Idiopathic hypereosinophilic syndrome with skull base involvement.

Idiopathic hypereosinophilic syndrome (HES) is a heterogeneous disorder characterized by prolonged eosinophilia without an identifiable cause, ultimately resulting in organ dysfunction. Three major types of neurologic involvement have been well defined in HES; however, to our knowledge, inflammatory pseudotumor (IPT) in association with HES has not been reported. We present a case of IPT of the skull base in a patient with HES that suggests that HES may result in an exaggerated immunologic or inflammatory response leading to the formation of IPT.

Endogenous CRF in rat large intestine mediates motor and secretory responses to stress.

BACKGROUND: Corticotropin-releasing factor (CRF) mediates our body's overall responses to stress. The role of central CRF in stress-stimulated colonic motility is well characterized. We hypothesized that transient perturbation in expression of enteric CRF is sufficient to change stress-induced colonic motor and secretory responses. METHODS: Sprague-Dawley rats (adult, male) were subjected to 1-h partial restraint stress (PRS) and euthanized at 0, 4, 8, and 24 h. CRF mRNA and peptide levels in the colon were quantified by real-time RT-PCR, enzyme immuno-assay and immunohistochemistry. Double-stranded RNA (dsRNA) designed to target CRF (dsCRF) was injected into the colonic wall to attain RNA interference-mediated inhibition of CRF mRNA expression. DsRNA for ß-globin was used as a control (dsControl). Four days after dsRNA injection, rats were subjected to 1-h PRS. Fecal output was measured. Ussing chamber techniques were used to assess colonic mucosal ion secretion and transepithelial tissue conductance. KEY RESULTS: Exposure to PRS elevated CRF expression and increased CRF release in the rat colon. Injection of dsCRF inhibited basal CRF expression and prevented the PRS-induced increase in CRF expression, whereas CRF expression in dsControl-injected colons remained high after PRS. In rats treated with dsControl, PRS caused a significant increase in fecal pellet output, colonic baseline ion secretion, and transepithelial tissue conductance. Inhibition of CRF expression in the colon prevented PRS-induced increase in fecal output, baseline ion secretion, and transepithelial tissue conductance. CONCLUSIONS & INFERENCES: These results provide direct evidence that transient perturbation in peripherally expressed CRF prevents colonic responses to stress.

Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.

To evaluate the role of mediastinal irradiation (RT) following surgery for invasive thymomas, a clinical and pathologic review of 117 patients with the diagnosis of thymoma was completed. Fourteen cases were excluded because of the lack of histologic criteria for a thymic tumor, and the remaining 103 were classified according to a staging system as follows: stage I, completely encapsulated (43); stage II, extension through the capsule or pericapsular fat invasion (21); stage III, invasion of adjacent structures (36); and stage IV, thoracic dissemination or metastases (3). The 5-year actuarial survival and relapse-free survival rates were 67% and 100% for stage I, 86% and 58% for stage II, and 69% and 53% for stage III. No recurrences occurred among stage I patients after total resection without RT. However, eight of 21 patients with invasive (stage II or III) thymomas had mediastinal recurrence as the first site of failure following total resection without RT. The 5-year actuarial mediastinal relapse rate of 53% in this group compares unfavorably with the mediastinal relapse rate seen among stage II or III cases following total resection with RT (0%) or following subtotal resection/biopsy with RT (21%). Despite attempted salvage therapy, five of eight patients with mediastinal relapse following total resection alone died of progressive disease. No significant difference was observed in the local relapse rate, overall relapse rate, or survival between those patients undergoing biopsy and RT v subtotal resection and RT for invasive thymomas (stages II and III). Total resection alone appears to be inadequate therapy resulting in an unacceptably high local failure rate with poor salvage therapy results.

Myasthenia gravis and primary squamous cell carcinoma of the thymus: a case report.

We detail a case of primary squamous cell carcinoma of the thymus in a patient with myasthenia gravis. The clinical course of the patient and the gross and histologic appearance of the thymus are discussed. Appropriate therapy for patients with these tumors includes resection of the tumor followed by radiation therapy and continued surveillance for recurrence. Review of the literature indicates less than 50% survival at 10 years and 22% recurrence rate at 5 years for patients with this tumor.

Myeloid metaplasia presenting as a breast mass.

A case of myeloid metaplasia presenting as an isolated breast mass in an elderly woman is described. The breast tumor developed 16 years after the initial diagnosis of myelofibrosis and was the only clinically significant sign of the disease necessitating treatment. Ultrastructural examination demonstrated that the lesion consisted of megakaryocytes and immature myeloid cells. This rare lesion, one of a number of manifestations of hematopoietic diseases involving the breast, should be included in the differential diagnosis of stromal breast lesions, especially those containing giant cells.

The immunohistochemistry of gastrointestinal stromal tumors. Evidence supporting an origin from smooth muscle.

To study the histogenesis of gastrointestinal stromal tumors, 79 cases were evaluated for desmin (DES), vimentin (VIM), and S-100 protein immunoreactivity by the avidin-biotin immunoperoxidase procedure on paraffin-embedded, Bouin's-fixed tissue sections. All tumors showed weak vimentin positivity. Trapped non-neoplastic smooth muscle and nerve twigs were often noted, particularly at the tumor periphery. Significant tumor S-100 positivity was not identified in our series. Similarly, glial fibrillary acidic protein (GFAP) immunoreactivity (performed in 11 desmin-negative tumors) was not detected within either gastrointestinal stromal tumors or enteric glial cells. Fifty-three percent (53%) of all gastrointestinal stromal tumors (GIST) displayed positive tumor cell desmin immunoreactivity. All 10 esophageal and all four colorectal tumors were diffusely desmin positive and unequivocal smooth muscle lesions. In contrast, only 17 of 37 (46%) benign and six of nine (67%) malignant gastric tumors were desmin positive. Similarly, four of 10 (40%) benign and one of nine (11%) malignant small-bowel tumors expressed desmin. Several gastric neoplasms with prominent nuclear palisading resembling schwannian Antoni A regions were nonetheless desmin positive. Epithelioid gastric tumors were more frequently desmin positive than nonepithelioid tumors; however, this positivity did not attain statistical significance. Two gastrointestinal stromal tumors that were desmin negative in paraffin-embedded material had detectable antigen in frozen sections. Gastric and small-bowel tumors measuring less than 3 cm were significantly more often desmin positive than those 3 cm or greater. We conclude that the method of fixation, tissue preparation, and immunostaining may significantly affect the expression of desmin. Although the histogenesis of gastrointestinal stromal tumors remains controversial, most of these tumors show evidence of smooth muscle differentiation.

Immunoperoxidase localization of secretory component in reactive mesothelium and mesotheliomas.

Immunoperoxidase localization of the secretory component (SC) of immunoglobulin (Ig) A was undertaken on paraffin-embedded tissue to investigate its usefulness in differentiating epithelial from mesothelial neoplasms. Epithelial cells, but not mesothelial cells, have been previously reported to contain SC, which may be involved in the intraepithelial transport of secretory IgA. In this study we report, for the first time, focal but unequivocal staining for SC in reactive mesothelium and mesotheliomas (10/16). Reactivity was not associated with any histologic subtype of malignant mesothelioma although staining was usually seen in the "epithelial" type. The significance in terms of possible mesothelial secretory IgA transport is discussed.

Immunohistochemistry of soft tissue tumors: progress and prospects.

The immunohistochemical definition of soft tissue tumors has only begun (table 1). A number of antigens described here play a role in diagnostic pathology, and a few have been shown to be specific markers for certain types of cell differentiation. The detection of a wide variety of antigens in soft tissue sarcomas may initially prove confusing in some areas. For example, when specific markers are used, multidirectional differentiation in a tumor may be found more frequently than it is now, making more sarcomas actually "mesenchymomas." In such situations, certain types of differentiation may imply more or less aggressive behavior. It is also possible that panels of different immunohistochemical reagents may be required to determine a specific histogenesis. Furthermore, interpretive caution is clearly necessary, since many sarcomas contain normal tissues. Owing to the aggressive nature of sarcomas, more information on their biochemical composition will be required for proper diagnosis and clinical management. As pathologists, we are in a key position to contribute to the understanding of these tumors. In-situ biochemical analysis of sarcomas making use of immunohistochemical methodology is a powerful tool in the investigation of the difficult problems of histogenesis, tumor heterogeneity, and biologic potential.

Malignant epithelioid vascular tumors of the pleura: report of a series and literature review.

Primary malignant vascular tumors of the pleura are rare. The significance and difficulty of distinction between pleural epithelioid hemangioendothelioma (EHE) and angiosarcoma have not yet been addressed. A new series of pleural angiosarcoma is reported, and the relevant literature is reviewed. Five cases were identified from files of the authors' institutions and personal consultation cases (J.J.B.). Twenty-six cases of primary malignant vascular tumors of the pleura were identified in the literature. In a total of 31 cases, 22 were from the West and 9 from Japan. Patients were 22 to 79 years old (average, 57), and the male/female ratio was 9:1. Prior chronic pyothorax was identified only in cases reported from Japan. History of exposure to radiation or asbestos was noted in a few Western cases. The most common presentation was pleural thickening and effusion. Almost all of the patients died of disease shortly after diagnosis. A spectrum of histology ranging from characteristic high-grade epithelioid to relatively low-grade EHE-like features was observed in our cases and can be found in previous reports. Most cases showed variable spotty cytokeratin immunoreactivity. Endothelial markers (factor 8, CD34, or CD31) were invariably positive. Pleural angiosarcomas are often epithelioid and can be easily mistaken for mesothelioma or carcinoma clinically and histologically. Awareness of this rare tumor should prompt the use of endothelial markers when faced with a questionable mesothelioma. When cytokeratin is negative, or focal with strong vimentin reactivity, a vascular tumor should be suspected and confirmed with vascular markers. Because of their invariably aggressive behavior, all epithelioid vascular tumors of the pleura should be considered highly malignant regardless of the presence of EHE-like histological features.

Massive localized lymphedema: additional locations and association with hypothyroidism.

We report the second series of a new entity called "massive localized lymphedema in morbidly obese patients" (MLL), recently described in medical literature. Our 6 cases present additional locations as well as an association with hypothyroidism. Huge masses, of longstanding duration ranging from 9 months to 8 years, afflicted the thigh, popliteal fossa, scrotum, suprapubic and inguinal region, and abdomen of morbidly obese adults. Although clinical impressions were generally of a benign process, including lipoma and recurrent cellulitis, the possibility of a malignant neoplasm could not be eliminated. Poorly defined and non-encapsulated, these skin and subcutaneous lesions were most remarkable for their sheer size, measuring 50.6 cm in mean diameter (range, 38-75 cm) and weighing a mean of 6764.5 g (range, 2,060-12,000 g) The overlying skin exhibited the induration and peau d'orange characteristic of chronic lymphedema. Grossly and histologically, a prominent marbled appearance, rendered by fibrous bands intersecting lobules of adipose tissue, simulated sclerosing well differentiated liposarcoma. However, the absence of atypical stromal cells, atypical adipocytes, and lipoblasts precluded the diagnosis of well differentiated liposarcoma. Instead, reactive features, encompassing lymphatic vascular ectasia, mononuclear cell infiltrates, fibrosis, and edema between the collagen fibers, as well as ischemic changes including infarction and fat necrosis, established the diagnosis of MLL. Although the pathogenesis of MLL may be as simple as obstruction of efferent lymphatic flow by a massive abdominal pannus and/or prior surgery, the presence of hypothyroidism in 2 of our patients suggests an alternative pathogenesis. Recognition of this entity by both clinicians and pathologists should avert a misdiagnosis as a low-grade liposarcoma.

Cortical versus medullary thymomas: a useful morphologic distinction?

We have tested the hypothesis that thymomas can be classified solely on the basis of epithelial cell morphology and that this distinction is prognostically useful. One hundred thymic epithelial tumors were classified according to the morphologic resemblance to cortical or medullary thymic epithelium and to the traditional classification (lymphocytic, epithelial, mixed, and spindled). Follow-up data was obtained on 78 patients. Fifty-eight percent of the tumors were invasive. Nineteen of the invasive tumors relapsed and none of the non-invasive tumors relapsed (P less than .0001). Four of nine tumors with microscopic invasion through the capsule recurred. Statistical analysis showed no significant differences in relapse-free survival for any of the histologic categories. Ninety-four percent of the tumors studied were keratin positive and all were chromogranin negative. Carcinoembryonic antigen was negative for all but one cytologically malignant tumor; of the tumors 75% were epithelial membrane antigen positive, 80% were Leu-7 positive, and 11% were neuron specific enolase positive. Seven of 12 tumors tested expressed HLA-DR. There was no correlation between immunoreactivity and classification. The morphologic cortical/medullary distinction is conceptually attractive but appears clinically to be no more advantageous than the traditional classification.

Immunoreactive secretory component of IgA in human tissues and tumors.

Secretory component (SC) of IgA is known to be produced by many glandular epithelial cells. To assess the usefulness of this antigen as a glandular tumor differentiation marker, the authors evaluated its normal body distribution and tested a variety of glandular neoplasms. The known normal distribution of SC was confirmed and extended to include the prostate. Immunoreactive SC was detected only in epithelial and glandular tumors. Many types of well-differentiated adenocarcinomas, (ovary, prostate, small bowel, pancreas, stomach, biliary) however, contained little or no immunoreactive SC. Therefore, the authors conclude that immunoreactive SC cannot be used as a general differentiation marker in tumors of glandular derivation. A high frequency of antigenic expression was found in adenocarcinomas of the lung (4/10), breast (5/10), and colon (24/27). No correlation between expression and tumor differentiation was observed in pulmonary or mammary tumors. Only in colonic neoplasia was such a relationship detected. SC expression in colonic tumors was not related to mucin content but was associated with the presence of a visible brush border.

Use of a "pneumatic" tube in anatomic pathology.

In anticipation of the temporary relocation of Surgical Pathology some distance from the operating rooms, a "pneumatic" tube system was installed to transport fresh tissue from surgery to pathology at the Hospital of the University of Pennsylvania. The point-to-point 4-inch internal diameter system is actually of the blower or "pea-shooter" type. Side-opening carriers were preferred, and electronic sensors were installed for monitoring and safety. At the pathology end of the system, a complete panel of electrical controls exist that are capable of initiating the blower at either end, enabling full control. For possible future retrieval of stuck carriers, several points of mechanical entry were desired and constructed. The transit time over 886 feet varies with the weight of the specimen but averages 25-35 seconds. Thus far, after 32 months and 12,652 transits, no specimens have been lost or damaged. During the first few months, two specimens became stuck for reasons relating to human error but were easily retrieved. This system, in conjunction with operating room telephone intercoms, has become fully accepted and trusted by surgeons and pathologists.

Anaplastic thyroid tumors. Immunohistology.

Using an avidin-biotin immunoperoxidase technic, the authors studied 29 anaplastic thyroid tumors (ATTs) to determine the frequency of hormonal (thyroglobulin--TG; calcitonin--CT), epithelial (epithelial membrane antigen, monoclonal keratin), or sarcoma (desmin; alpha-1-antichymotrypsin--ACT; vimentin) markers. Their results indicate that 27% of ATTs stain for TG and none for CT. Fifty-five percent showed epithelial markers, 48% marked for ACT, and 47% for vimentin. Coexpression of keratin and vimentin was found in 39% of cases tested. The expression of the tested antigens did not correlate significantly with histologic pattern (epithelial vs. "sarcomatous"). Of note is the fact that 30% of the ATTs the authors tested expressed none of the markers they examined, indicating total lack of differentiation.

Leu M1 and S100 in Hodgkin's disease and non-Hodgkin's lymphomas.

Leu M1 positivity of Reed-Sternberg (RS) cells has been reported. The authors studied the specificity and sensitivity of Leu M1 in Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Within NHL, they particularly selected cases that were confused with HD. The authors also studied S100 antigen to determine the pattern of staining in HD and NHL. Paraffin-embedded sections of 23 HD cases (3 lymphocyte predominate, 10 nodular sclerosing, 10 mixed cellularity) and 22 NHL cases (13 diffuse large cell, 5 diffuse mixed small and large cell, 4 others) were studied using an ABC technic. In 20 of 23 HD cases, RS cells and variants were Leu M1+; most cases contained prominent paranuclear positivity; some had diffuse cytoplasmic staining; and some had apparent staining of the cell surface. Neutrophils were intensely positive for Leu M1 and occasional histiocytes also were labeled. In two of the three negative cases (MC), the neutrophils were only weakly positive, thus suggesting a problem with tissue preparation. Of 22 NHL cases, 15 were totally Leu M1 negative. In six cases, rare or occasional tumor cells contained Leu M1 positivity in either a weak punctate, granular, or surface pattern. In an additional case, extensive pleomorphic cell staining was seen indistinguishable from that observed in RS cells; this case was the fourth recurrence of a primary skin NHL which began two years earlier as a pure small cleaved cell NHL. A total of three cases had positive pleomorphic cells. Some carcinomas were also Leu M1 positive. Concerning S100 antigen, the authors found scattered non-neoplastic cells throughout both HD and NHL samples; no tumor cells stained with this antigen. The negative S100 reaction of RS cells fails to support the argument for a dendritic cell origin. In properly prepared tissue, Leu M1 staining is quite sensitive for RS cells and variants, displaying a characteristic pattern. However, occasional Leu M1 positivity identified in NHL raises doubt as to its complete specificity.

Malignant granular cell tumors: report of a case and review of the literature.

BACKGROUND: Granular cell tumors are uncommon soft tissue tumors and are more commonly benign. Malignant granular cell tumors are extremely rare, may be confused with other soft tissue sarcomas, and can be diagnosed only when metastatic disease that has the same histologic features as the primary tumor has been identified. Metastases are more commonly seen in lymph nodes and lungs; however, often the metastatic disease is not identified at the time of initial diagnosis and presents anywhere from 3 to 37 months after initial treatment. Certain findings, such as histologic appearance and size, may suggest that a granular cell tumor has uncertain malignant potential. METHODS: We evaluated a patient with a granular cell tumor of uncertain malignant potential of the left chest wall and no evidence of metastatic disease on physical examination with a preoperative work-up to identify sites of occult disease. RESULTS: The patient was found to have suspicious ipsilateral axillary adenopathy on magnetic resonance imaging and computed tomography scan. No other regional or distant disease was identified. The patient underwent an en bloc wide excision and axillary lymph node dissection. Metastatic disease was identified in nine of 23 lymph nodes. CONCLUSIONS: Patients who are diagnosed with a granular cell tumor of uncertain malignant potential may benefit from preoperative radiologic evaluation because occult metastatic disease may be identified, alter the surgical approach, and possibly affect the long-term outcome.

Nodular fasciitis of the vulva: a report of two cases.

We describe two patients with nodular fasciitis of the vulva, a benign pseudoneoplastic lesion that can histologically mimic sarcoma.

Granulomatous salpingitis secondary to Crohn's disease.

A 30-year-old woman with longstanding Crohn's disease underwent resection of bowel and adherent adnexa. Granulomatous enterocolitis and granulomatous salpingitis and oophoritis were present histologically. Unusual features accompanying this tubal process included formation of an adnexal mass and florid atypical proliferation of the tubal epithelium. This proliferation is similar to that epithelial change described in tuberculous salpingitis and should not be confused with carcinoma in situ.

A novel t(1;8)(p13;p11) in a thymic carcinoma with unusual giant cell features and renal metastasis.

Cytogenetic analysis of a thymic carcinoma metastatic to the left kidney revealed the presence of a t(1;8)(p13;p11). In addition to a previously undescribed translocation, this tumor histologically showed unusual giant cell features.

Benign glandular schwannoma.

The vast majority of reported glandular schwannomas, the rarest type of divergent differentiation in nerve sheath neoplasms, have been malignant tumors. We describe a benign glandular schwannoma, less than 1 cm in diameter, that developed in the deep subcutaneous region of the left flank of a 36-year-old woman. The glandular component occurred as a single large cyst with an undulating lining occupying the central one third of the lesion and was lined in large part by a well-oriented, flattened, single cell layer of cuboidal to low columnar cells with a basement membrane. This extremely unusual lesion, apparently the fourth benign instance reported, is important for several reasons: (1) it does not appear to be a result of inclusion of previously postulated dermal adnexal glands; (2) it further establishes the existence of a true benign counterpart of the glandular schwannoma, of which pathologists should be aware; (3) it can be distinguished from the recently reported pseudoglandular schwannoma; and (4) it lends additional support to the concept of a direct metaplastic origin of the epithelial element from the schwannian component because of the focal presence of a maloriented pseudoglandular element.