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The World Health Organization (WHO) grading system has a low prognostic value for early-stage oral tongue squamous cell carcinoma; greater prognostic power has been shown with tumor budding analysis. In this study, we combined tumor budding analysis with histopathologic grading according to WHO 2017. In our proposal, a revised grade I tumor is defined as a "well differentiated cohesive tumor"; revised grade II as a "moderately differentiated and/or slightly dissociated tumor"; and revised grade III as a "poorly differentiated and/or dissociated tumor." We evaluated the prognostic value of this proposed grading system in a multicenter cohort of 311 cases of early oral tongue squamous cell carcinoma. The proposed grading system showed significant prognostic value in multivariable analysis for disease-specific survival with a hazard ratio of 3.86 and a 95% confidence interval of 1.36-10.9 (P=0.001). For disease-free survival, the proposed grading system showed good predictive power in multivariable analysis (hazard ratio, 2.07; 95% confidence interval, 1.00-4.27; P=0.009). The conventional WHO grading system showed a low prognostic value for disease-specific survival and disease-free survival (P>0.05). In conclusion, the prognostic power of the WHO histopathologic grading improved significantly with incorporation of tumor budding. Our proposed grading system can be easily included in pathology reports.

Multiple self-healing squamous epithelioma (MSSE, Ferguson-Smith disease) and Loeys-Dietz syndrome (LDS) are allelic conditions associated with pathogenic variants in the transforming growth factor beta receptor 1 gene (TGFBR1). We describe a patient with a novel missense variant in this gene: c.664G > A, p.[Gly222Arg], who clinically presents with both syndromes. The patient also has a history of gastric antral vascular ectasia, which has not been reported previously in LDS.

Rationale: Primary renal carcinoid tumors are very rare and only about 100 cases have been reported in the medical literature. There are even fewer articles on the imaging manifestations of primary renal carcinoid tumors. Patient concerns: We present 3 cases of patients with lumbago and hematuria. These were cases of primary renal carcinoid tumors with initial suspicion of suprarenal epithelioma. Diagnoses: Renal lesions were detected on abdomen computed tomography (CT) imaging. The 3 cases presented as solid/cystic solid renal mass with uniform or non-uniform density, calcification in the mass, and enhanced heterogeneity. Interventions: The laparoscopic partial/radical nephrectomy were performed. Outcomes: The postoperative histological diagnosis were primary renal carcinoid tumors. Case 2 been lost to follow-up in 3 patients, and the other 2 patients (Case 1 and 3) are still alive. Case 1 had intrahepatic metastases. Lessons: Primary renal carcinoid tumors mostly present as solid mass/cystic solid mass with calcification and delayed enhancement of heterogeneity on CT imaging, but the diagnosis depends on pathological diagnosis. Hence, raising awareness of the CT features of the rare tumor in the kidney may broaden the knowledge base of radiologists.

Pilomatricoma, also known as calcifying epithelioma of Malherbe, is a common benign skin adnexal tumor with differentiation toward hair cortex cells, commonly seen in head and neck region of children. It is usually solitary. Herein, we present a rare case of pilomatricoma with extensive osseous metaplasia as a thigh swelling in an adult female, considered clinically to be a sebaceous cyst. Florid osseous metaplasia is extremely rare in cases of pilomatricoma. To date, fewer than 10 cases of pilomatricoma with extensive osseous metaplasia at different sites have been reported in the English literature.

To describe the radiological characteristics of pilomatricomas on multi-detector computed tomography (MDCT) and magnetic resonance imaging (MRI), and to correlate the radiological findings and pathological features.The radiological findings of 41 pilomatricomas in 31 patients were retrospectively reviewed. The images were evaluated with emphasis on calcifications, reticular and ring-like appearances, enhancement patterns, circular target sign and peritumoral fat stranding, and correlating these with pathological features.Of the 31 lesions evaluated by MDCT, 25(80.6%) showed different patterns of calcifications which included single in 12(38.7%) lesions and multiple in 13(41.9%) lesions, but peritumoral fat stranding was observed only in 2(6.5%) lesions. MRI scans were performed in 11 patients with 21 lesions, homogeneous and inhomogeneous hypointensities on T1-weighted (T1W) images were showed respectively in 14(66.7%) and 7(33.3%) lesions. On fat-suppressed (FS) T2-weighted (T2W) images, a ring-like hyperintensity was observed in all 21(100%) lesions, reticular hyperintensity, circular target sign, peritumoral fat stranding and secondary anetoderma were seen in 7(33.3%), 4(19%), 4(19%) and 1(4.8%) lesions, respectively; and a significant difference (P 0.05) was found when comparing the maximum diameter of tumors with (2.3 ± 1.4 mm) and without (1.1 ± 0.3 mm) reticular hyperintensity. On contrast-enhanced T1W images, all 21(100%) lesions were found to have ring-like enhancement and 7(33.3%) of them showed reticular enhancement. The reticular and ring-like appearances on MR images respectively corresponded to the pathological edematous stroma and connective tissue capsule, and the four-layer structures of the circular target sign on FS T2W images also corresponded to pathological calcifications, shadow cells, epithelial cells and connective tissue capsule, respectively.The characteristic radiological findings associated with pilomatricomas include different patterns of calcifications on MDCT images and ring-like, reticular appearances and circular target sign on MR images. Radiological findings are well correlated with pathological nature.

BACKGROUND: Dermatoscopy is a non-invasive diagnostic tool used to examine skin lesions with an optical magnification. It has been suggested as a useful tool for monitoring therapeutic response in lentigo maligna patients treated with imiquimod. OBJECTIVE: To examine the accuracy of dermatoscopy as a tool to monitor the therapeutic response of pigmented basal cell carcinoma treated with imiquimod. METHOD: The authors designed a prospective study. Patients with pigmented basal cell carcinoma were included and data regarding the dermatoscopy features were collected following the Menzies criteria, prior to initiating the imiquimod treatment. Subsequent dermatoscopic evaluations were performed at weeks 4 and 8, following imiquimod discontinuation. RESULTS: Twenty lesions were included. The most common pigmented dermatoscopy features were large blue-grey ovoid nests (80%), followed by blue-grey globules (50%) and leaf-like areas (30%). No spoke wheel areas were observed. In 17 out of 20 patients, a response was noted during the first evaluation at 4 weeks, while the clearance was noted at the second check-up after 8 weeks. In two patients, the clearance was found at the initial evaluation at 4 weeks, while in one patient, the response remained unchanged. Blue-grey globules were the fastest to exhibit clearance (50% at week 4), followed by leaf-like areas (15%) and large blue-grey ovoid nests (6.25%). CONCLUSION: According to our results, dermatoscopic evaluation enhances the accuracy in the assessment of the clinical response to imiquimod in pigmented basal cell carcinoma.

Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a benign skin neoplasm originating from hair follicle matrix cells. Pilomatrixoma is a common skin neoplasm that is often misdiagnosed as another type of skin condition. The aim of our study is to review 11 years' worth of experience in examining clinical and histopathological presentations, imaging findings, management approaches, and treatment outcomes of pilomatrixoma at a tertiary hospital. A review of the pathology database revealed that 108 extremity pilomatrixomas were excised between 2007 and 2018. Hospital charts, and pathology and orthopedic clinic records, were reviewed for patient data such as age, gender, clinical and histopathological presentations, preoperative diagnosis and imaging results, management approach, recurrence, and treatment outcomes. The main presenting symptom was a hard, subcutaneous, slowly growing mass. The preoperative diagnosis was accurate and consistent with the pathological diagnosis of pilomatrixoma in only 35 cases (32%). The optimal diagnostic tool for pilomatrixoma seems to be ultrasound imaging of superficial tissue, and the optimal first-line treatment might be surgical excision with clear margins. However, pilomatrixoma is a benign tumor, with atypical forms, and there no tumor-specific diagnostic tool is available other than careful histopathological examination.

Background Transplant patients need to be strictly followed, since the immunosuppressive therapies they usually receive can increase the risk of skin complications. This study aims to evaluate the prevalence of neoplastic skin complications in transplant patients. Methods We analyzed 256 liver or kidney transplant patients. The follow-up mean period was 7±3.5 years. It was also evaluated the prevalence of cutaneous neoplastic complications according to the immunosuppressive regimen received by patients as follows: cyclosporine, tacrolimus, steroids, mycophenolate mofetil or everolimus, in single, double or triple therapy. Results The 18.36% of patients developed neoplastic complications, among these 9.37% actinic keratoses, 8.20% non-melanoma skin cancer, and 0.78% cutaneous melanoma. Among patients who developed non melanoma skin cancer, 61.90% had basal cell carcinoma, 23.81% squamous cell carcinoma, 52% Kaposi's sarcoma and 4.76%, Malherbe's epithelioma. Conclusions This study demonstrated the increased risk of skin cancer in transplant patients during the first 7 years of follow-up and made the dermatologists aware about the need of a regular cutaneous follow-up for this subset of patients.

Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a superficial benign skin tumor that arises from hair follicle matrix cells. Although pilomatrixomas are well-recognized lesions, clinically they are frequently misdiagnosed as other skin conditions. By reviewing all the literature over the past 10 years, the aims of this article are to analyze the cause, clinical presentation, management, and outcome of pilomatrixoma among children and adults to gain a more complete understanding of this lesion in today's clinical context.A MEDLINE and EMBASE search was conducted from January 2005 to February 2015 using a combination of the terms: "child," "childhood," "adult," and keywords: "pilomatrixoma," "pilomatricoma," and "calcifying epithelioma of Malherbe." A total of 150 articles were reviewed.The lesions occurred most commonly in the first and second decades (mean age 16 years and 7 months). The commonest presentation was of an asymptomatic, firm, slowly growing, mobile nodule. Only 16% were accurately diagnosed on clinical examination. Imaging in the form of ultrasound, computed tomography, and magnetic resonance imaging has been reported. Pathological diagnosis was achieved through incision, punch, and shave biopsies. Pathological findings are discussed and summarized in this review.Pilomatrixomas are thought to arise from mutation in the Wnt pathway and has been linked to several genetic conditions. It is commonly misdiagnosed preoperatively; however, with better awareness of the lesion, it can be appropriately treated while avoiding unnecessary diagnostic tests. Complete surgical excision with clear margins is almost always curative.

Spindle cell epithelioma of the vagina is a benign entity with fewer than sixty cases described in the literature, and only two with limited imaging findings, since the early 1950s. Early pathology literature suggested the lesions were mixed tumors of myoepithelial origin, but subsequent studies have found relatively few immunohistochemical characteristics in common with other mixed cell tumors. More recently, Mullerian, urogenital sinus epithelial, and pluripotential cell origins have been proposed. Given lesion rarity and a typical lack of imaging before excision, the imaging appearance of vaginal spindle cell epitheliomas has not been fully described in the radiology literature, and without comprehensive pathology correlation. The authors describe a case of spindle cell epithelioma in a 54-year-old woman which was incidentally discovered on MRI performed for uterine fibroid embolization planning. Pathology and immunohistochemistry confirmed the diagnosis.

The so-called mixed tumors occur in a variety of sites throughout the body. While most cases are encountered in the salivary glands, several cases have been described in the female genital tract. A variety of monikers have been applied to this lesion including "spindle cell epithelioma." As in other locations, the vaginal spindle cell epithelioma (VSE) consists of a proliferation of both epithelial and mesenchymal components. Based on our extensive review of the literature, we present the 53rd reported case of VSE. More significantly, we present the most up-to-date review of this lesion, including its immunohistochemical and electron microscopic features. We also review the theories pertaining to its histogenesis incorporating current embryologic data, which together suggest a Müllerian derivation.

Lower female genital tract tumors with adenoid cystic differentiation are rare, and data on their relationship with high-risk human papillomavirus (HPV) are limited. Here we report the clinicopathologic features from a case series. Tumors with adenoid cystic differentiation, either pure or as part of a carcinoma with mixed differentiation, arising in the lower female genital tract were evaluated by means of immunohistochemical analysis for p16 expression and in situ hybridization using 1 or more probes for high-risk HPV (a high-risk probe covering multiple types, a wide-spectrum probe, and separate type-specific probes for HPV16 and HPV18) and when possible by polymerase chain reaction for high-risk HPV. Six cervical carcinomas with adenoid cystic differentiation admixed with various combinations of at least 1 other pattern of differentiation, including adenoid basal tumor (epithelioma and/or carcinoma), squamous cell carcinoma (basaloid or keratinizing), and small cell carcinoma were identified in patients ranging in age from 50 to 86 years (mean, 73 y; median, 76 y). All of these tumors were characterized by diffuse p16 expression. High-risk HPV was detected in 5 of 6 tested cases: 4 cases by in situ hybridization (all positive for HPV-wide-spectrum and HPV16) and 1 by polymerase chain reaction (HPV45). Seven pure adenoid cystic carcinomas (6 vulvar and 1 cervical) were identified in patients ranging in age from 27 to 74 years (mean, 48 y; median, 48 y). All of these tumors were characterized by variable p16 expression ranging from very limited to more extensive but never diffuse. No high-risk HPV was detected in any of these pure tumors. Lower female genital tract carcinomas with adenoid cystic differentiation appear to comprise 2 pathogenetically distinct groups. Cervical carcinomas with mixed differentiation, including adenoid cystic, adenoid basal, squamous, and small cell components, are etiologically related to high-risk HPV and can be identified by diffuse p16 expression. Pure vulvar and cervical adenoid cystic carcinomas appear to be unrelated to high-risk HPV and are distinguished from the mixed carcinomas by nondiffuse p16 expression.

Purpose To compare ultrasound biomicroscopy (UBM) versus anterior segment optical coherence tomography (AS-OCT) for imaging of tumors of the anterior segment of the eye. Design Retrospective, noninterventional case series. Participants We included 200 patients. Methods Review of medical records of patients who underwent both UBM and AS-OCT for evaluation of anterior segment tumors. Main Outcome Measures Comparison of tumor surface and internal visualization. Results There were 200 eyes with anterior segment tumors involving the iris stroma in 96 (48%), ciliary body in 14 (7%), combined iris and ciliary body in 32 (16%), iris pigment epithelium (IPE) in 44 (22%), conjunctiva in 6 (3%), sclera in 4 (2%), and others in 6 (1% each). The diagnoses included nevus in 75 eyes (38%), melanoma in 47 (24%), cyst in 48 (24%), epithelioma (adenoma) in 5 (3%), metastasis, melanocytosis and melanocytoma in 4 eyes each (2%), and others (1% each). Image analysis (UBM vs AS-OCT) revealed adequate visualization of all tumor margins (189 [95%] vs 80 [40%]), posterior tumor shadowing (9 [5%] vs 144 [72%]), and high overall image quality (159 [80%] vs 136 [68%]). Comparison for better image resolution (UBM vs AS-OCT) disclosed UBM provided better overall tumor visualization (138 [69%] vs 62 [31%]) and better resolution of the posterior margin (147 [74%] vs 53 [27%]), whereas AS-OCT provided better resolution of the anterior margin (40 [20%] vs 160 [80%]) as well as better overall resolution of anterior segment anatomy (41 [21%] vs 159 [80%]). Better resolution was found with UBM for pigmented tumors (n = 162; 107 [66%] vs 55 [34%]) as well as for nonpigmented tumors (n = 38; 23 [61%] vs 15 [39%]). Regarding location, iris tumor resolution was similar with each technique (49 [52%] vs 45 [48%]). Conclusions For anterior segment tumors, UBM offers better visualization of the posterior margin and provides overall better images for entire tumor configuration compared with AS-OCT. Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Background A cholesteatoma, also known as an epithelioma, is a mass of soft tissue that results from the accumulation of keratin protein debris enclosed by a layer of stratified squamous epithelium. Case Report A patient with cholesteatoma surrounding both internal carotid arteries presented with cerebral ischemic symptoms expressed as visual and ocular symptoms. Because of its location, mass effect, and potential stenosis of the internal carotids, this slow-growing tumor is potentially sight threatening. Asymmetric cupping of the optic nerves associated with symptoms such as dizziness, diplopia, or facial pain should be worked up carefully. Conclusion The primary care optometrist can play an important role in the diagnosis and continued management of a patient with a cholesteatoma, carefully monitoring early signs of progression or change. This case illustrates how an intracranial lesion, away from the eye, can impact a number of ocular and visual functions.

The case of a 53 year old female patient with metastasized androgen producing adrenocortical carcinoma is presented. After initial adrenalectomy a local relapse had been treated by surgery and external irradiation. Solitary liver metastases had been resected repeatedly. Subsequently multiple liver metastases required systemic chemotherapy. Treatment with o,p'-DDD (initially 12 g/d, long term treatment 1.5-3 g/d) has resulted in a complete remission for nearly 4 years. Gastrointestinal side effects occurred initially but subsided with dose reduction of o,p'-DDD.

— We examined the expression of mutant p53 gene products in primary malignant epithelial tumors of the liver. Fourteen of 68 hepatocellular carcinomas, one of seven hepatoblastomas and one of nine intrahepatic cholangiocarcinomas showed nuclear staining for p53 proteins. None of the surrounding non-tumorous tissues expressed nuclear staining. The detection of p53 proteins in tumor cells was significantly higher in hepatocellular carcinomas of Oriental patients (31.6%) compared to non-Orientals (6.7%, p

Our understanding of adenoid basal tumors of the cervix has evolved over time. Most of the proliferations referred to as adenoid basal carcinoma have a clinically benign course--leading some to suggest the term "adenoid basal epithelioma." However, rarely, these may be associated with invasive carcinomas. These tumors have been etiologically linked with high-risk human papillomavirus (HR-HPV) infection. Here, we investigate the use of p16 immunohistochemistry and HR-HPV RNA in situ hybridization (ISH) in the classification of adenoid basal tumors of the cervix. Seventeen cases of adenoid basal tumors of the cervix were included. The patients' age ranged from 19 to 79 yr (average, 59 yr). p16 immunostain was performed on all cases and RNA ISH was performed in 4 cases with available formalin-fixed paraffin-embedded tissue. There were 11 low-grade tumors, 5 frankly invasive carcinomas, and 1 with histologic features that were intermediate between the former 2 categories. p16 immunostain was negative or showed patchy cytoplasmic staining in the low-grade tumors and was strongly and diffusely positive in the invasive carcinomas. HR-HPV RNA ISH was negative in the 3 low-grade tumors and was positive in 1 case of invasive carcinoma including the adenoid basal component. Distinct p16 immunostaining and HR-HPV RNA ISH patterns exist between low-grade adenoid basal tumors and invasive adenoid basal carcinomas. Our study indicates that p16 immunostaining and HR-HPV RNA ISH can be employed as useful ancillary tools in differentiating between noninvasive and invasive adenoid basal tumors along with careful histopathologic evaluation.

Summary Although treatment of psoriasis with psoralen and ultraviolet A (PUVA) is associated with a long-term risk of development of cutaneous squamous cell carcinoma (SCC), the role of PUVA alone is not established, as many patients in reported series had also received treatment with other carcinogens, such as superficial X-rays or arsenic. We have recalled and examined 54 of the 63 patients still alive who have had PUVA treatment in our department, and who have been exposed to a cumulative UVA dose greater than 2000 J/cm2. None of the patients had been treated with superficial X-rays or arsenicals. Ten patients (19%) had developed SCC, and 25 (46%) had histologically atypical squamous keratoses arising at body sites similar to the carcinomas. The patients with SCC were significantly older at the start of PUVA treatment than those with keratoses alone. None of the 13% of patients without PUVA lentigines had keratoses or SCCs. These results show that high-dose PUVA treatment in the U.K., even when given alone, can frequently result in the development of SCC. Further malignancies are to be expected with continued follow-up of the patients with squamous keratoses. Absence of PUVA lentigines may be a useful indicator of a lower risk of PUVA malignancy.

Sixty-four patients (mean age, 51 years) had mastectomies which were synchronous and bilateral. Sixty-one premastectomy biopsies (bilateral, 34 and unilateral, 27) demonstrated the following: invasive carcinoma, 17; noninvasive carcinoma, 24; combination of above, 10; and benign disease, 10. Twenty-two patients had bilateral mastectomy because of bilateral positive biopsy. Twenty-nine patients with unilateral carcinoma on biopsy had bilateral mastectomy. Thirteen patients had bilateral mastectomy despite benign disease only on biopsy (10) or no biopsy (3). Ten unexpected carcinomas (34%) were found in the contralateral breast in the 29 patients with carcinoma diagnosed on unilateral biopsy. The biopsy pathology of these 10 spicemens was invasive ductal carcinoma in 1 and multifocal, noninvasive carcinoma(ductal, 3 and lobular, 6) in 9. An unexpected carcinoma may be found in the contralateral breast in a significant number of patients who are selected for bilateral mastectomy, particularly if the selection is on the basis of a noninvasive, lobular histology. Bilateral mastectomy may be appropriate for such patients, particularly when complicated by a strong family history and breasts which are difficult to assess by physical or mammographic examination.

Muir-Torre syndrome (MTS) is an autosomal, dominantly inherited disorder characterized by sebaceous neoplasms and visceral malignancies. We report a 56-year-old woman who underwent resections of extraocular sebaceous carcinoma, sebaceous epithelioma, actinic keratosis, and keratoacanthoma (KA)-like squamous cell carcinoma (SCC) with venous invasion metachronously over a 9-year period. Because of the mixed, unusual features of the skin lesions, and her history of endometrial and colorectal cancers that had been resected 12 years and 1 year, respectively, before the present event, a possible diagnosis of Muir-Torre syndrome was suggested. Immunohistochemical studies revealed loss of hMSH2 expression in all the cutaneous lesions including the actinic keratosis, and also in the endometrial and colorectal cancers. This patient presented with intriguing squamous lesions including keratoacanthoma-like squamous cell carcinoma that showed venous invasion and actinic keratosis, and associated loss of hMSH2 expression, in addition to the sebaceous neoplasms typical of Muir-Torre syndrome.

Background: Distinguishing basal cell carcinoma (BCC) from other benign and malignant skin tumors is sometimes a difficult task for the pathologists. Because the activation of hedgehog signals and the up-regulation of its critical transcriptional factor Gli1 are well documented in BCC, a molecular technique measuring Gli1 transcripts may aide the diagnosis. Methods: Gli1 transcript levels were measured by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using RNA extracted from formalin-fixed, paraffin-embedded tissues of 68 cases of various skin tumors. Hematoxylin and eosin-stained pathology slides were independently reviewed by three expert dermatopathologists. Results: The histological diagnoses were unambiguous in 53 tumors. The tumors included BCC (21), squamous cell carcinoma (13), seborrheic keratoses (8), trichoepithelioma (5), eccrine poroma/porocarcinoma (4), and sebaceous epithelioma/carcinoma (2). In these unambiguous cases, all BCC and trichoepithelioma tumors showed high expression of Gli1mRNA, while the expression was virtually absent in other tumors. The diagnosis was discordant among three pathologists in the remaining 15 tumors. Histological diagnoses included BCC, BCC with sebaceous differentiation, sebaceoma/sebaceous epithelioma, trichoblastoma, trichoepithelioma, basaloid follicular harmartoma, basosquamous carcinoma, etc. Six of them showed high Gli1 transcript levels. Conclusions: Quantification of Gli1 transcripts by RT-PCR is helpful in discriminating BCC and trichoepithelioma from other skin tumors.

Tuberculosis continues to be the biggest public health problem worldwide. Tuberculosis verrucosa cutis (TVC) is a verrucose form of cutaneous tuberculosis that occurs in previously sensitised individuals due to exogenous reinfection with Mycobacterium tuberculosis or Mycobacterium bovis, and it reflects good cell-mediated immunity. An elderly man presented with multiple fungating growths, which were painless but associated with mild itching and serous discharge, on the right foot for 40 years. The lesions were free from deeper structures and no inguinal lymphadenopathy was observed. A provisional diagnosis of epithelioma was made based on the features described. However, incisional biopsy indicated that the lesions were tuberculous. As part of the anti-tubercular therapy, the lesions were excised and the wounds covered with split-thickness skin graft. The patient's recovery was uneventful, with no graft loss or infection reported. This case illustrates the importance of recognising cutaneous forms of tuberculosis, especially TVC, as an important differential diagnosis of epithelioma.

Introduction: Superficial epithelioma with sebaceous differentiation is a rare benign epithelial neoplasm. It usually involves the head, neck or the back of a middle-age person. To the best of our knowledge, two ocular cases have been reported in the literature. Case presentation: A 46-year-old man of Italian descent, with a known history of testicular seminoma treated by orchiectomy with chemotherapy and radiotherapy, presented with a tan-colored lesion measuring 4mm in diameter in his right upper lid that had been growing over 10 months. It was clinically diagnosed as papilloma. An excisional biopsy was done. On histological examination, the lesion was a well-circumscribed and sharply demarcated epithelial tumor attached to the overlying epidermis and characterized by plate-like proliferation of basaloid to squamous cells with clusters of mature sebaceous cells and foci of ductal differentiation. After a follow-up period of 5 months, no recurrence of the lesion has been documented. Conclusions: Superficial epithelioma with sebaceous differentiation is part of the differential diagnoses of eyelid lesions. Arguments in the literature about the correct nomenclature of superficial epithelioma with sebaceous differentiation have resulted in under-diagnosed cases. The benign histological features and the lack of recurrence support its benign nature. Although no clear association has linked superficial epithelioma with sebaceous differentiation with Muir–Torre syndrome, further clinical correlation and close follow up for patients are recommended.

The objective of the present study was to demonstrate the safety and efficacy of a dermal replacement for cutaneous wounds of diverse origin. Autologous fibroblasts were cultured in fleece scaffolds made from benzyl esters of hyaluronic acid and applied onto cutaneous lesions. The cases presented are (1) skin removal for multiple epithelioma and (2) chronic deep decubitus ulcer. Dermal-like tissue applied by the surgeon elicited no adverse reactions, and was fully integrated and well-vascularized by 1-3 weeks. In Case 1, the material was fully integrated after 1 week, and after 3 weeks an epidermal autograft was overlaid which showed good take with excellent integration observed after 4 weeks. At 12 months, skin demonstrated visual normo-elastic properties and no signs of excessive scarring. In Case 2, 2-3 weeks after the dermal implant was applied, the wound was invaded with granulation tissue and healing occurred by secondary intention. The ulcer was healed by 8 weeks, with the biomaterial completely resorbed and a complete re-epithelialization over the dermal-like tissue. These results suggest that autologous fibroblast culture in hyaluronan-derived scaffolds may be successfully grafted in diverse cutaneous pathologies and constitute a suitable bed for further epidermal implantation.

A series of 12 adenoid basal carcinomas and three adenoid basal hyperplasias of the cervix were analyzed. The ages of the patients with adenoid basal carcinoma ranged from 30 to 91 years with a mean of 71 years. Pap smear results for 11 of 12 (92%) were abnormal. Almost all patients were asymptomatic. None had a gross cervical tumor. All tumors had typical histologic features of adenoid basal carcinoma, with various degrees of squamous differentiation. Depth of tumor invasion ranged from 2 mm to 10 mm (mean, 4.3 mm; median, 3.7 mm), exceeding 3 mm in six tumors (50%). Tumor volume was >500 mm3 in four tumors (33%). An associated neoplastic squamous lesion was present in 92% of patients, including high-grade cervical intraepithelial neoplasia in 10 cases and microinvasive squamous cell carcinoma in one. Treatment was predominantly surgical, usually after some form of cervical conization; conization alone was performed in three patients. Lymph nodes were removed in five patients; none of 104 nodes had metastases. No recurrence of tumor developed in any patient. Nine patients were alive without disease after 4 to 82 months (mean, 30 months), and three died without disease after 24, 63, and 87 months. The three patients with adenoid basal hyperplasia also were asymptomatic and did not have a gross cervical lesion. Pap smear results for two patients were abnormal. The adenoid basal hyperplasias were incidental, very superficial lesions that resembled small adenoid basal carcinomas. Generally, they were attached to the squamous or endocervical mucosal epithelium; all were less than 0.5 mm in depth. Treatment was hysterectomy in one patient and conization in two. Follow-up was short but uneventful. Our findings, together with those previously reported, indicate (1) adenoid basal carcinoma with typical histologic features is not a malignant neoplasm in that it typically presents in asymptomatic women, usually is discovered after an abnormal Pap smear result due to cervical intraepithelial neoplasia, does not produce a grossly visible lesion, has never metastasized to regional lymph nodes or elsewhere, and has never itself caused death; (2) rare, histologically atypical tumors with distinctly malignant features should not be regarded as adenoid basal carcinoma; and (3) adenoid basal hyperplasia probably is a small adenoid basal carcinoma. We propose the term "adenoid basal epithelioma" to replace adenoid basal carcinoma and adenoid basal hyperplasia, because it better describes the clinicopathologic features of these distinctive lesions and their excellent prognosis and may reduce the likelihood of unnecessarily aggressive treatment.

We present a case of giant calcifying epithelioma of Malherbe (pilomatrixoma) in the right upper arm of a 62-year-old man. It measured 18 x 12 x 8 cm in size, making it the largest of all the cases reported previously. CT clearly demonstrated a well-defined, subcutaneous mass with amorphous calcifications. The mass showed intermediate signal intensity on T2*-weighted MR images and slight contrast uptake on contrast-enhanced MR images. Histopathologically, this tumor showed no aggressive or malignant nature. The patient is without evidence of recurrence or metastasis 3 years following the resection.

Objective To characterize the cytomorphologic features of pilomatrixoma. Study design Aspirate findings in nine cases of PMX were correlated with clinical data and subsequent histology. This relatively large volume of case material afforded an opportunity to test the cytologic criteria that have been proposed as diagnostic of pilomatrixoma in the case reports published previously. Results Ghost cells, basaloid cells and calcium deposits were the features found to be most characteristic of PMX and were observed in all four cases in which a correct diagnosis was made originally. Conclusion The presence of ghost cells seems to be the key to recognizing PMX. These cells are visible in the majority of air-dried smears but seldom in alcohol-fixed smears. Adequate cytologic sampling and the routine use of both wet-fixed and air-dried smears should preclude an incorrect diagnosis.

Mixed gliomas have been difficult to define and subsequently diagnose due to the paucity of literature specifically examining this group of tumors. Thirty mixed gliomas in which the minor glial component comprised at least 20% of the total tumor were studied: 20 oligoastrocytomas (OA) and ten malignant oligoastrocytomas (MOA). Nineteen patients were male (mean age 36 years) and 19 patients (63%) presented with seizures. The tumor was located in the frontal lobe in 17 patients (57%) and the temporal lobe in nine patients (30%). The duration of preoperative symptoms in 25 patients ranged from five days to 14 years (mean 2.6 years). A mean follow-up of four years was available in 29 patients. Fourteen patients, seven with OA and seven with MOA, had recurrent tumor. One patient with MOA and four patients with OA (three with tumor progression and one with extensive leptomeningeal spread) died as a result of their tumor one to five years after diagnosis. Eighteen patients received chemotherapy and/or radiation therapy. Twenty-five tumors were immunostained with antibody to p53 protein. p53 nuclear staining was seen in 5/16 OA (31%) and 3/9 MOA (33%). Positive staining was observed only in astrocytic appearing cells. One of the four patients who died with OA was p53 positive. Three recurrent MOAs were p53 positive. Our study indicates that: 1. mixed gliomas most frequently occur in the frontal lobe and the majority of patients present with seizures; 2. there is no obvious association of p53 detection in mixed gliomas with tumor grade or behavior; and 3. similar to pure fibrillary astrocytomas, a subset of OA and MOA may be associated with p53 alterations.

The aim of our study was to elucidate the role of Rap2B in the development of human suprarenal epithelioma and to investigate the effect of Rap2B on suprarenal epithelioma cells migration and invasion. We use tissue microarray and immunohistochemistry to evaluate Rap2B staining in 75 suprarenal epithelioma tissues and 75 tumor-adjacent normal renal tissues. And the expression of Rap2B protein in human suprarenal epithelioma cells and tissues was detected by western blot simultaneously. The role of Rap2B in suprarenal epithelioma cells migration and invasion was detected by using wound healing assay, cell migration assay, and matrigel invasion assay. After that, we performed western blot analysis and gelatin zymography to detect MMP-2 protein expression and enzyme activity. Our research showed that Rap2B expression was increased in tumor tissues compared with tumor-adjacent normal renal tissues. But no correlation was found between Rap2B expression and clinicopathological parameters. In addition, we found that Rap2B promoted the cell migration and invasion abilities, and Rap2B increased MMP-2 expression and enzyme activity in suprarenal epithelioma cells. Our data indicated that Rap2B expression is significantly increased in human suprarenal epithelioma and Rap2B can promote the cell migration and invasion abilities, which may provide a new target for the treatment of suprarenal epithelioma.

Intracavitary brachytherapy is an effective treatment for gynecologic cancers. Twelve magnetic resonance (MR) imaging studies were performed during intracavitary brachytherapy (10 initial studies and two during repeat brachytherapy) in 10 patients with clear cell adenocarcinoma (n = 9) or epithelioma (n = 1). Fifty percent of the vaginal lesions did not demonstrate high signal intensity on T2-weighted images. Individually tailored molded applicators allowed easy detection of abnormal vaginal parietal thickening on T1-weighted images: Results in seven cases were concordant with results of clinical examination, and there were no false-negative results. MR imaging was useful in controlling the relationships between the tumor and the applicator and facilitated treatment planning, since the radiation dose to the tumor volume and adjacent critical organs could be calculated accurately. Limitations of MR imaging were underestimation of superficial vaginal tumors and the inability to differentiate between tumor and inflammation after recent surgery or repeat intracavitary brachytherapy. MR imaging during intracavitary brachytherapy appears to be a useful adjunct to clinical examination.

Background: Sebaceous epithelioma is a benign tumor that must be differentiated from basal cell carcinoma and other appendageal tumors. Objective: Histologic and clinical findings were reviewed in 21 patients with sebaceous epitheliomas. Methods: Twenty-one cases of sebaceous epithelioma collected during a 5-year period were reviewed. Results: The tumors appeared as yellow to flesh-colored papules, most often on the face and neck. They consisted of basaloid cells with foci of sebaceous differentiation. Cystic spaces formed by holocrine degeneration or simulating sebaceous duct lining were common findings. Patients with sebaceous epitheliomas were more likely than the general population to have an internal malignancy. Conclusion: Patients with sebaceous epithelioma should be examined for an underlying malignancy.

The Muir-Torre syndrome is characterized by cutaneous neoplasms and visceral malignancies. At least one sebaceous adenoma, epithelioma or carcinoma and at least one internal malignancy are required to make a reliable diagnosis. According to medical literature only two cases of Muir-Torre syndrome with jejunal carcinoma have been reported to date and there is no reported case with intestinal obstruction. Here, we report an unusual case of jejunal carcinoma presenting with ileus.

Background. The patient with nasopharyngeal carcinoma (NPC) frequently is initially seen with regional node dissemination. Preliminary investigations suggest that the presence of Epstein-Barr virus (EBV) genomes in neck metastases from an occult primary may be diagnostic and predictive of NPC. The goal of this study was to test this proposition. Methods. The polymerase chain reaction (PCR) was used to detect the presence of EBV DNA in fine-needle aspirate (FNA) samples obtained from malignant neck nodes. Control samples were obtained from other locations in the head and neck. Patients. The patients in this study were evaluated at the Toronto Princess Margaret Hospital, a province-wide tertiary care cancer treatment center. Of the 23 patients evaluated with malignant neck masses, 6 had NPC, 5 patients had metastatic squamous cell carcinoma of an unknown primary, and 12 patients served as controls with other known head and neck carcinomas. One of the patients initially diagnosed as an unknown primary later demonstrated NPC. FNA specimens were also obtained from 24 normal parotid, submandibular, or thyroid glands for comparison. Results. In the samples with sufficient DNA for analysis, EBV was detected in 5 of 5 neck nodes from patients with known NPC. EBV was also detected in the neck node of a patient who went on to develop NPC and in a cervical node from 1 of 2 patients in whom the primary tumor remained unknown. None of the evaluable control neck nodes or FNA controls from other sites demonstrated EBV. Conclusions. These results demonstrate the utility of NPC-diagnostic EBV gene amplification in FNA samples of neck metastases and suggest that the presence of the EBV genome in FNA samples of neck nodes is predictive of the presence of NPC. © 1995 Jons Wiley & Sons, Inc.

Background. More than one-third of patients with localized renal cell carcinoma (RCC) will have disease progression after nephrectomy. Present histopathologic variables cannot accurately predict the outcome of individual patients. Methods. Nuclear morphometry was performed by an image analyzer on histologic sections from 39 specimens of pathologic T1 and T2 classification RCC. All patients underwent radical nephrectomy and were followed for a mean of 7.6 years. A univariate analysis and then a multivariate stepwise regression method were used to correlate results with patients' outcome. Results. The best predictors of disease free interval were mean nuclear elongation factor (MNEF) (P = 0.023), mean nuclear regularity factor (MNRF) (P = 0.034), and mean nuclear area (MNA) (N = 0.038). Univariate analysis identified a significant correlation between patient survival and MNEF (P = 0.009), MNRF (P = 0.020) and MNA (P = 0.023). Combination of MNEF and MNA was even more strongly associated with survival (P = 0.0013). Multivariate analysis revealed that MNA (P = 0.044) and MNEF (P = 0.045) correlated independently with survival. Conclusion. These results suggest that nuclear morphometry provides objective independent prognostic information for patients with localized RCC.

To quantify dynamic enhancement of breast lesions with echo-planar and conventional magnetic resonance (MR) imaging, to correlate these data with histologic findings and vessel density, and to evaluateTwenty female patients with 22 breast lesions underwent conventional and MR echo-planar imaging T1 values, change in gadopentetate dimeglumine concentration, and extraction-flow products were calculated with echo-planar imaging data and were correlated with histologic findings and microvessel density.T1 values of cancers were not statistically significantly shorter. Cancers had more rapid uptake and higher extraction-flow products (P.02). Sensitivity was 86% and specificity was 93% for diagnosis of malignancy. Microvessel density was higher for malignant lesions (P.02) with an overall positive (not statistically significant) correlation between extraction-flow product and microvessel density.Echo-planar imaging appears promising for quantification of breast lesion enhancement. Microvessel data indicate that tumor angiogenesis affects enhancement.

To quantify color Doppler (CD) signals reflected by breast lesions to improve differential diagnosis and serial comparisons.Frame-grabbed color-capture scans were remapped to original velocities on a pixel-by-pixel basis for statistical analysis. Total CD area and its percentage, peak and mean velocities, standard deviation of velocity, and integral CD velocity and its percentage were calculated. These indexes were applied to scans of 44 cancers, 16 fibroadenomas, and 14 benign breast changes in 74 patients.With the region of interest confined to the lesion and a 5-mm margin, no CD signals were reflected by the benign breast changes. All carcinomas and 12 fibroadenomas (those that were vascular) reflected CD signals, and, except for mean and peak velocity, all scores for cancers were significantly higher than for fibroadenomas (P.0001). Integral CD velocity was the best discriminator, with no overlap between carcinomas (range, 1,128-50,228 cm3/sec) and fibroadenomas (range, 0-1,027 cm3/sec).Automatic CD quantification improved differential diagnosis of breast masses.

A technique has been developed for the detection of tumour cells in blood with the magnetic activated cell sorter (MACS). Colonic carcinoma cell lines and disaggregated primary tumours were used to establish optimal conditions of separation. A murine monoclonal antibody specific for epithelial cells was added to the suspension of leucocytes and tumour cells, followed by magnetic labelled goat antimouse antibody. The labelled tumour cells were retrieved by passing this suspension through a MACS separation column in a strong magnetic field. Tumour cells were detected at a dilution of 10 cells per ml blood. Tumour cells were identified in mesenteric blood in three of 24 patients undergoing surgery for colorectal cancer. This study supports the use of the MACS to detect circulating tumour cells.

A total of 128 surgically resected small hepatocellular carcinomas, measuring less than or equal to 3 cm in diameter, were studied by both macroscopic and histologic examinations. In 95 single nodular-type tumors of the 128 lesions, eight tumors were associated with the cancerous areas of well differentiated hepatocellular carcinoma around the nodule. These surrounding cancerous areas went undetected by both the preoperative radiological examinations and the gross findings of resected specimens. Based on the immunohistochemical findings, the labeling index, both of the proliferating cell nuclear antigen (PCNA) and of the Ki-67 in the surrounding cancerous areas, were lower than that of the main nodules but higher than in the nontumorous liver parenchyma in seven of eight cases. These results suggest that the main nodule was generated from the surrounding cancerous area, supporting the hypothesis of a stepwise progression of HCC. Even if the tumor seems to be a small and single nodular type, it is recommended that its surrounding areas should be closely examined and the surgical cutting margin should be made more than 1.0 cm away from the main nodule at hepatic resection.

High-resolution flow cytometric (FCM) DNA analysis was performed on 148 unfixed, frozen tissue samples from four groups of early breast cancers: invasive carcinomas (ICs) with predominance of carcinoma in situ (DCIS) (group I), small clinical cancers < or = 15 mm (group II), node-negative, clinical cancers (group III) and small screening-detected cancers < or = 15 mm (group IV). The median tumour size was 12 mm. The aim of the study was to support, with a larger sample, our recent findings with respect to DNA ploidy pattern in the selected group of ICs with predominance of DCIS (group I). Similar results to this group were found for both the small clinical cancers and the node-negative cancers, with respect to frequency of DNA aneuploidy (79% and 90%), DNA index (DI) distribution, intratumoral DNA heterogeneity and S-phase fraction. A high frequency of DNA hyperdiploid clones was found, in particular related to highly differentiated tumours. A significant difference was found compared with the screening-detected cancers, which were characterised by a much lower frequency of DNA aneuploid samples (49%) and may represent a biologically specific group of low-malignant, slowly growing tumours. Associations were shown between histological grade and DI subclasses, and between lymph node status and DNA diploidy/aneuploidy, whereas DI was not correlated with tumour size. The DNA ploidy findings in this series of early cancers are concordant to our own results from preinvasive lesions as well as those reported from series of more advanced cancers.

PURPOSE: To define indications for percutaneous ethanol injection (PEI) in patients with hepatocellular carcinoma (HCC) and cirrhosis. MATERIALS AND METHODS: Survival rates were determined in 746 patients who had undergone PEI (567 men, 179 women; mean age, 64.3 years; mean follow-up, 36 months). RESULTS: In patients with Child A (n = 293), B (n = 149), or C (n = 20) cirrhosis and single HCCs 5 cm or smaller, the 3-5 year survival rate was 47%-79%, 29%-63%, and 0%-12%, respectively. In patients with Child A cirrhosis, it was 36%-68% for multiple HCCs (n = 121), 30%-53% for single HCCs larger than 5 cm (n = 28), and 0%-16% for advanced HCC (n = 16). Treatment was associated with a 1.7% rate of severe complications and a 0.1% mortality rate. CONCLUSION: PEI proved safe, effective, and repeatable and had a low cost. Survival after PEI was comparable to that after surgery, probably because of a balancing between greater radicality of surgery and absence of early mortality and liver damage of PEI.

The relationship between morphometric and clinical data was assessed in a series of 60 advanced ovarian carcinomas. Morphometric parameters included nuclear area, nuclear perimeter, shortest and longest nuclear axis, roundness coefficient, volume percentage of epithelium (VPE) and mitotic index. All patients had at least 5 years of follow-up. Univariate survival analysis showed that FIGO stage (P < 0.001), VPE (P < 0.001), mean nuclear area (P < 0.001) and size of residual tumour (P < 0.001) are significantly associated with survival. When the response rate of these patients to cisplatin combination chemotherapy was evaluated, variables with good prognostic outcome were residual tumour size (P = 0.01), mean nuclear area (P = 0.0006) and s.d. of nuclear area (P = 0.0019). We conclude that morphometric parameters are able to support diagnostic and therapeutic decisions.

The purposes of this study were to analyze the CT features of scirrhous carcinoma of the gastrointestinal (GI) tract and to assess the usefulness of CT in detecting and staging these lesions.This is a retrospective evaluation of 31 proven cases of scirrhous carcinoma (linitis plastica) of the GI tract imaged in our institution from 1986 to 1994. Twenty-two patients had primary gastric carcinoma, and nine had carcinoma of the colon (rectosigmoid in eight and right colon in one). CT examinations were reviewed and correlated with pathologic and/or surgical findings in all patients and with barium examinations in 19 cases. A modified Dukes classification was used to stage these lesions without knowledge of the pathologic and surgical results.Four gastric lesions were missed during the initial CT examination. Seventeen patients had extensive circumferential lesions, and five had focal plaquelike lesions. The wall thickness ranged from 1 to 3 cm (mean, 1.8 cm). Homogeneous enhancement was seen in 17 patients, slightly heterogeneous enhancement was seen in one, a target configuration was present in two patients, and intramural calcification was present in one patient. All colonic lesions were circumferential, homogeneously enhancing with a wall thickness ranging from 1 to 3 cm (mean, 2 cm). CT scans showed limitations in evaluating local parameters. Compared with surgical and pathologic staging, CT correctly staged 26 patients, understaged four patients, and overstaged one patient. Among the 19 patients with pathologically proven stage D lesions (61%), CT correctly staged 17 patients (89%) and had a 100% positive predictive value. One case of hepatic metastases, 13 cases of malignant ascites, and 11 cases of omental and peritoneal metastases were found.CT is an important complimentary imaging technique to detect scirrhous carcinoma. The sensitivity of detection depends on the size of the lesion and the quality of the examination. CT has limitations in staging early lesions but shows a high sensitivity (89%) in detecting Dukes stage D lesions. Accurate CT staging in these individuals (61% in this series) allows a more adequate treatment strategy and avoids unnecessary exploratory laparotomies.

Ninty-two patients with locally advanced stages IB, IIA, and IIB cervical cancers, who had completed 4 years of follow-up after treatment with preoperative adjuvant chemotherapy prior to radical surgery, were compared with 138 patients in same disease status who were treated with radical surgery without preoperative adjuvant chemotherapy. In the patients treated with preoperative adjuvant chemotherapy (VBP scheme), the chemotherapeutic response was more favorable in squamous cell carcinomas (87%) than that in adenocarcinomas (38%). The detection rate of pelvic lymph node metastasis from the surgical specimens of radical operation was higher in the patients of radical surgery without preoperative chemotherapy (34%; 47/138) than that in the preoperative adjuvant chemotherapeutic patients (17%; 16/92, P = 0.005). Recurrence occurred in 50 of 138 patients (35.5%) who were treated by radical surgery without preoperative chemotherapy and in 17 of 92 patients (18.5%) who were treated with preoperative adjuvant chemotherapy followed by radical surgery. The difference of recurrence rate between two groups was statistically significant ( P = 0.004). The tumor-free survival of preoperative adjuvant chemotherapeutic patients was significantly longer than those in the patients without preoperative chemotherapy ( P = 0.0067). Tumor response to chemotherapy was a valuable prognostic factor in management of patients and preoperative adjuvant chemotherapy was beneficial in reducing pelvic lymph node metastases, reducing recurrences, and prolonging the survival of the patients with locally advanced cervical cancers, especially in stage IIA.

Background Concanavalin A (Con A) affinity electrophoresis of serum alpha-fetoprotein (AFP) can distinguish hepatocellular carcinoma (HCC) from other malignancies when the serum AFP concentration is elevated. However, Con A has not been able to distinguish HCC from benign chronic liver disease such as cirrhosis or chronic hepatitis. Methods The Con A affinity electrophoresis of serum AFP was analyzed in patients with a serum AFP concentration greater than 50 ng/mL by antibody affinity electrophoresis and Western blotting in an attempt to distinguish hepatocellular carcinoma from benign chronic liver disease. Before the assay, the serum AFP concentrations were adjusted between 100 ng/ml and 300 ng/ml by concentrating or diluting the samples. Results Of 180 patients with HCC, 44 (24%) had a single band and 91 (51%), 35 (19%), and 10 (6%) had 2, 3, and 4 bands, respectively. All 35 patients with chronic hepatitis had a single band. All but 1 of 72 patients with cirrhosis had a single band. Multiple AFP bands on Con A affinity electrophoresis appear to be diagnostic of HCC. This method has a sensitivity of 76%, a specificity of 99%, a positive predictive value of 99%, and a negative predictive value of 71% for detecting HCC. The number of AFP bands correlated with serum AFP concentration and tumor size in patients with HCC. Conclusions This assay is useful for distinguishing HCC from benign chronic liver diseases.

Objective: In the search for the optimal treatment of advanced cervical cancer, the identification of valid prognostic factors obtainable without histopathologic investigation of the entire tumor and the locoregional lymph nodes is of paramount interest. Tumor microvessel density has recently been demonstrated to correlate strongly with disease aggressiveness in breast cancer and other malignancies. Methods: We established a computerized image analysis system to quantify tumor microvascularity by using the closest-individual method, which determines the distribution of distances from random points within the tumor to the closest microvessel (DTCMV). Tumor microvascularity was assessed in paraffin sections of two cylindrical 2 × 20-mm core biopsies obtained transvaginally from the 12 and 6 o'clock positions of each tumor and then immunohistochemically stained for Factor VIII-related antigen. The oncologic relevance of tumor vascularity is studied in an open prospective trial. Results: Tumor vascularity was quantified in 42 patients with cervical cancers >3 cm in largest diameter, FIGO stages Ib-IVa. This new parameter representing pathophysiological tumor-host interactions was independent of various other patient and tumor characteristics, including age, FIGO stage, tumor size, differentiation, lymph node metastases and lymphatic space involvement. Thirty-nine patients were treated with curative intent either by primary surgery (n = 22) or radiation (n = 17). After a median observation time of 18 months (range 441 months), the patients with higher tumor vascularity (mean DTCMV

Background. Hurthle cell tumors still pose issues concerning diagnosis and management. Methods. From 1984 to 1993 forty-seven patients underwent thyroidectomy, and they were diagnosed after operation to have presumptive Hurthle cell tumors. The surgical pathologic findings were reviewed. In the neoplastic group the chart was reviewed for clinical features and outcome. Results. Thirty-one patients had nonneoplastic Hurthle cell nodules. Eleven (69%) of the 16 tumors were malignant affecting 11 women and five men ranging in age from 22 to 86 years. Two patients died of cancer for a 18% rate; one patient is alive with disease. Operations were uncomplicated. Factors for adverse outcome include tumor size greater than 4 cm, woman older than 60 years of age, and complete capsular invasion on surgical pathologic findings. Conclusions. Fine-needle aspiration biopsy demonstration of Hurthle cell lesion is an indication for operation, providing Hashimoto's thyroiditis is excluded. Our surgical practice (I.B.R.) is to perform total thyroidectomy for all Hurthle cell neoplasms, as well as jugular node sampling and adjuvant radioiodine for cancer. Stringent histologic interpretation is possible and necessary for true appreciation of Hurthle cell tumor incidence and behavior. Cancer mortality of 18% is greater than the rate (2%) of our well-differentiated thyroid cancer group.

Background. E-cadherin (ECD) is known to be an invasion suppressor gene, and urokinase-type plasminogen activator (uPA) plays a central role in infiltration of solid cancers. Methods. To elucidate the relationship between expression of these factors and metastasis in patients with gastric cancer, the authors examined immunohistochemically a combination analysis of uPA and E-cadherin expression in 98 primary tumors, and the results were correlated with several parameters related to metastasis. Results. Among 125 tumors, 42 (34%) were evaluated as having E-cadherin expression (E-cadherin-positive), and the other 83 (66%) were defined as having reduced E-cadherin expression (E-cadherin-negative). uPA immunoreactivity was observed in 82 tumors (66%). There were four subtypes of patterns of uPA and E-cadherin expression: 22 uPA-negative/E-cadherin-positive, 17 uPA-negative/E-cadherin-negative, 21 uPA-positive/E-cadherin-positive, and 65 uPA-positive/E-cadherin-negative. uPA overexpression and reduced E-cadherin expression were associated with lymph node metastasis, vessel invasion, serosal involvement, and poor prognosis. In addition, uPA-positive/E-cadherin-negative tumors were associated significantly with large tumors, positive serosal invasion, lymph node involvement, and poor prognosis. Patients with uPA-positive/E-cadherin-negative expression had the poorest prognoses, compared with the three other groups of patients. uPA-positive/E-cadherin-negative tumors had a fourfold relative risk of death when compared with uPA-negative/E-cadherin-positive tumors. A Cox proportional hazard model projected lymph node status as the strongest of the prognostic variables, followed by DNA ploidy patterns and uPA/E-cadherin tissue status. Conclusions. These results indicate that immunohistochemical combination analysis of uPA and E-cadherin expression may be a powerful aid in evaluating meta-static potential or the prognosis of patients with gastric cancer. Cancer 1995;76:941–53.

Both preoperative cytological (FNS) and tumorectomy surgical specimens of the same tumor were obtained from 89 patients with breast cancer. Estrogen and progesterone receptors were assayed on cytosolic extracts by enzyme immunoassay (EIA), in 89 patients for estrogen and in 68 patients for progesterone. Both concentrations were highly correlated between the FNS and the corresponding surgical sample, but FNS values yielded 2 to 3 times higher. With cut-off values of 250 fmol/mg DNA, corresponding to 15 fmol/mg cytosol protein for surgical samples and 500 fmol/mg DNA for FNS, the receptor status was concordant between the types of samples in 84 of 89 (94%) and 59 of 68 (86.8%) patients for estrogen and progesterone, respectively. Sixty-seven carcinomas were estrogen positive, 17 estrogen negative, 38 progesterone positive, and 21 were progesterone negative in both samples. The authors conclude that estrogen and progesterone EIAs can be performed on FNS provided by properly trained pathologists, with a control of their cellularity by DNA assay.

The gene expression of two type IV collagenases (matrix metalloproteinase [MMP]-2, a 72 kd type IV collagenase, and MMP-9, a 92 kd type IV collagenase) was investigated in carcinomas of the hypopharynx. We examined 27 cases operated on in our hospital by an in situ hybridization technique to detect their messenger RNA signals in cancer cells and surrounding stroma. Both signals were detected in all cancer nests and in stromal cells in the same specimens. Clinicopathologic studies showed a significant relationship between MMP-2 expression in the primary cancer and the outcome of treatment. Our present study suggests that hypopharyngeal squamous cell carcinoma producing MMP-2 has a high potential for invasion and metastasis and a poor outcome. The analysis of MMPs will be useful for treatment planning in hypopharyngeal carcinoma and for prognosis.

The purpose of this study was to evaluate the role of ultrasonography in differentiation between the echogenic characteristics of carcinoma and those of fibroadenoma of the breast. Two mathematical transformations of the measured density on a sonographic image of the breast lesion at three different system gain settings were used in cases of carcinoma (n = 16) and fibroadenoma (n = 31) to provide standardized density values. A significant correlation was found between the tumor and the surrounding tissue densities in both carcinomas (r = 0.77, P = 0.0004) and fibroadenomas (r = 0.79, P < 0.000001. The mean standardized density of the tumor was significantly higher (P < 0.0001) than the surrounding tissue in both carcinomas (2.03 +/- 0.64 D versus 1.23 +/- 0.38 D) and fibroadenomas (2.09 +/- 0.48 D versus 1.33 +/- 0.3 D). However, the differences between density values of carcinoma and fibroadenomas were not significantly different. The data suggest that it may not be possible to differentiate breast carcinoma and fibroadenomas on the basis of the echogenicity of solid breast masses.