Malignant peripheral nerve sheath tumour in the ischio-rectal fossa.

Primary sarcomas in the ischiorectal fossa are occasionally reported and represent a significant challenge due to the proximity of rectum, levator muscles and pudendal neurovascular structures. We report a case in which the diagnosis changed between biopsy (desmoid tumour) and resection (malignant peripheral nerve sheath tumour), requiring a multidisciplinary surgical approach involving different sub-specialties. It also illustrates the importance of undertaking sarcoma surgery in a recognized sarcoma centre with sarcoma expertise available across a range of disciplines.

A rare case of low-grade endometrial stromal sarcoma with myxoid differentiation and atypical bizarre cells.

Endometrial stromal sarcoma (ESS) is a rare mesenchymal tumor with characteristic histological appearances, consisting of diffuse infiltrate of small uniform endometrial stromal cells with a multinodular arrangement and distinct vascular pattern. Less common variants of ESS include "mixed endometrial stromal and smooth muscle tumors", "endometrial stromal tumors resembling ovarian sex cord tumors" and "endometrial stromal neoplasms with endometrial glands", and "aggressive endometriosis". Rarely do endometrial stromal tumors have a prominent fibrous or myxoid appearance which causes confusion and possible misdiagnosis as myxoid leiomyosarcoma. In this report we present a very unusual subtype of ESS in a 32-year-old woman. The tumor revealed atypical pleomorphic bizarre cells which were stained positive only with vimentin and CD10 in an abundant myxoid matrix. A low-proliferative rate was established with MIB-1 staining. To our knowledge such appearance has not been previously reported.

Malignant mixed mesodermal tumours: biology and clinical aspects.

Mixed mesodermal tumours (MMTs) are relatively rare gynaecological tumours that have been poorly studied in clinical and molecular terms. They are chemosensitive (at least initially), although ultimately they have a poor prognosis. The biology of the tumour is fascinating in view of its composition of both epithelial and mesenchymal entities. We review herein the literature on the clinical and biological aspects of this malignancy.

Neuron-specific enolase and its mRNA are highly expressed in large congenital nevi: a study using immunocytochemistry, biochemical assay, and in situ hybridization.

The malignant transformation of congenital nevocellular nevi, both large and small, is controversial and presents problems in management. The size of the lesion is taken to indicate potential malignant transformation, but this is an arbitrary scale. A more reliable biological indicator is needed to help predict the lesions at risk. Following the localization of neuron-specific enolase to most cells of the diffuse neuroendocrine system and their neoplasms (including benign and malignant melanocytic lesions), it has been suggested that its level is related to tumor activity. In a prospective trial, the presence of neuron-specific enolase immunoreactivity, its concentration, and gene expression in nevus cells were studied in 31 congenital melanocytic nevi of various sizes (1.5 cm to bathing trunk) using immunocytochemistry, biochemical assay, and in situ hybridization. Twenty-five of the 31 congenital nevi were immunoreeactive to neuron-specific enolase antiserum, with stronger immunostaining in the larger lesions. There is an apparent linear relationship between the size of the nevi and the level of neuron-specific enolase (expressed as nanograms per milligram protein). Neuron-specific enolase mRNA was highly expressed in most of the large congenital nevi (greater than 15 cm in diameter), as revealed by autoradiography following in situ hybridization. Our results show that neuron-specific enolase and its mRNA are expressed to a greater extent in large congenital nevi compared with the smaller lesions. This might prove to be a useful indicator of those lesions at risk of malignant transformation.

Relation of cervical glandular intraepithelial neoplasia to microinvasive and invasive adenocarcinoma of the uterine cervix: a study of 121 cases.

AIMS: To examine the relation between invasive adenocarcinoma and its alleged precursor, cervical glandular intraepithelial neoplasia (CGIN), and to assess the management and outcome of CGIN and the validity of using the term "microinvasive adenocarcinoma." METHODS: The clinical and pathological features of 121 cases of glandular neoplasia of the cervix diagnosed between the years 1990 to 1995 were examined for the following: histological diagnosis, smear records, type of treatment, the association between the precursor lesions and invasive disease, and follow up. RESULTS: 27 cases were identified as low grade CGIN (L-CGIN) and 38 as high grade CGIN (H-CGIN), 10 as microinvasive adenocarcinoma (less than 5 mm in depth), and 46 as invasive adenocarcinoma. The ratio of non-invasive to invasive disease was 1.12:1. The mean age of women was 39, 43, 43, and 48 years for L-CGIN, H-CGIN, microinvasive, and invasive adenocarcinoma, respectively. L-CGIN was seen in 13% and 18% of H-CGIN and microinvasive disease, respectively. H-CGIN was seen in 100% of microinvasive and 26% of invasive adenocarcinomas. The available smears before diagnosis predicted 59% of L-CGIN, 70% of H-CIGN, 100% of microinvasive adenocarcinoma, and 32% of invasive adenocarcinomas. Treatment of 74% of L-CGIN, 52% of H-CIGN, and 10% of microinvasive adenocarcinoma was by diathermy loop excision only. The remaining cases had hysterectomy. Residual disease was found in 43%, 50%, and 33% of hysterectomies for L-CGIN, H-CGIN, and microinvasive adenocarcinoma, respectively. This is correlated with positive margins, or disease within 3 mm of margins on loop specimens. Cervical smear follow up for two to seven years revealed no recurrence of glandular lesions in any of the cases of CGIN or microinvasive adenocarcinoma. CONCLUSIONS: Precursor glandular lesions tend to progress to invasive carcinoma. There is a progressive increase in age of patients from L-CGIN to invasive disease, a span of approximately 10 years. There is a high association between H-CGIN and invasive disease. In the management of such alleged precursors, it is important to ensure adequate free margins of at least 3 mm. Microinvasive adenocarcinoma appears to have an excellent prognosis if treated by hysterectomy.

Histological features of CIN3 and their value in predicting invasive microinvasive squamous carcinoma.

AIMS: To determine the histological features in CIN3 associated with or predictive of subsequent microinvasion. METHODS: The histological appearances of CIN3 accompanying 120 cases of microinvasive carcinoma of the uterine cervix were retrospectively studied. Major features were defined as those present in greater than 80% of cases of microinvasive carcinoma (MICA) and less than 10% of control cases of CIN3. One hundred cases of CIN3, 36 showing all, and 64 lacking all, of the major features associated with microinvasion, as defined in the retrospective study, were prospectively studied. Deeper levels were cut to exclude the presence of microinvasion in the original biopsy specimen and negative cases were followed up for a period of up to 18 months in order to assess rates of recurrence or progression. RESULTS: The major features identified in CIN3 associated with microinvasive carcinoma were extensive involvement of surface epithelium and deep endocervical crypts by expansile CIN3, luminal necrosis, and intraepithelial squamous maturation. Other features more commonly present in MICA associated CIN3 than in controls included frequent mitosis and apoptosis, pericryptal concentric fibroplasia, pericryptal inflammatory infiltrate, pronounced cellular pleomorphism, nuclear changes (distinct nucleoli and chromatin clearing), and the emergence of streams of darkly stained spindle cells oriented at right angles to the basement membrane. In the prospective study 83% of cases illustrating the major MICA associated features revealed evidence of MICA or frank invasion either on serial sections of the original biopsy or on subsequent biopsy. None of the 64 cases of CIN3 that lacked these features showed evidence of invasion on serial sections or on further follow up over 18 months. CONCLUSIONS: The data strongly suggest that cases of CIN3 which have a higher probability of association with or rapid progression to invasive disease can be identified. When these features are present in a biopsy specimen of CIN3, serial sections should be performed to exclude the presence of microinvasion. Closer clinical follow up of these patients may be needed.

Giant cell tumour of tendon sheath (localised nodular tenosynovitis): clinicopathological features of 71 cases.

AIMS/BACKGROUND: Giant cell tumour of the tendon sheath (GCTTS) is regarded as the most common neoplasm of the hand that can recur after excision. The objective of this study was to review a series of cases in our department and to determine any clinical or pathological features that might predict the likelihood of recurrence. METHODS: Clinical data, obtained from pathology request forms and in patient notes, along with the gross and microscopic appearances of 71 cases of GCTTS were evaluated. RESULTS: Clinical features and pathological features identified were similar to those of previous studies. In comparison with previous studies a higher mitotic count (range, 1-21 mitoses/10 high power fields (HPF); mean, 5/10 HPF) was noted in all cases, irrespective of recurrence and numerous apoptotic bodies (up to 30/10 HPF), mainly formed from osteoclast-like giant cells, were present. CONCLUSIONS: GCTTS is a relatively rare soft tissue tumour of uncertain histiogenesis. Mitotic and apoptotic figures are a common feature and do not indicate clinical behaviour. Complete local excision is the treatment of choice.

The borderline cervical smear: colposcopic and biopsy outcome.

AIMS: To review the outcome of women referred with smears showing borderline nuclear change (BNC), and to determine any differences in outcome if BNC was persistent, preceded by dyskaryosis, or followed treatment for cervical intraepithelial neoplasia (CIN). In addition, to determine criteria that might permit delineation of a BNC subtype, predictive of CIN. METHODS: The records of 178 women referred for colposcopy in 1993, with last smear showing BNC, were obtained from our laboratory database. The cytology, colposcopy, and biopsy follow up for a five year period were also obtained. The patients were divided into three categories according to their smear status before the last referral borderline smear: category 1, persistent BNC (n = 39); category 2, BNC preceded by dyskaryotic smears (n = 100); and category 3, BNC after treatment for CIN (n = 39). The referral borderline smears were reviewed on cases with negative outcome and those with a biopsy diagnosis of CIN2 and CIN3. RESULTS: In 50 women (28%) no biopsy was deemed necessary after colposcopic assessment. The biopsy results in the remaining 128 (72%) women were as follows: normal in 18 (10%), koilocytosis in 12 (7%), CIN1 in 45 (25%), CIN2 in 32 (18%), and CIN3 in 21 (12%) women. High grade lesions (CIN2, CIN3) were seen on biopsy in 14 of 39, 33 of 100, and six of 39 cases in category 1, category 2, and category 3, respectively. Blind review of the referral borderline smears from 53 women with a biopsy diagnosis of high grade lesions (32 CIN2, 21 CIN3) confirmed they were borderline in 23, upgraded them to mild dyskaryosis in 15, and found that 14 cases of isolated moderate or severe dyskaryotic cells had been missed originally. The borderline change was in mature squamous cells in five of 23 and in immature metaplastic epithelium in 18 of 23 cases. After smear review in 68 women with negative outcome, 36 smears were reclassified as negative in keeping with inflammation and atrophy, three were considered unsatisfactory, one was upgraded to CIN1, and 28 were confirmed as BNC. Of the latter, 25 of 28 were in mature squamous cells. The five year follow up on women with negative colposcopy (n = 50), negative loop excision of transformation zone (LETZ) (n = 18), and LETZ with koilocytosis (n = 12) showed subsequent high grade CIN on LETZ in 16, 0, and two patients, respectively. CONCLUSIONS: On referral of women for colposcopy with last smear showing BNC, the outcome was high grade CIN in over 30% of cases, irrespective of whether the borderline smear was preceded by another borderline smear or by a dyskaryotic smear. In contrast, in those referred because of BNC after treatment of CIN, high grade CIN was seen less frequently (15% of cases). Furthermore, in cases that necessitated loop excisions, high grade CIN was seen in 41%. This study also showed that BNC associated with inflammation or atrophy, or BNC in mature squamous cells, appears to have lower predictive value for CIN than those cases where BNC is associated with immature metaplastic epithelium. The use of terms such as "BNC favour reactive" for the former and "BNC favour dyskaryosis" for the latter is recommended, together with follow up by cytology and colposcopy, respectively.

Effect of using templates on the information included in histopathology reports on specimens of uterine cervix taken by loop excision of the transformation zone.

AIM: To determine the change in information relayed from histopathologists to clinicians by using templates for reporting specimens of uterine cervix sampled by loop excision of the transformation zone (LETZ). METHODS: Minimum datasets for the information required from LETZ specimens received from the colposcopy clinic, Royal Infirmary, Edinburgh, were incorporated into templates on the clinical service computer (Pinnacle) of the pathology department, University of Edinburgh. Pathologists completed hard copy versions, which were transcribed into the computer templates for report generation. The effect of the changes on the quality of the pathology reports was studied. The number of cases in which each item in the dataset received comment in template generated reports was compared with that in traditional prose reports compiled before the use of the templates and in prose reports issued after the introduction of the templates. Questionnaire studies were undertaken of clinicians' and pathologists' opinions of the template reports. RESULTS: In the template reports nearly all items received comment in almost 100% of cases. In the prose reports issued both before and after the templates were in use, most items were mentioned in a significantly lower proportion of cases. Clinicians thought the template reports were clearer and the information could be more readily assimilated than from the prose versions. CONCLUSIONS: The use of template reports in these types of specimen allowed more consistent and detailed information transfer. The change appeared to result from the use of the templates rather than from increased awareness of the items to be reported.

Squamous carcinoma of the uterine cervix with CIN 3-like growth pattern: An under-diagnosed lesion.

Invasive squamous carcinomas of the cervix have traditionally been classified into keratinizing, non-keratinizing, verrucous, warty (condylomatous), papillary transitional (squamo-transitional), and lymphoepithelioma-like carcinomas. The majority of these tumors are easily recognized. We present for the first time the pathological appearances of six cases of invasive squamous carcinoma with growth pattern simulating tangentially cut CIN 3 involving endocervical glandular crypts/clefts. In all cases initial diagnosis on biopsy and/or loop excision was thought to be CIN 3, perhaps with suspicion of early invasion. On further excision and/or on clinical grounds the tumors were frankly invasive. We propose the use of the term squamous carcinoma with "CIN 3-like growth pattern" for such lesions. This is in order to avoid misinterpretation as CIN 3 with subsequent inappropriate management of patients with this type of tumor.

Fibrosarcoma arising in an ovarian mucinous tumor: a case report.

A case of an ovarian mucinous tumor with a mural nodule is reported. The mucinous tumor was solid and cystic and contained benign, borderline and malignant elements. Within the solid area a nodule representing fibrosarcoma was identified. Mucocoele of the appendix was the other finding in this case. To the best of our knowledge this is the first description of fibrosarcoma arising in an ovarian cystadenocarcinoma.

Accuracy of cervical smears in predicting the grades of cervical intraepithelial neoplasia.

This is a retrospective study carried out to assess the correlation between the cytology and histology of cervical intraepithelial neoplasia in 1325 women. A poor correlation between the cytologic and histologic diagnosis of the various grades of CIN was shown. Forty-one percent of smears with repeated borderline change and 50% of those predicting CIN1 showed a higher grade of CIN on histology. The overall apparent false negative rate of cervical smears for high grade CIN (CIN2 and CIN3) was 19% and for CIN3 alone was only 3%. It is therefore concluded that there is a consistent tendency for cervical cytology to underestimate the severity of histologic lesions and it is therefore important that the clinicians ensure adequate follow-up of patients whose smears show a lesser degree of abnormality.

The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in the uterine cervix and cervical squamous neoplasia.

This is a retrospective study, in which PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA) was used in the assessment of 20 cases of FIGO stage IB cervical carcinoma, 30 cases of CIN, 10 cases of koilocytosis and 20 cases in which the transformation zone was histologically normal. The results showed that in the normal transformation zone the proliferative compartment was confined to the first 1-2 suprabasal cell layers. In CIN the pattern of staining corresponded to the grade of the lesion. In viral wart lesions occasional koilocytes demonstrated strong nuclear staining. In all cases of stage IB cervical carcinoma the PC10 index was high, irrespective of tumor grade response to treatment.

Uterine carcinosarcomas in patients receiving tamoxifen. A report of 19 cases.

Uterine carcinosarcomas are highly aggressive neoplasms with a tendency to early extrauterine spread, high stage at diagnosis, and a poor prognosis. Tamoxifen is widely used as adjuvant therapy in the treatment of breast cancer and is known to cause endometrial proliferative lesions, including adenocarcinoma. In recent years, there have been occasional reports of uterine carcinosarcoma in patients taking tamoxifen. The aim of this study is to describe the clinicopathologic profile in 19 women taking tamoxifen who subsequently developed uterine carcinosarcoma. Nineteen patients were identified from cases of uterine carcinosarcoma diagnosed at three institutions. The case notes were examined and the pathology reviewed. The age at diagnosis of carcinosarcoma ranged from 47 to 91 years (mean 71 years). All patients were postmenopausal and received 20 mg tamoxifen daily; the duration of treatment ranged from 1 to 15 years (mean 7.1 years). The cumulative dose of tamoxifen ranged from 7.3 to 109.5 g. Ten tumors were stage I, one stage II, seven stage III, and one stage IV. Ten of the carcinosarcomas were homologous, and nine contained heterologous elements in the form of rhabdomyoblasts (six cases) or malignant cartilage (three cases). The overall prognosis was extremely poor. Fifteen patients died within 35 months of the diagnosis of carcinosarcoma (mean 12 months). Two patients are alive with very short follow-up periods, and two were lost to follow-up. The reported data support an association between tamoxifen therapy and the development of uterine carcinosarcoma. The risk is likely to be highest in those patients who have been taking tamoxifen for a prolonged period. A majority of tumors in the present study were stage I, and this suggests that uterine carcinosarcomas in patients taking tamoxifen may be diagnosed at an earlier stage than those arising de novo. However, the prognosis was still poor even with low-stage disease. Properly controlled epidemiological studies are necessary to confirm an association between tamoxifen and uterine carcinosarcoma.

Cutaneous malignant melanoma in children and adolescents in Scotland, 1979-1991.

All cases of cutaneous malignant melanoma in Scotland have been registered by the Scottish Melanoma Group since 1979, and there are currently more than 4700 cases on the registry. Of these, only 50 cases are in patients 18 years of age and younger (1.04 percent of all melanomas); 15 of these were prepubertal, i.e., 14 years or younger (0.3 percent of all melanomas). The nine cases of documented metastases occurred in children with tumor thickness of 1.50 mm or more, with only one of these metastases occurring in a prepubertal child. Eight of these patients with metastatic disease died, with a maximum survival of 4 years. A reliable clinical history was obtained from the families of 23 patients. Eight of them had a history of preexisting congenital nevocellular nevus. In this series, no case arose in a large congenital nevocellular nevus. Histological review showed that the majority of cases (58 percent) exhibited typical cytological and architectural features of malignant melanoma. In the remaining cases, the lesions were difficult to fit into any of the classic patterns of malignant melanoma or of the known benign nevocellular lesions.

Papillary squamotransitional cell carcinoma of the uterine cervix: an advanced stage disease despite superficial location: report of two cases and review of the literature.

Papillary carcinoma of the uterine cervix with features reminiscent of transitional cell carcinoma of urothelial origin is a poorly recognized subtype of cervical carcinoma. This tumour has a propensity for late metastasis and local recurrence in spite of the fact that histologically it could be misinterpreted as cervical intraepithelial neoplasia grade 3 (CIN3) with a papillary configuration or as a squamous papilloma. In this report we describe two examples of papillary squamous/transitional carcinoma of the cervix with literature review. The results indicate that this tumour occurs mainly in postmenopausal women, is potentially aggressive and presents at a more advanced stage inspite of the histological appearance suggesting a superficial or early invasive lesion.

Primary extra-cranial meningioma following total hip replacement.

A 61-year-old man presented with pain at the left hip and decreased mobility 10 years after total hip replacement. Imaging demonstrated a large destructive expansile mass adjacent to the prosthesis. Histological analysis confirmed the presence of an extra-cranial meningioma. Primary tumours after total hip replacement are rare and include soft tissue sarcomas, bone sarcomas and lymphomas. To our knowledge, no previous cases of primary extracranial meningioma have been identified. The imaging features, histology, pathogenesis and differential diagnosis are discussed.