neural tumors. A light-microscopic immunohistochemical and ultrastructural analysis.

Twenty-eight malignant olfactory neural tumors representative of the histologic spectrum commonly designated as olfactory neuroblastoma were subdivided into two groups: Group I closely resembling classical neuroblastoma (20 cases), and Group II exhibiting neuroendocrine features (eight cases). Immunohistochemically, the tumors were analyzed by using antibodies to keratin, neurofilament protein, S-100, and neuron specific enolase. Neuron specific enolase was the most consistently positive in both groups. Single S-100 positive cells, within or at the edges of tumor nests, often corresponded ultrastructurally to Schwann cells at the tumor-stroma interface. Keratin and neurofilament proteins were expressed singly or together by a small number of cases in both groups. All 11 tumors examined ultrastructurally exhibited neuronal processes containing dense-core granules. The results indicate the following: (a) the reliable diagnostic utility of electron microscopy; (b) the frequent occurrence of Schwann cells in these tumors despite their inconspicuousness by light microscopy; and (c) the unexpected expression of keratin by tumors in both groups. The single or coexpression of keratin-neurofilament protein may define a subset of these tumors for which the clinical significance is presently unclear.

Peliosis: a morphologic curiosity becomes an iatrogenic problem.

Peliosis is a morphologic entity describing a condition of blood filled spaces, most frequently occurring in the liver. In recent years it has evolved from an anatomic curiosity seen at autopsy to a potential clinical problem in view of its association with the administration of anabolic steroid hormones. The pathogenesis and predilection of peliosis for the liver remain unexplained. This article reports five patients with peliosis, four with splenic involvement, all but one of whom received an anabolic steroid preparation. One patient died as a result of rupture of the splenic peliotic spaces. The diagnosis in three cases was established on the basis of surgical material, i.e., liver biopsy or splenectomy. An increased awareness of peliosis in patients at risk, as well as an appreciation for the histopathologic changes in less advanced cases, may become an important issue for the surgical pathologist.

Early morphologic diagnosis of herpes simplex virus encephalitis: advantages of electron microscopy and immunoperoxidase staining.

The authors compared three morphologic techniques that can be used in the diagnosis of herpes simplex virus encephalitis. The pathologic material was derived from brain biopsy, autopsy, or both in ten culture-proven cases. On conventional light microscopic examination, typical intranuclear Cowdry type A inclusions were recorded as absent (one case), rare (six cases), or numerous (three cases). Electron microscopic evaluation, performed in nine cases, revealed intranuclear viral particles in five biopsy and two autopsy cases, including four cases in which inclusions were rare or absent on light microscopy. In one biopsy specimen, unequivocal virus particles could not be identified ultrastructurally, although they were present in subsequent autopsy material. Immunoperoxidase staining using the peroxidase-antiperoxidase (PAP) method and type-specific anti-herpes simplex type 1 antiserum, performed on paraffin-embedded tissue, demonstrated strongly positive specific immunoreactivity in all ten cases. The potential for rapid specimen preparation, the relative sensitivity of electron microscopy, and the extreme sensitivity and specificity of the PAP-immunoperoxidase method offer obvious advantages in the early morphologic diagnosis of herpes simplex virus encephalitis.

"Carcinoid" tumor of the breast. A variant of conventional breast cancer?

A breast tumor with the morphologic features of a carcinoid tumor and containing large amounts of estrogen receptor protein was associated with areas of typical in situ and infiltrating lobular carcinoma. The carcinoid areas were argyrophilic and ultrastructurally contained electron dense granules on which silver grains were localized. Of 21 other examples of ordinary breast cancer, five showed histologic similarities to carcinoid tumors. Focal argyrophilia was observed in 11 invasive tumors. The presence of argyrophilic granules could not be correlated with the presence of "neurosecretory" granules, although groups of such granules were found in one case of in situ lobular carcinoma. Argyrophilic and "neurosecretory" granules imply the presence of hormonal substances, although in breast tumors these granules have not yet been chemically or immunochemically characterized. Until such evidence becomes available it would appear that most cases reported as primary carcinoid tumors of the breast have much more in common with conventional breast cancer than with the usual carcinoid tumor. Within this context it can be acknowledged that some breast cancers may focally exhibit a carcinoid-like differentiation.

Spindle cell carcinoma of the conjunctiva.

Spindle cell carcinoma, a variant of squamous cell carcinoma, has long been recognized in numerous tissues (including the skin, the upper respiratory tract, the oral cavity, and the esophagus). Two cases of spindle cell carcinoma of the conjunctiva are reported here. Histopathologic examination of these cases shows the characteristic spindle-shaped cells in continuity with the overlying epithelium. Electron microscopy of one case showed desmosomes and cytoplasmic tonofibril-like material. Our direct experience with one of these two cases has shown the malignant neoplasm to be aggressive.

Necrotizing squamous/mucinous metaplasia in oncocytic salivary gland tumors. A potential diagnostic problem.

Tumor necrosis and squamous and/or mucinous metaplasia was found in 4 of 26 oncocytic salivary gland tumors (24 Warthin's tumors and 2 oncocytomas). The necrosis was extensive in two cases, producing architectural and cytologic atypia sufficient to simulate a squamous carcinoma. In a third tumor, necrotic and inflammatory debris occurred within dilated tumor spaces exhibiting squamous and mucinous foci, suggesting low-grade mucoepidermoid carcinoma. Adequate sampling revealed Warthin's tumors in all four cases. An additional 13 tumors showed incidental foci of squamous metaplasia, often accompanied by stromal scarring but without necrosis. Four of these tumors also had focal mucinous metaplasia. In the adjacent non-neoplastic salivary gland, oncocytic metaplasia of ducts was seen in 22 glands; there were 7 oncocytic cysts and 3 oncocytic nodules. The tumor necrosis and metaplasia are reminiscent of necrotizing sialometaplasia of the minor salivary gland, thought to be ischemic in origin. The etiology of necrotizing squamous/mucinous metaplasia described here and the extent to which oncocytosis contributes to these changes is unknown. Possibly the extravasation of oncocytic and/or mucinous secretions or cyst contents may result in the reactive changes observed. Necrotizing sialometaplasia and squamous/mucinous metaplasia of oncocytic tumors appear to be related only morphologically, but the shared histologic features may be useful in excluding the diagnosis of salivary gland carcinoma.

Squamous carcinoma of the nasal vestibule: an analysis of five cases and literature review.

Five examples of squamous carcinoma of the nasal vestibule are reported. Possibly because this keratinizing tumor is histopathologically identical to squamous cancer in other locations, reports of this tumor in the pathology literature are uncommon. The patients were four men and one woman, of whom three men were smokers, although there are no consistent published associations with any environmental toxins to determine patients at risk. All five patients had localized disease treated by combinations of surgery and radiation therapy. Flap reconstructions and skin grafting were used in three patients; two patients underwent nasal amputations. Three patients also received postoperative irradiation. Three patients experienced recurrences from 2 to 13 years after the original treatment; there were no deaths related to this tumor. Histologically, these are typically ulcerated tumors seldom showing evidence of in situ carcinoma. Surgical margins of excision were positive or close in three cases but did not influence the chronic course of the disease. No clinical tumor staging system is generally accepted, and it seems that the prognosis for localized disease is good irrespective of clinical stage. Aggressive features, including penetration of cartilage and invasion of overlying skin, may be impressive, but do not preclude long-term survival if bulk disease can be surgically removed.

Carcinoid tumors of the rectum. Silver reactions, fluorescence, and serotonin content of the cytoplasmic granules.

The argyrophil and argentaffin staining reactions of the intracytoplasmic granules of 23 carcinoid tumors of the rectum were studied. The granules were evaluated for the presence of amines by means of formalin-induced fluorescence and an immunoperoxidase method for serotonin. The results indicate that most rectal carcinoids are argyrophil when the more sensitive Grimelius method is employed. Only occasionally are rectal carcinoids argentaffin, a feature that correlates with positive fluorescent reactions and suggests amine content. Of three argentaffin tumors, one stained positively for serotonin, and a second contained clusters of pleomorphic electron-dense granules of the type more typically seen in known amine-containing carcinoid tumors. For practical purposes, the Grimelius argyrophil stain is most useful in confirming a light-microscopic diagnosis of a rectal carcinoid.

Nasopharyngeal carcinoma: antikeratin immunohistochemistry and electron microscopy.

Eighteen examples of nasopharyngeal carcinoma (NPC), a tumor with potential diagnostic difficulty, were studied retrospectively. Using the WHO classification, 16 cases were undifferentiated carcinoma (UC). Immunohistochemistry for each tumor was performed on paraffin sections using two commercially available polyclonal antisera and a monoclonal antibody, AE-1. Method 1 used trypsinization, overnight incubation with the primary antibody and the avidin-biotin complex (ABC) technic. Method 2 used a 20-minute incubation with the primary antibody without trypsinization and employed the peroxidase-antiperoxidase (PAP) technic. Method 2 is the one most frequently employed by pathologists who use immunohistochemistry as a diagnostic aid. Method 1 gave clear positive results in each case with antibody AE-1 and, in most cases, with the polyclonal antisera. Electron microscopy in 10 cases demonstrated desmosomes in each case and easily demonstrable tonofilaments in five. The results of this study indicate that in the diagnosis of UC, the most common variant of NPC, squamous differentiation can be documented readily by electron microscopy and immunohistochemistry for keratin proteins. With the latter, optimization of technic is essential for reliable results.

Occult medullary thyroid carcinoma. Unusual histologic variant presenting with metastatic disease.

A 66-year-old man presented with an enlarged cervical lymph node, interpreted on fine-needle aspiration as squamous cell carcinoma. Histologic assessment of the excised mass demonstrated a mucin-positive glandular neoplasm that, by immunohistochemistry, was positive for carcinoembryonic antigen, calcitonin, and neuron-specific enolase. A subsequent total thyroidectomy revealed a grossly normal organ with a 2-mm microscopic focus of medullary carcinoma and foci of C-cell hyperplasia in the immediate vicinity of the tumor. No amyloid could be demonstrated in either lesion. The diagnostic difficulty encountered in this case is related to the presence of a rare morphologic variant (devoid of amyloid and forming mucin-positive glands) occurring as an occult primary but presenting as a metastasis. Although an occult primary in medullary carcinoma is recognized in familial cases, such a phenomenon is rare in sporadic cases.

Laryngeal cysts in adults: a clinicopathologic study of 20 cases.

Clinically significant cysts in the region of the larynx are uncommon. In this study, 20 cases were recovered for the period 1969-1983. There were eight males and 12 females whose ages ranged from 28-76 years and whose most common symptom combinations were hoarseness (9), local foreign body sensation (5), and pain (4). Laryngoscopic examination revealed cystic lesions 0.5-3.0 cm. in diameter, all localized to the supraglottis with half in the vallecula . Histologically, 17 cysts were closely associated with tonsillar lymphoid tissue. Nine cysts, having squamous lined crypt-like structures and abundant follicular lymphoid tissue, were designated "tonsillar cysts." Eight cysts had a prominent epithelial component and focal follicular lymphoid aggregates. Three cysts were unassociated with lymphoid tissue. Two of these, located in the ventricles of elderly patients, were oncocytic cysts. Both showed oncocytic changes on the surface mucosa and in adjacent salivary gland tissue. In one case, a biopsy of the contralateral ventricle demonstrated oncocytic metaplasia. Treatment in all cases was by surgical excision. Follow-up on 13 patients ranging from three months to 9 years revealed one recurrence of an oncocytic cyst one year after initial removal. We conclude that follicular lymphoid tissue is present in most laryngeal cysts and may play some pathogenetic role in their formation. Furthermore, oncocytic cysts are different from other laryngeal cysts, having a characteristic location, age group, field effect, and recurrence rate.

Systemic rhabdomyosarcoma with diffuse bone marrow involvement. Case report of an unusual presentation.

Rhabdomyosarcoma presenting as a systemic disease is rare. This report concerns a 12-year-old girl who came to medical attention for what was thought to be a hematologic malignancy. Diffuse lytic bone lesions and large primitive cells in the bone marrow exhibiting erythrophagocytosis supported this diagnosis. During the course of the disease, a soft tissue mass in the region of the left ankle was removed and was a typical alveolar rhabdomyosarcoma. Retrospective review of the marrow, including electron microscopy, demonstrated that the primitive marrow cells were probably rhabdomyoblasts as well. The clinical course was a rapid downhill one in which lytic bone lesions and hypercalcemia were prominent. Although rhabdomyosarcoma eventually may disseminate, initial widespread disease without a clinically apparent primary can be a diagnostic dilemma. This clinical presentation, in combination with the recognized aggressiveness of the alveolar histologic subtype, identifies a rare subgroup of patients with rapidly fatal disease.

Electron microscopy in the diagnosis of neuroblastoma.

I review the accumulated knowledge regarding the electron microscopy of neuroblastic tumors using a retrospective study of 13 primarily small cell neoplasms for which the diagnosis of a neuroblastic tumor (neuroblastoma, ganglioneuroblastoma, ganglioneuroma) was either considered or eventually established. A fine fibrillary background, even if focally distributed by light microscopy and seemingly not recovered in the thick sections, correlated with the presence ultrastructurally of neuritic processes bearing dense core ("neurosecretory") granules and lucent vesicles. In three cases without any fibrillary background by light microscopy, granule-bearing processes were not found by electron microscopy, and different diagnoses were subsequently established for two of those cases. From the standpoint of diagnosis, the sampling error normally introduced in ultrastructural examinations has not been reported to be a significant problem, nor was it in the present cases. Therefore, in supporting a light microscopic diagnosis of neuroblastoma, neuritic processes containing dense granules with or without lucent vesicles should be documented. Neuroblastic tumors with evidence of maturity, ie, ganglion cell differentiation, had the best developed morphologic features by both forms of microscopy. Schwann cells were observed in four cases, including one neuroblastoma. The presence of these cells by electron microscopy, although absent by light microscopy, may reflect an early phase of tumor maturation.

Vasitis nodosa. Two cases.

Two cases of vasitis nodosa, one typical example and one unusual case, are presented. The first case was a complication of a previous vasectomy, manifested as a painful nodule at the site of previous surgery, and was associated with sperm granulomas. In the second case, no antecedent vasectomy had been performed, the lesion was located deep in the scrotum, and inflammation was scant. The clinical diagnosis of adenomatoid tumor was also consistent with some aspects of the histopathologic picture. In such cases, the diagnosis of vasitis nodosa can be resolved by finding spermatozoa within the proliferating ductules and individual epithelial cells. Electron microscopy can also be useful in eliminating the possibility that the nature of the proliferating cells is mesothelial. However, the etiology of vasitis nodosa in the absence of previous local traumatic or inflammatory insults remains obscure.

Squamous carcinoma in a major salivary gland: a review of the diagnostic considerations.

CONTEXT: Squamous carcinoma in a major salivary gland has several possible sources: (1) high-grade mucoepidermoid carcinoma, (2) metastasis or direct invasion from a primary skin carcinoma, (3) metastasis from a distant primary carcinoma, or (4) a primary malignant neoplasm. The latter is conventionally regarded as a diagnosis of exclusion after a history of squamous carcinoma elsewhere has been obtained or there is a positive mucin stain. DESIGN: Eleven cases of squamous carcinoma in a major salivary gland are presented and the literature reviewed. RESULTS: Two cases, 1 metastatic from a histologically identical squamous carcinoma from the ipsilateral tonsil and 1 with in situ squamous carcinoma in a duct, demonstrated positive mucicarmine stains. Two cases were high-grade mucoepidermoid carcinomas, also with positive mucin stains. Five cases represented metastases from cutaneous squamous carcinomas. Only 2 cases were regarded as primary carcinomas. There were no histologic clues as to correct subclassification. Six patients died, 4 from their disease. Three of the 5 still alive had recurrence or metastasis. CONCLUSION: The occurrence of squamous carcinoma in a major salivary gland exhibits a histologic sameness that precludes accurate subclassification and assignation of origin. Also irrespective of tumor origin, the clinical approach to diagnosis and treatment is similar. Adjuvant therapy (eg, radical neck dissection, radiation, chemotherapy) is not uniformly applied. Most patients present with a sizable (>3-cm) mass for which total excision is attempted. The natural evolution of the tumor is aggressive, irrespective of clinical context. The traditional subclassification of squamous carcinoma in a major salivary gland may not be clinically relevant.

Breast cancer metastatic to the uterus. Clinical manifestations of a rare event.

Adenocarcinoma of the breast rarely metastasizes to the mucosal surfaces of the uterus. We present two patients with endometrial involvement, in one of whom it was the initial manifestation of her breast cancer. Two additional patients with cervical involvement had abnormal Papanicolaou smears and grossly normal cervices. One of these patients underwent a biopsy, the results of which confirmed metastatic adenocarcinoma. Three of the four patients had previously well-established metastatic disease. The presence of genital, especially mucosal, metastases is indicative of widespread disease and imminent demise. This occurred in one of the patients described here; however, another patient survived 30 months. Breast cancer is a chronic disease for which the metastatic behavior is exceptionally unconventional. Tissue acquired by endometrial curettage or colposcopy may require an awareness on the part of the pathologist to such a clinical circumstance.