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PubMed2003

Multilocular prostatic cystadenoma with high-grade prostatic intraepithelial neoplasia.

Multilocular prostatic cystadenoma is a rarely encountered neoplasm located in the midline between the bladder and rectum that is either attached to the prostate by a pedicle or separate from the prostate entirely. Histologically and immunohistochemically these lesions resemble benign prostate tissue. We report the first case of this entity for which multifocal high-grade prostatic intraepithelial neoplasia (PIN) is identified. Conceptually, the finding of high-grade PIN in multilocular prostatic cystadenomas provides further evidence that these lesions are fully analogous to the prostate gland not only in their morphology and immunohistochemistry but also in their predilection for the same diseases.

Cystadenoma↗

PubMed1995

Pineal region tumours treated with interstitial brachytherapy with low activity sources (192-iridium).

Three patients with tumours of the pineal region underwent interstitial Ir-192 brachytherapy. Histological diagnoses were obtained in all patients, by stereotactic biopsy and included one germinoma, one mixed pineoblastoma/pineocytoma, and one astrocytoma grade III. Our approach to pineal region neoplasms is first to decide whether stereotactic biopsy or surgery should be performed. When a pineal lesion is thought to be benign on the basis of imaging, such as benign teratoma, surgery is performed to resect the entire lesion. When a definitive diagnosis is not possible, stereotactic biopsy is performed to obtain a histological diagnosis for treatment planning, using a Brown-Roberts-Wells (BRW) stereotactic apparatus with computed tomography (CT) or magnetic resonance imaging (MRI). When a lesion is malignant and localized, stereotactic implantation of catheters for interstitial brachytherapy is performed simultaneously. Radioactive Ir-192 seeds are inserted into the catheters and maintained for 5-10 days to give 36 Gy of irradiation at the tumour periphery. Sequential CT scans and MRI after treatment revealed tumour disappearance in two patients with germinoma and high grade astrocytoma and tumour reduction in the patient with mixed pineoblastoma/pineocytoma. No significant morbidity or mortality occurred in any of these patients after stereotactic biopsy and brachytherapy. The technique and the advantages of this therapeutic approach to selected pineal region tumours are described and discussed.

Adult↗

PubMed1975

Spindle cell carcinoma of the larynx.

A clinicopathologic correlation of 39 cases of a histologically biphasic malignant neoplasm of the larynx is presented. The histologic pattern of this entity was mainly that of a malignant spindle cell process, but a definite squamous cell carcinoma component was evident. Grossly the tumors were usually prominently polypoid. A morphologic transition of the squamous cell carcinomatous element into the spindle cell component was strongly suggested, supporting the contention that this entity is pathogenetically a pleomorphic or spindle cell squamous cell carcinoma. Follow-up information on 20 cases indicated a two-year mortality of 40 per cent, refuting the contention that this entity is of low-grade malignancy. Complete surgical removal of the neoplasm, with or without irradiation, offered the best therapeutic approach. Irradiation alone was unsuccessful.

Aged↗

PubMed1996

Association between human papillomavirus type and clonal status of cervical squamous intraepithelial lesions.

BACKGROUND: Lesions that are histologically classified as precursors of cervical cancer, which are often referred to as squamous intraepithelial lesions (SILs), represent a heterogeneous clinical entity that can be associated with many different types of human papillomaviruses (HPVs) and have a variable biologic behavior. Approximately one half of low-grade SILs behave as non-neoplastic, productive viral lesions that frequently regress spontaneously, whereas the other half behave as neoplasms and either persist or progress to a histologically higher grade lesion. Identification of biomarkers that reliably differentiate those low-grade SILs with the properties of a non-neoplastic viral infection from those with the properties of neoplasia would provide a more rational basis for decisions about disease management. Since monoclonality is a hallmark of neoplasia irrespective or organ site, clonal status might represent one such biomarker. PURPOSE: To better understand the pathobiology of SILs, we analyzed the clonality of low-grade and high-grade SILs and compared their clonal status with their associated HPV types. METHODS: One hundred forty formalin-fixed, paraffin-embedded cervical biospy and loop electrosurgical specimens, originally diagnosed as SILs, were obtained from the pathology archives of both the Columbia-Presbyterian Medical Center and Kyto Diagnostics in New York. Clonality was determined with the use of a polymerase chain reaction (PCR) based method that detects nonrandom X-chromosome inactivation. This PCR-method amplifies a polymorphic region of the androgen receptor gene that is flanked by several differentially methylated enzyme sites. The same tissue was also analyzed for HPV DNA with the use of PCR and both L1 and E6 "consensus" primers. RESULTS: All 25 evaluable cases of high-grade SILs were determined to be monoclonal. Although 54 (68%) of 79 evaluable low-grade SILs were monoclonal, 25 (32%) of 79 low-grade SILs were polyclonal. A strong association was observed between HPV type and clonal status, with a total of 71 (47 low-grade and 24 high-grade) SILs determined to be monoclonal and containing HPV types 16, 18, 31, 33, 35, 39, 45, 56, 58, or 65. In contrast, 22 (92%) of the 24 low-grade SILs that contained another type of HPV were polyclonal (Fisher's exact test, two-sided, P</-.001). CONCLUSIONS: Our findings suggest that the histopathologic entity termed low-grade SIL consists of two different types of lesions that are biologically distinct. One lesion is monoclonal and is associated with HPV types 16, 18, 31, 33, 35, 39, 45, 56, 58, or 65. The second types of low-grade SIL is polyclonal and is associated with other types of HPV.

Alleles↗

PubMed2005

Skull metastasis from clear cell chondrosarcoma.

A 67-year-old man presented with left lower cranial nerve paresis and dysfunction of the left cerebellar hemisphere 4 years after amputation of the left lower leg because of clear cell chondrosarcoma (CCC). Neuroimaging studies showed an osteolytic extradural mass with homogeneous enhancement in the left posterior fossa. Bone scintigraphy disclosed a single high-uptake lesion at the same site. The tumor was removed totally via a left suboccipital craniotomy. Histological examination found mainly clear cells arranged in a microlobular pattern separated by thin fibrovascular stroma. The nuclei were regular with few mitotic figures. Immunohistochemical staining showed the tumor cells reacted intensely for both S-100 protein and vimentin. Osteoclast-like multinucleated giant cells were found at the periphery of the lobules. The primary tumor showed the same findings and the metastatic tumor manifested no malignant change. The histological diagnosis was metastatic CCC. CCC is a very rare neoplasm with slow growth and low-grade malignancy. Distant metastasis is rare but can occur in the skull base bone despite radical resection of the primary tumor. Osteolytic findings of homogeneous enhancement on magnetic resonance imaging and a high uptake on bone scintigraphy are indicative of metastatic tumor from previous CCC.

Aged↗

PubMed2006

Cytokeratin 15 expression in neoplasms with sebaceous differentiation.

BACKGROUND: Recent studies have demonstrated that the cytokeratin 15 (CK15)-positive stem cells located in the hair follicle bulge are also involved in sebaceous gland renewal. No previous studies have dealt with the CK15 expression in sebaceous neoplasms. METHODS: We studied the CK15 expression in 30 sebaceous neoplasms including 10 sebaceomas (sebaceoma defined as a distinct benign neoplasm with sebaceous differentiation), 10 sebaceous neoplasms of Muir-Torre syndrome, and 10 sebaceous carcinomas, in addition to that in the mantles of normal hair follicles. RESULTS: CK15 was positive in the undifferentiated sebocytes of the mantles. All 10 sebaceomas showed CK15 expression in the basaloid, germinative cells. Both sebaceous neoplasms in Muir-Torre syndrome and sebaceous carcinomas demonstrated negative or only a focal positive reaction, including the occasional aberrant expression in matured sebocytes, to CK15. CONCLUSIONS: CK15 may be a useful marker for stem cells with a sebaceous fate, and a constant CK15 expression in sebaceomas supported the hypothesis that sebaceoma is a benign neoplasm of sebaceous germinative cells in the mantles. The similar staining pattern of CK15 between sebaceous neoplasms in Muir-Torre syndrome and sebaceous carcinomas may be one piece of evidence supporting the hypothesis that most sebaceous neoplasms in Muir-Torre syndrome are low-grade sebaceous carcinomas.

Adenocarcinoma, Sebaceous↗

PubMed2001

[Histopathological diagnosis of primary liver tumors].

Although modern imaging can predict the diagnosis of the vast majority of liver neoplasms, liver biopsy remains the safest, most accurate and most economical diagnostic gold standard for therapeutic implications. Refined preparation techniques using fine-needle biopsy lead to the correct diagnosis by conventional staining in most cases. Metastases and rare mesenchymal liver tumors that mimic primary hepatocellular tumors morphologically can be distinguished by use of a panel of antibodies in immunohistochemistry. Precursors of hepatocellular carcinoma (HCC) remain difficult to categorize in small biopsy specimens. Differentiation of HCC from regenerative nodules and liver cell adenomas can be achieved by molecular techniques applicable to formalin-fixed and paraffin-embedded tissue (FISH or ISH). The grading and staging of resected malignant liver neoplasms according the pTNM system still have the most important prognostic impact, but screening of changes in the cell cycle by immunohistochemistry and application of molecular techniques may prove to have prognostic value in the near future.

Biopsy↗

PubMed1993

The effect of immunosuppression on pre-existing cancers.

This study of 939 pre-existing malignancies that occurred in 913 renal transplant recipients showed that in 823 patients the tumors were treated prior to or at transplantation, in 78 after transplantation, at an unspecified time in 20, while 18 received no treatment. Of patients treated pretransplantation 185 (22%) developed recurrences posttransplantation. Low recurrence rates (0-10%) occurred with incidentally discovered renal tumors; lymphomas; and testicular, uterine cervical, and thyroid carcinomas. Intermediate recurrence rates (11-25%) occurred with carcinomas of the uterine body; Wilms' tumors; and carcinomas of the colon, prostate, and breast. High recurrence rates (> or = 26%) occurred with carcinomas of the bladder, sarcomas, malignant melanomas, symptomatic renal carcinomas, nonmelanomatous skin cancers, and myelomas. Overall 53% of 185 recurrences occurred in patients treated 0-24 months pretransplantation, 34% in patients treated 25-60 months pretransplantation, and 13% in patients treated > 60 months pretransplantation. Of 78 patients whose cancers were first treated after transplantation, 27% developed recurrences. However, 63% did not do so in follow-ups averaging 53 months. A two-year waiting period between treatment of cancer and transplantation is justified for most neoplasms except for incidentally discovered renal carcinomas, in situ carcinomas, and possibly focal neoplasms (a small single focus), low-grade bladder cancers, and basal cell skin cancers. In these cases no waiting period is necessary. On the other hand, a waiting period > 2 years is necessary for most malignant melanomas, breast carcinomas, and colorectal carcinomas. Conflicting data are presented as to whether immunosuppression affects growth of existing tumor cells but most of the evidence suggests acceleration of neoplastic growth.

Adult↗

PubMedDate not supplied

Progesterone receptors are expressed with higher frequency by optic nerve sheath meningiomas.

Optic nerve sheath meningiomas are infrequent neuropathological specimens as conservative management of these benign tumors is often adopted. It is established that progesterone receptor expression in meningiomas may be of functional significance in the growth of these neoplasms and is related to the tumor grade and likelihood of recurrence. In addition, progesterone receptor expression can be indicative of a potential response of surgically less accessible meningiomas to hormonal treatments. We analyzed 30 surgically resected optic nerve sheath meningiomas and showed high levels of progesterone receptor expression compared to benign meningiomas from other intracranial sites suggesting these tumors may be amenable to hormonal therapy.

Adult↗

PubMed1975

Radiology and fine needle aspiration biopsy in the diagnosis of tumours of the kidney.

The value of angiography and fine needle aspiration biopsy in detecting, grading and staging of renal tumours was studied in 55 patients with renal tumours suspected clinically or on urography. 42 patients had malignant tumours. A correct angiographic diagnosis was made in 94% of the renal adenocarcinomas, the corresponding percentage for the aspiration biopsies was 71%. A combination of angiography and cytologic examination gave the correct diagnosis in 97%. In 4 cases of renal pelvic carcinoma the angiography showed extensive hydronephrosis only, the final diagnosis in these was cases achieved by fine needle aspiration biopsy. Angiographic staging of 30 renal adenocarcinomas was made according to the TNM system. The radiological staging was correct in 30% of T3 tumours, but in only 50% of T1 tumours and in one out of five T2 tumours. The difficulties seemed to be in determining the relation of tumours situated marginally near the renal capsule. Angiographic grading of the tumour was made according to the vascular pattern and the time of venous filling. Sparse vascularity and venous filling time of over 5 seconds was found in highly differentiated carcinomas and abundant vascularity and fast venous filling in neoplasms of moderate or low differentiation. The cytologic grading correlated fairly well with the histological grading. This study shows that angiography combine with fine needle aspiration biopsy provides good facilities for obtaining a correct diagnosis in renal tumours and preoperative information of the extent and degree of differentiation of renal malignant tumours.

Adenocarcinoma↗

PubMed1999

Papillary urothelial neoplasms of low malignant potential. Clinical and biologic implications.

BACKGROUND: Knowledge of the long term outcomes of patients with papillary urothelial neoplasms of low malignant potential (LMP) is limited. METHODS: The authors studied 112 consecutive patients who were diagnosed with papillary urothelial neoplasms of LMP (formerly Ta, World Health Organization Grade 1 of 3 papillary urothelial carcinoma) at the Mayo Clinic between 1958 and 1963. All histologic slides were reviewed and fulfilled the diagnostic criteria of the 1998 World Health Organization/International Society of Urological Pathology classification system. RESULTS: Patient age at diagnosis ranged from 33 to 99 years (mean, 65 years). The male-to-female ratio was 3:1. The mean follow-up was 12.8 years (range, 0.1-35 years; median, 11.7 years). Twelve patients had biopsy-proven, noninvasive urothelial carcinoma; 17 patients had cystoscopically detected recurrences (all were treated by fulguration without biopsy); and 4 patients developed invasive urothelial carcinoma (including 2 with muscle-invasive carcinoma). Twelve (75%) of 16 patients with biopsy-proven recurrence or progression had cancer dedifferentiation, which resulted in a diagnosis of higher grade cancer than was indicated on initial biopsies. The mean interval from initial diagnosis to development of invasive carcinoma was 13.3 years (range, 10-14 years). Three patients died of bladder cancer. CONCLUSIONS: Patients with papillary urothelial neoplasms of LMP have increased risks of local recurrence, progression, and death from bladder carcinoma. Long term clinical follow-up may be indicated for patient management.

Adult↗

PubMedDate not supplied

[Determination of grade of urothelial carcinoma according to WHO 2004 classification].

Several classifications of transitional/urothelial cell tumors have been proposed during last few years in order to standardize nomenclature, and criteria for grading and invasion. They also aimed to avoid the term cancer for neoplasms that very rarely invade, recur, and/or cause death of the patient. As a result of these efforts a new WHO classification emerged in the year 2004. Instead of the term transitional, the use of urothelial neoplasms was recommended. In the group of noninvasive urothelial neoplasms, a new category of tumor of low malignant potential was added. Three-tier grading of papillary noninvasive tumor was substituted by low and high-grade category. Criteria for the grades are cited in the classification but are somewhat imprecise and difficult to apply. On the basis of the data from the literature and our own experience, in the transitional period we recommend the use of WHO 1973 simultaneously with the new one. Problems of the identification of lamina propria invasion are still not solved, and therefore the use of additional histochemical and immunohistochemical methods should be recommended in difficult cases.

Carcinoma, Transitional Cell↗

PubMed2006

RhoA protein expression correlates positively with degree of malignancy in astrocytomas.

Astrocytic tumors are the most common intracranial neoplasms. Their prognoses correlate with a conventional morphological grading system that suffers from diagnostic subjectivity and hence, inter-observer inconsistency. A molecular marker that provides an objective reference for classification and prognostication of astrocytic tumors would be useful in diagnostic pathology. RhoA, a GTPase protein involved in cell migration and adhesion, has been shown to be upregulated in a variety of human cancers. Based on direct analysis of clinical materials, our study demonstrates increased expression of RhoA in high-grade astrocytomas. This observation may be relevant to astrocytoma biology and the development of potential therapeutics against high-grade astrocytomas. Of more immediate consequence, utilization of this marker may aid in the routine pathological grading (and hence prognostication) of astrocytomas.

Adolescent↗

PubMed1979

An immunohistochemical study of distribution of carcinoembryonic antigen in epithelial tumours of the ovary.

An immunohistochemical study of the tissue CEA content of 82 epithelial neoplasms of the ovary has shown that mucinous tumours contain more of this substance than do their serous counterparts; otherwise a knowledge of tissue CEA content appears to be of little value in the differential histological diagnosis of this group of neoplasms. Among mucinous tumours there is only a partial correspondence between their degree of malignancy, as assessed histologically, and their content of CEA. It is postulated that immunohistological study of tissue CEA may add a degree of finesse to morphological analysis of these neoplasms and thus allow for a more precise grading of their degree of malignancy.

Adenocarcinoma↗

PubMed1999

Urothelial papilloma of the bladder. Clinical and biologic implications.

BACKGROUND: An international consensus has been reached regarding diagnostic criteria for papilloma of the urinary bladder. However, the incidences of recurrence and progression in patients with urothelial papilloma are uncertain. METHODS: The population for this study consisted of 52 patients who were diagnosed with urothelial papilloma of the bladder at the Mayo Clinic between 1914 and 1998. All histologic slides were reviewed and fulfilled the diagnostic criteria of urothelial papilloma from the 1998 World Health Organization/International Society of Urological Pathology classification system. No patients had previous or coexistent urothelial carcinoma, and none were treated after biopsy. RESULTS: The mean patient age at diagnosis was 57 years (range, 22-89 years). The male-to-female ratio was 1.9:1. The mean follow-up was 9.8 years (range, 0.1-58 years). Four patients developed recurrent papilloma (mean interval from diagnosis to recurrence, 3.3 years); 1 other patient developed papillary neoplasm of low malignant potential (Ta WHO Grade 1 papillary urothelial carcinoma) 6 years after the initial diagnosis of papilloma. None of these patients developed dysplasia, carcinoma in situ, or invasive urothelial carcinoma or died of bladder cancer. CONCLUSIONS: Patients with urothelial papilloma have a low incidence of recurrence and rarely, if ever, develop urothelial carcinoma.

Adult↗

PubMed2005

Current issues in the pathology of ovarian cancer.

The majority of primary ovarian tumors are histologically classified as surface epithelial-stromal neoplasms. The malignant potential of such neoplasms may be categorized, on the basis of the extent of epithelial proliferation and stromal invasion, as benign, borderline or malignant. Recent efforts to further classify the malignant potential of such neoplasms have produced a new system for the histologic grading of ovarian carcinoma as well as new potential histologic predictors of behavior, including micropapillary morphology and stromal microinvasion in serous tumors. Among mucinous ovarian neoplasms, new criteria have been proposed to distinguish primary ovarian from metastatic carcinomas; the distinction may be difficult but has great clinical significance. The origin of ovarian mucinous tumors associated with pseudomyxoma peritonei has been reassessed. Finally, recent pathologic findings from prophylactic salpingo-oophorectomy specimens in patients with hereditary risks for ovarian carcinoma have highlighted the additional risk for fallopian tube carcinoma and primary peritoneal carcinoma. Special processing of the pathologic specimens is required to detect early and minimal neoplasia in this setting. These current issues in the pathology of ovarian carcinoma and their clinical significance form the basis of this review.

Cystadenocarcinoma↗

PubMed2004

Pseudomyxoma peritonei and selected other aspects of the spread of appendiceal neoplasms.

The varied aspects of spread of appendiceal neoplasms are reviewed with emphasis on the often clinically dramatic phenomenon known as pseudomyxoma peritonei, a term mostly used to describe grossly evident mucin within the peritoneal cavity. The majority of cases of pseudomyxoma peritonei result from tumors primary in the appendix, which are usually low-grade. On microscopic examination pseudomyxoma peritonei is typically characterized by large aggregates of mucin which may be relatively acellular or cellular containing strips of mucinous epithelium, mucinous epithelium encircling glands and cysts, or aggregates of mucinous epithelium lying within mucin pools. High-grade adenocarcinoma of the appendix may spread to the omentum and peritoneal surfaces without grossly striking mucin deposition and resemble spread of other high-grade gastrointestinal adenocarcinomas. In many cases of pseudomyxoma peritonei in females there is involvement of one, or more often, both ovaries. The size of the ovarian neoplasms characteristically dwarfs the often relatively unremarkable appearing appendix in these cases. The ovaries are typically multilocular, although one locule may dominate, and in cases in which the primary is a low-grade appendiceal mucinous neoplasm often have a "jelly-like" consistency. In cases of spread of frank adenocarcinomas the ovarian metastases typically have a more solid, albeit still somewhat gelatinous consistency. Microscopic examination of the ovaries typically shows surface involvement, a characteristic of spread to the ovaries in general, and the glands and cysts that replace most or all of the parenchyma are typically lined by tall mucin-rich cells with, in many cases, relatively bland microscopic features. In cases of frank adenocarcinoma, the tumors may mimic closely a primary mucinous adenocarcinoma of the ovary. Spread to the ovaries may also be seen in cases of frank intestinal-type adenocarcinoma primary in the appendix and the uncommon signet ring cell carcinoma of the appendix, the latter being one cause of the Krukenberg tumor. Occasional cases are reported in the literature of ovarian spread of goblet cell carcinoid tumor of the appendix, but in our opinion most of the primary tumors in those cases are better classified as adenocarcinomas, usually dominantly of signet-ring cell type, albeit sometimes with focal neuroendocrine differentiation. Other interesting aspects of spread of appendiceal neoplasms include to the lining of the uterus and the fallopian tube. In yet other cases the tumors may present clinically as incidentally discovered mucinous aggregates within hernia sac specimens or as a scrotal mass.

Appendiceal Neoplasms↗

PubMed1992

Fibrosarcoma-malignant fibrous histiocytoma of the breast. A clinicopathological study of 32 cases.

We report the clinical and pathologic features of 32 sarcomas of the breast with features spanning the spectrum of fibrosarcomas-malignant fibrous histiocytomas. Neoplasms were categorized as high- or low-grade lesions depending on a combination of the degrees of atypia and mitotic activity. The majority of high-grade lesions had marked (3+) nuclear atypia and at least five mitotic figures per 10 hpf. High-grade lesions with moderate (2+) nuclear atypia had a mitotic activity of six or more mitotic figures per 10 hpf. All low-grade lesions had five or fewer mitotic figures per 10 hpf, and none had a score of the nuclear grade times mitotic figures of more than 10. The average mitotic activity in low-grade lesions was two mitotic figures per 10 hpf; the high-grade lesions had 12 mitotic figures per 10 hpf. Sixty-nine percent of the low-grade fibrosarcomas-malignant fibrous histiocytomas showed mild (1+) cytologic atypia, and 69% of the high-grade lesions showed severe (3+) cytologic atypia. The herringbone pattern was associated with a more favorable prognosis than the malignant fibrous histiocytoma pattern. Compared to the high-grade lesions, low-grade fibrosarcomas-malignant fibrous histiocytomas were slow-growing, produced fewer recurrences, and did not metastasize. Of the 16 women with low-grade lesions, all were free of tumor at last contact, despite recurrence in more than half of the patients. In contrast, 31% of the patients with high-grade lesions died of tumor, and 13% were alive with disease. Twenty-five percent of women with high-grade lesions developed distant metastases.

Adult↗