Clinicopathologic analysis of CD10+ and CD10- diffuse large B-cell lymphoma. Identification of a high-risk subset with coexpression of CD10 and bcl-2.

We analyzed 53 cases of diffuse large B-cell lymphoma (DLBCL) to determine whether expression of CD10 is a relevant biologic parameter. Tumor morphologic features were assessed semiquantitatively. Bcl-2 protein expression was studied by immunohistochemical analysis. The presence or absence of CD10 by flow cytometry was correlated with clinical and pathologic characteristics. CD10+ (23 cases) and CD10- (30 cases) DLBCLs were indistinguishable based on age, sex, extranodal presentation, B symptoms, clinical stage, morphologic features, or bcl-2 expression. However, cases with a CD10+ phenotype showed a significantly lower rate of complete remission. Cases expressing bcl-2 showed trends toward a lower rate of complete remission and poorer overall survival. Examination of CD10 and bcl-2 interaction revealed that the prognostic effects for both of these antigens were due to a subset of CD10+ bcl-2-positive cases. Compared with cases expressing one or neither of these markers, patients with dual-positive tumors had a poorer complete response rate to initial therapy and strikingly worse overall survival. While CD10+ and CD10- DLBCLs are similar with regard to a variety of clinical and pathologic features, CD10 and bcl-2 coexpressing tumors are an extremely high-risk subset based on response to therapy and overall survival.

Cutaneous angiosarcoma complicating morbid obesity.

Herein, we report a case of cutaneous angiosarcoma in a 35-year-old, morbidly obese woman. The tumor arose in the most dependent portion of the lower abdominal panniculus and showed typical changes of chronic lymphedema. The patient underwent a radical resection of her lower abdominal wall panniculus, which showed a multicentric, high-grade angiosarcoma with bilateral superficial inguinal lymph node metastases. Histologically, conventional vasoformative areas were admixed with poorly differentiated sheets of spindle and epithelioid cells. Factor VIII was focally positive (membranous), whereas CD31 showed robust, diffuse positivity (membranous and cytoplasmic). The initial margins of resection were negative, and no follow-up radiation or chemotherapy was given. Following a recurrence at the previous excision site, the patient died 7 months after the surgery. Postmortem examination revealed a widely metastatic tumor that involved multiple organ systems. We believe this is the second report of cutaneous angiosarcoma occurring in a chronically lymphedematous abdominal panniculus due to morbid obesity.

Loss of Dpc4 expression in colonic adenocarcinomas correlates with the presence of metastatic disease.

DPC4 is a candidate tumor suppressor gene on chromosome 18q21, a region that shows high frequencies of allelic losses in pancreatic and colorectal adenocarcinomas. Biallelic inactivation of DPC4 has been reported in half of pancreatic cancers, but are relatively infrequent in other tumor types. The role of DPC4 inactivation in colorectal neoplasms has not been fully characterized. An immunohistochemical assay for Dpc4 protein expression has been recently developed and shown to be a sensitive and specific surrogate for alterations in the DPC4 gene. In this study we examined the expression of Dpc4 protein in formalin-fixed archival tissue from 83 colorectal lesions, including 19 adenomas and 64 sporadic adenocarcinomas (11 stage I, 13 stage II, 17 stage III, and 23 stage IV cancers). None of the adenomas or stage I adenocarcinomas showed loss of Dpc4 expression, whereas one of 13 (8%) stage II, one of 17 (6%) stage III, and five of 23 (22%) of stage IV cancers showed loss of Dpc4 expression. There was a borderline significant difference in loss of Dpc4 reactivity in colorectal tumors with distant metastasis at presentation (22%) versus primary tumors without distant metastasis (5%) (Fisher's exact test, P = 0.05; chi(2) = 0.04). Poorly differentiated histology or status of pericolonic lymph nodes did not affect Dpc4 expression. Alterations in DPC4 are involved in the progression of a subset of colorectal carcinomas, especially those that present with advanced disease. In the sequential pathogenesis of colorectal tumors, inactivation of DPC4 is likely to be a late event.

Expression of the human mismatch repair gene hMSH2: a potential marker for urothelial malignancy.

BACKGROUND: The human mismatch repair (MMR) gene hMSH2 (human mutS homolog-2) is a DNA repair gene that has been reported to be mutated in 40% of hereditary nonpolyposis colon cancer (HNPCC) kindreds and a small percentage of sporadic tumors. HNPCC is a cancer predisposition syndrome with an increased risk of carcinoma of the colon, endometrium, stomach, small intestine, ovary, ureter, and renal pelvis. Immunohistochemical analysis demonstrated increased hMSH2 expression in sporadic colon carcinoma and in the replicative compartment of normal epithelium. A recent immunohistochemical analysis of hMSH2 in bladder tumors correlated reduced hMSH2 expression with recurrence and higher tumor grade. In the current study, we examined hMSH2 expression in urothelial malignancy using immunohistochemical analysis and developed a molecular assay for the detection of hMSH2 expression in bladder washes. METHODS: Immunohistochemical analysis of 17 tumors from the genitourinary tract and reverse transcription coupled with polymerase chain reaction (RT-PCR) of 40 bladder washes were used to investigate hMSH2 expression in noninvasive and invasive urothelial malignancies. RESULTS: Increased expression of hMSH2 was detected in all tumors examined using immunohistochemical analysis independent of grade or stage. Reverse transcription-PCR of hMSH2 mRNA from bladder washes detected 17 of 21 patients with primary or recurrent urothelial neoplasms or tumors involving the urothelial system. Four patients with urothelial malignancies without detectable hMSH2 expression from their bladder washes had high grade lesions. Ten of 13 patients without pathologic or cystoscopic evidence of bladder tumors were negative for hMSH2 expression in bladder washes. Two patients with bladder tumors and bladder washes that were positive for hMSH2 subsequently were found to be negative for hMSH2 after treatment of their tumors and at last follow-up had remained recurrence free for at least 1 year. CONCLUSIONS: The results of the current study suggest that hMSH2 expression is increased in low and high grade urothelial neoplasms, similar to the expression pattern in sporadic colon carcinoma. However, a fraction of high grade lesions may not express hMSH2 as detected by RT-PCR from bladder washes. The ability to detect hMSH2 expression in bladder washes may allow the use of hMSH2 expression as a marker for urothelial malignancy. In addition, the ability to define hMSH2 deficient tumors using bladder washes may have prognostic significance in the treatment of patients with urothelial carcinoma.

Endometrioid carcinoma arising in pericecal endometriosis clinically mimicking Crohn's disease.

A case of endometrioid carcinoma arising in pericecal endometriosis that clinically and radiologically mimicked Crohn's disease is presented. After developing several complications of steroid therapy for presumed Crohn's disease, a 48-year-old woman developed intestinal obstruction and underwent a right hemicolectomy. A pericecal mass composed of endometriosis and endometrioid carcinoma and a locally metastatic ileal carcinoid tumor were resected. The patient recovered fully and is clinically free of tumor at 36 months. The pertinent literature is reviewed and the etiologic, therapeutic, and prognostic implications of this case are discussed.

Fine Needle Aspiration Cytology and Histologic Findings of Granular Cell Tumor of the Breast: Review of 19 Cases with Clinical/Radiologic Correlation.

Granular cell tumors (GCTs) are rare lesions in the breast of putative schwannian origin. These tumors are found in multiple sites throughout the body and have a characteristic histologic appearance. Recognition of these usually benign tumors is important since clinically, radiologically, and grossly GCTs of the breast often mimic carcinoma. The literature on these lesions in the breast is confined to isolated case reports. We describe the epidemiologic, cytologic, pathologic, and radiologic findings in 19 GCTs of the breast in 16 patients diagnosed at the University of Texas Southwestern Medical Center between 1991 and 1997.

Solitary metastasis of renal cell carcinoma to the contralateral adrenal gland 22 years after nephrectomy.

A case of solitary metastasis to the contralateral adrenal 22 years after radical nephrectomy for renal cell carcinoma (RCC) is described. This case highlights the variable behavior of RCC, the tendency for adrenal metastasis, and the potential for prolonged survival after resection of late solitary metastases.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas and periampullary region.

BACKGROUND: Undifferentiated carcinomas with osteoclast-like giant cells are rare pancreatic and periampulary neoplasms that morphologically mimic giant cell tumor of bone. Despite numerous publications based primarily on single case reports, the terminology, histogenesis, and biologic behavior of these tumors remain controversial. METHODS: The authors studied one periampullary and nine pancreatic neoplasms of this type. Immunohistochemistry was performed on nine of the cases and clinical follow-up data was obtained in eight. RESULTS: The neoplasms were large (average 9 cm), partially or completely multicystic, and hemorrhagic. Histologically, they were composed predominantly of ovoid or spindle-shaped bland mononuclear cells and evenly spaced osteoclast-like giant cells. However, three neoplasms had foci in which the nuclear pleomorphism of the mononuclear cells approached that observed in anaplastic spindle and giant cell carcinomas. Other histologic features included phagocytosis of the mononuclear cells by the osteoclast-like giant cells (in 7 of 10 cases), osteoid or bone formation (in 3 of 10 cases), and chondroid differentiation (in 1 of 10 cases). Four neoplasms had foci of conventional adenocarcinoma and two arose in preexisting mucinous cystic neoplasms of the pancreas. The mononuclear cells were positive for epithelial markers in six of nine tumors tested (cytokeratins AE-1, AE-3, Cam 5.2, and/or epithelial membrane antigen). They were negative for the histiocytic markers (CD-68, lysozyme) in all nine cases tested. In contrast, the osteoclast-like giant cells were positive for CD-68 in all nine cases, positive for lysozyme in four cases, and negative for cytokeratins (AE-1, AE-3, and Cam 5.2) in all nine cases. p53 stained the mononuclear tumor cells in three cases and MIB-1 stained the mononuclear tumor cells in four cases, but the osteoclast-like giant cells did not stain with either antibody in all nine cases tested. Most of the patients died of disease within 1 year of diagnosis; only 1 patient was alive and disease free 14 years after surgical excision. CONCLUSIONS: The association of these tumors with conventional adenocarcinoma or mucinous cystic neoplasms, the histologic features, and the immunohistochemical profile supports an epithelial phenotype for the mononuclear cells and a reactive histiocytic lineage for the nonneoplastic osteoclast-like giant cells. These neoplasms, which are better classified as undifferentiated carcinomas, follow an aggressive clinical course; most patients die of disease within 1 year.

Ectopic prostatic tissue in the uterine cervix.

This is the first reported case of ectopic prostatic tissue in the uterine cervix, diagnosed in a 38-year-old woman. A cluster of benign prostatic glands with cribriform and papillary patterns and focal squamous metaplasia occupied the superficial endocervical stroma. The glands were immunoreactive for prostatic specific antigen and prostatic specific acid phosphatase. This lesion, which could be confused with microglandular hyperplasia, mesonephric rests, or adenocarcinoma in situ may represent an embryonic rest.

K-ras mutations and allelic loss at 5q and 18q in the development of human pancreatic cancers.

CONCLUSION: Our findings have implications for early diagnosis and for the identification of patients at increased risk. BACKGROUND: Invasive cancers of the pancreas frequently are preceded by and associated with a spectrum of preneoplastic changes. We investigate the presence of K-ras mutations and allelic loss at 5q and 18q loci in preneoplastic lesions associated with nine cases of invasive pancreatic ductal carcinomas. METHODS: We precisely microdissected 115 foci of normal, preinvasive, and invasive foci from paraffin-embedded sections. RESULTS: 1. K-ras mutations occur early in the pathogenesis of pancreatic adenocarcinoma. Mutations were identified in multiple preneoplastic foci associated with al six cases in which ras mutations were present in the corresponding invasive cancers, including nearly all foci of mucous cell and atypical hyperplasia, in some cases of papillary hyperplasia (40%), and in one example of morphologically normal epithelium. 2. Ras mutations in preneoplastic foci are widespread, occur distant from the invasive tumor, and may present multiple mutations. Two, and in one case three, different types of K-ras mutations were found in separate preneoplastic foci from three individual cases. 3. Evidence for a "second hit" in the ras gene (i.e., loss of wild-type allele or amplification of the mutant allele) was present in some tumors and may be associated with the invasive process. 4. In contrast to ras mutations, limited data suggest that loss of heterozygosity (LOH) at 5q and 18q are relatively late events.

Atypical carcinoid of the esophagus: a case report and review of the literature.

BACKGROUND: Although carcinoid tumors of the gastrointestinal tract are relatively common, their occurrence in the esophagus is exceedingly rare. The authors report a case of an atypical carcinoid presenting in the cervical esophagus of an 82-year-old woman. METHODS: The tumor was studied with routine, silver, and immunohistochemical techniques for cytokeratin, chromogranin, and various secretory products. In addition, the literature was reviewed for carcinoid tumors of the esophagus and the findings summarized. RESULTS: The esophageal tumor showed focal necrosis, atypical cytologic features, and increased mitotic activity. It stained diffusely for chromogranin and focally for serotonin; thus it was considered an atypical carcinoid. The patient was free of disease 9 months after excision. On review of the literature, 13 additional cases of esophageal carcinoid were found. The average age of the patients was 60 years with a male predominance of 6:1; the most common presenting symptoms included dysphagia and weight loss. The majority of tumors occurred in the submucosa of the lower esophagus, and ranged in size from 1 to 12 cm. All patients except one had surgical treatment, three received adjuvant radiotherapy or chemotherapy. Although follow-up was limited, survival correlated with stage; seven of ten Stage I or II patients were disease free whereas three of four Stage III or IV patients had died of disease; the fourth patient is alive with brain metastases. CONCLUSIONS: Esophageal carcinoid tumors are exceedingly rare neoplasms. They usually occur in the lower esophagus of males who present with dysphagia. Survival statistics are limited, but appear best correlated with disease stage.

Unusual malignant epithelial tumors of the gallbladder.

Most malignant epithelial tumors of the gallbladder are heterogenous and classified as adenocarcinomas. The authors report a previously unrecognized group of unusual gallbladder carcinomas including two cases of signet ring cell carcinoma in situ, three of cribriform invasive adenocarcinoma, and one of adenocarcinoma with pseudoangiosarcomatous features. In addition, the authors review their material and update the information on clear cell, small cell, and undifferentiated carcinoma of the gallbladder. A new morphologic variant of undifferentiated carcinoma mimicking lobular carcinoma of the breast is identified. The clinical, morphologic, and immunohistochemical features of these unusual neoplasms are emphasized.

Increased expression of early growth response-1 messenger ribonucleic acid in prostatic adenocarcinoma.

PURPOSE: We isolated genes whose expression differs between normal and malignant prostate. MATERIALS AND METHODS: Differential display polymerase chain reactions revealed a messenger ribonucleic acid (mRNA) with higher expression in prostatic adenocarcinoma versus age matched normal tissue. Deoxyribonucleic acid sequencing identified this mRNA as the product of the early growth response-1 gene. RESULTS: Early growth response-1 mRNA levels were elevated in 12 of 12 intraprostatic adenocarcinomas but not in breast or ovarian cancers, or in rapidly dividing rat ventral prostate cells. Early growth response-1 mRNA was detected in epithelial and stromal cells at tumor margins but not in lymph node metastases. CONCLUSIONS: Early growth response-1, a nuclear transcription factor, is implicated in the growth and invasion of intraprostatic cancers.

Physiologic versus neoplastic C-cell hyperplasia of the thyroid: separation of distinct histologic and biologic entities.

BACKGROUND: Although hyperplasia of C-cells has been described in association with various pathologic and physiologic conditions, criteria for its diagnosis are poorly defined. Both neoplastic and physiologic C-cell proliferations have been lumped together under the umbrella designation of C-cell hyperplasia (CCH), creating considerable confusion among clinicians and pathologists. METHODS: in order to compare the morphologic and immunohistochemical characteristics of the two major types of CCH, we examined thyroid sections of 17 patients with familial forms of C-cell hyperplasia and/or neoplasia and tissue sections of 19 thyroid glands known to have reactive or physiologic CCH (at least 50 C-cells per one low power field, 100X). Hematoxylin and eosin (H & E) stained sections and immunohistochemical stains for calcitonin were assessed in each case. RESULTS: Physiologic or reactive CCH was not recognized with certainty on H & E stains in any of the cases due to morphologic similarities between C-cells and adjacent follicular cells. Detection of this form of hyperplasia, which was predominantly diffuse, required calcitonin immunostains and quantitative analysis. Conversely, nodular and diffuse neoplastic CCH was easily identified with conventional H & E stains at the periphery of 11/12 (92%) familial medullary thyroid carcinomas (MTC). In the other five cases, neoplastic C-cell hyperplasia was the only pathologic finding on thyroidectomy performed for elevated serum calcitonin levels detected via provocative biochemical screening or identification of the mutated RET proto-oncogene by genetic analysis. The C-cells in this neoplastic form of CCH were large, mildly to moderately atypical, and confined within the basement membrane of thyroid follicles. Moreover, these cells were cytologically indistinguishable from those of invasive MTC cells. CONCLUSIONS: Physiologic and neoplastic CCH are biologically and morphologically distinct entities. The former cannot be recognized with certainty with conventional stains and requires immunohistochemistry and quantitative analysis for diagnosis. The latter consists of mildly to moderately atypical C-cells that can be identified with H & E stained sections. Consequently, the number of C-cells is of no importance for the diagnosis of neoplastic CCH which is considered to be the precursor (medullary carcinoma in situ) of invasive medullary carcinoma.

False-positive serum prostate-specific antigen values in a patient with non-Hodgkin lymphoma of the kidney.

Prostate-specific antigen (PSA) is the clinically most useful tumor marker for prostate cancer. Although false-positive elevations have been reported due to disease processes outside the prostate gland with the use of the polyclonal assay, such false-positive test results have been exceedingly rare with the use of the monoclonal assay. We report the case of a patient diagnosed with a B-cell lymphoma of the kidney and a significant elevation of serum PSA levels by monoclonal assay in the absence of either inflammatory or malignant prostate disease. PSA returned to normal during lymphoma-specific chemotherapy with a cyclophosphamide, mechlorethamine, vincristine, procarbazine, prednisone regimen. Possible explanations and clinical implications are discussed.

Primary leiomyosarcoma of the seminal vesicle.

A case of leiomyosarcoma of the seminal vesicle is described in a 68-year-old man. Digital rectal examination and pelvic computed tomography (CT) scan disclosed a large pelvic mass in the region of the prostate, whereas magnetic resonance imaging (MRI) suggested that the mass arose from the right seminal vesicle. Biopsy of the mass revealed a high-grade malignancy, thus a radical cystoprostatectomy was performed. Pathologic examination revealed a leiomyosarcoma arising from the right seminal vesicle. The patient is well and free of recurrent disease 13 months following surgery.

Cutaneous endometriosis as a diagnostic pitfall of fine needle aspiration biopsy. A report of three cases.

We describe the cytologic features of three cases of cutaneous endometriosis in young women (average age, 27 years); two cases presented as lower abdominal nodules associated with a previous cesarean section scar. The third case presented as a 5 x 4-cm inguinal mass. The smears were generally cellular, consisting of epithelial and stromal fragments. Epithelial cells showed large, hyperchromatic nuclei and moderate amounts of cytoplasm, with considerable nuclear overlapping. The stromal aggregates also showed crowded, overlapping nuclei and scant, admixed, hemosiderin-laden macrophages. These features, combined with isolated cells in the background, made differentiation from metastatic carcinoma extremely difficult. Cutaneous endometriosis can present a diagnostic pitfall on fine needle aspiration, especially in the absence of a previous history of abdominal surgery or established diagnosis of endometriosis.

Crystalloids in metastatic prostatic adenocarcinoma.

The authors report a case of metastatic prostate cancer masquerading as a primary lung tumor. Histologically, the lung tumor displayed eosinophilic crystalloids in the malignant glands typical of those previously described in prostatic adenocarcinoma. Review of histologic material from 30 additional patients with metastatic prostate cancer failed to reveal crystalloids in the metastases. Seven patients with histologic material from locally advanced prostatic adenocarcinoma, defined as spread to the rectum, bladder, or nonnodal pelvic soft tissue, were also reviewed. One of these patients demonstrated crystalloids in the bladder extension of locally advanced prostatic adenocarcinoma. Although rare, the presence of crystalloids may be used as strong evidence for the prostatic origin of an adenocarcinoma of uncertain origin.

Hyalinizing trabecular carcinoma of the thyroid gland.

We report four unusual cases of hyalinizing trabecular thyroid tumors, three of which displayed capsular and/or blood vessel invasion and were classified as minimally invasive carcinomas. These three patients were all euthyroid women aged 18, 39, and 62 years. The youngest patient also had familial polyposis, while the oldest patient was being followed for Hashimoto's thyroiditis. All three lesions were solitary nodules, were "cold" by radioactive iodine thyroid scan, and ranged from 2.5 to 4.0 cm in diameter. The tumors were encapsulated and had growth patterns and cytologic features similar to those described for hyalinizing trabecular adenomas. In fact, the only difference between these minimally invasive hyalinizing trabecular carcinomas and the corresponding adenomas was the presence of capsular invasion in all three of the cases and vascular invasion in two. All three patients are free of recurrent or metastatic disease at 1 to 2 years' follow-up. The fourth patient, a 48-year-old woman, had a micropapillary carcinoma within a hyalinizing trabecular adenoma. She is also free of disease 5 years following excision of the involved lobe. These findings suggest that hyalinizing trabecular thyroid tumors have a malignant counterpart, similar to conventional follicular adenomas, and that papillary thyroid carcinomas may arise within hyalinizing trabecular thyroid tumors.