Association of sexually transmitted infections and human papillomavirus co-infection with abnormal cervical cytology among women in Saudi Arabia.

Human papillomavirus (HPV) is a causative agent of cervical and other cancers. Sexually transmitted Infections (STIs) may play a crucial role in HPV persistence, leading to serious complications, including cervical cancer. This study investigated the association of HPV/STI co-infection in cervical samples with cervical dysplasia among women in Saudi Arabia. HPV-positive cervical samples (n = 142) were obtained from previous studies and newly collected samples (n = 209) were obtained from women aged 19-83 years. For HPV detection and genotyping, PCR and Genoflow HPV assay kits were used. STIs were detected using a Genoflow STD array kit. Of 351 samples, 94 (27%) were positive for STIs. Among HPV-positive samples, 36 (25%) were positive for STIs; the most common pathogens were Ureaplasma urealyticum/Ureaplasma parvu (13%) and Mycoplasma hominis (6%). A global significant correlation was detected between HPV and STIs with progression of abnormal cervical cytology (χ2 = 176, P < 0.0001). Associations between cervical cytology diagnosis and HPV status, STI types (opportunistic and pathogenic), and the presence of Ureaplasma spp., and Mycoplasma hominis were significant (P < 0.05). Our results suggest that additional study in a larger population is warranted to determine the association between HPV/STI co-infection and cervical neoplasia in Saudi women.

Human papillomavirus type 16 and 18 viral loads as predictors associated with abnormal cervical cytology among women in Saudi Arabia.

The detection of HPV viral DNA is regularly conducted with cervical screening. However, using a molecular marker such as the viral load may serve as a predictor associated with disease detection and progression. The present study aimed to screen for and genotype HPV among women in Saudi Arabia, develop and validate sensitive quantitative polymerase chain reaction (qPCR) assays to detect viral load for the two most common HPV types, namely 16 and 18, and assess whether HPV viral load could be used as a marker for cervical abnormality and disease progression. This study examined 733 specimens (both formalin-fixed paraffin embedded specimens and PAP smear samples) from women who underwent cervical screening. The specimens and samples were processed for DNA extraction and then tested for HPV DNA using nested PCR. Approximately 165 specimens (18%) were positive for HPV. Those specimens were genotyped using a reverse line blotting hybridization assay. The results indicated that the most common HPV types detected were a single infection with HPV 16 (51%) or with HPV 18 (28%) followed by infections with multiple HPV types (~7%). A qPCR TaqMan assay developed and validated in-house was used to determine viral load for HPV genotypes 16 (n = 80) and 18 (n = 45). Viral loads for both HPV types were significantly associated with cervical cytology grade (P < 0.05). The odds ratio (OR) for the HPV 16 viral load was high for specimens with cervical cancer (OR, 18.8; 95% CI, 4.3-82.9) or for those with high-grade squamous intraepithelial lesions (OR, 14.7; 95% Cl, 2.43-88.49). For the HPV 18 viral load, the OR was significant only for specimens with cervical cancer (OR, 11.1; 95% Cl, 2.2-54.9). Logistic regression models for HPV 16 and for HPV 18 viral load levels were significant, with higher viral load associated with cervical abnormalities. These findings indicate that viral load is a predictor significantly associated with cytology abnormality in women who are positive for high-risk HPVs and suggest that integrating a viral load test into current clinical screening practices for HPV-positive women is warranted in Saudi Arabia.

A retrospective study of malignant melanoma from a tertiary care centre in Saudi Arabia from 2004 to 2016.

BACKGROUND: Malignant melanoma is a well-known and commonly lethal tumour yet there exists scarce published information available from Saudi Arabia. MATERIALS AND METHODS: This study examined the demographic, clinical, and histopathological profile of melanoma in a sample of Saudi patients over a period of 13 years. Medical records of 98 patients from 2004 to 2016 were retrieved from the Department of Pathology and Laboratory Medicine at King Faisal Specialist Hospital (KFSH), Riyadh, Saudi Arabia. RESULTS: Forty two males and fifty six females (median age of 58 years) were analysed. Most cases were diagnosed in patients aged 50 years or above. The most common sites of occurrence were the extremities, especially the feet, followed by the head and neck, and then mucosal regions. Most mucosal melanomas were located in the mouth. The most common histopathological form was nodular melanoma (38 cases) followed by acral lentiginous melanoma (27 cases). Most of the cases were diagnosed in late diagnostic stages III and IV (59 cases) and most had higher Clark's level and stage V Breslow thickness. The cases with preceding history of xeroderma pigmentosum and dysplastic nevi tended to be diagnosed earlier. The most common mode of treatment was surgical resection. Patients on palliative treatment were older. Only 27/40 patients were confirmed to be alive and the rest were lost to follow-up. CONCLUSION: Our data contrast with previously published studies from other parts of the world. Further work is needed to confirm our findings of female preponderance, common histological subtypes of nodular and acral melanomas, and the high involvement of oral mucosa in our Saudi patients.

Sociodemographic characteristics and sexual behavior as risk factors for human papillomavirus infection in Saudi Arabia.

OBJECTIVES: To determine the prevalence and the sociodemographic characteristics and sexual behavior risk factors for human papillomavirus (HPV) infection in a hospital-based cohort of women in Saudi Arabia. METHODS: Cervical specimens and questionnaire data were collected from women attending clinics in Riyadh, Saudi Arabia. Cervical specimens were examined for abnormal cytology using a standard Pap test and for the presence of HPV-DNA using PCR and reverse line blot hybridization tests. RESULTS: Approximately 73% of the 400 women tested were Saudi nationals. Nearly 50% were under 40 years old (range 22-80 years, mean±standard deviation 41.20±10.43 years). Approximately 17% of the women were HPV-positive. The most commonly detected HPV types were HPV-18 (34%) and HPV-16 (19%), with multiple infections detected in 10% of positive specimens. Multivariate analyses revealed that smoking and multiple partners were significant risk factors for HPV infection (p<0.01). CONCLUSIONS: Because of societal challenges and an unsubstantiated assumption of low HPV prevalence, few studies have examined sociodemographic characteristics or sexual behaviors associated with HPV in Saudi women. However, a high prevalence of HPV infection was found, with smoking and multiple partners as significant risk factors, in this hospital-based cohort of predominantly Saudi women.

Fascin is involved in the chemotherapeutic resistance of breast cancer cells predominantly via the PI3K/Akt pathway.

BACKGROUND: A major therapeutic challenge for breast cancer is the ability of cancer cells to evade killing of conventional chemotherapeutic agents. We have recently reported the actin-bundling protein (fascin) as a major regulator of breast cancer metastasis and survival. METHODS: Survival of breast cancer patients that received chemotherapy and xenograft tumour model was used to assess the effect of chemotherapy on fascin-positive and -negative breast cancer cells. Molecular and cellular assays were used to gain in-depth understanding of the relationship between fascin and chemoresistance. RESULTS: We showed a significant correlation between fascin expression and shorter survival in breast cancer patients who received chemotherapy. In xenograft experiments, fascin-positive cancer cells displayed significantly more resistance to chemotherapy-mediated apoptotic cell death than fascin-negative counterparts. This increased chemoresistance was at least partially mediated through PI3K/Akt signalling, and was paralleled by increased FAK phosphorylation, enhanced expression of the inhibitor of apoptosis proteins (XIAP and Livin) and suppression of the proapoptotic markers (caspase 9, caspase 3 and PARP). CONCLUSIONS: This is the first report to demonstrate fascin involvement in breast cancer chemotherapeutic resistance, supporting the development of fascin-targeting drugs for better treatment of chemoresistance breast cancer.

Classification of benign fatty tumours of the upper limb.

In this paper, the authors offer a classification of benign fatty tumours of the upper limb. There are three histologically distinct types of fat cells: immature fat cells which give rise to lipoblastomas, mature brown fat cells which give rise to hibernomas and mature white fat cells which give rise to lipomas. Lipomas are the most common and they are sub-classified according to the anatomic site of fat cells into dermal, subcutaneous and sub-fascial lipomas; or tumours directly related to muscle, bone, synovium or nerve. Finally, the authors review 67 patients with benign fatty tumours of the upper limb and provide clinical examples of these tumours including their characteristic histological and radiological features.

Fine-needle aspiration of the testis in azoospermic men: the value of measuring serum follicle stimulating hormone and testicular size.

Testicular fine-needle aspiration biopsy (FNAB) is used as a primary tool in assessing azoospermic infertile men in our institution. If the FNA is negative for sperm, a subsequent testicular biopsy specimen and wet preparation are obtained with possible immediate fertilization. To our knowledge, the value of these techniques in the context of testicular size and serum levels of follicle stimulating hormone (FSH) has not been explored. We reviewed 453 FNA biopsies of the testis performed for the identification of sperm in infertile azoospermic males between 1999 and 2000. We identified cases that had all three procedures (FNA, wet preparation and biopsy) performed. These were the patients that were compared for testicular size using Seager orchiometry and serum levels of FSH. Of the 453 FNAs reviewed, 128 (21%) had all three procedures performed. Seventy-two cases (56%) were negative in all three tests, 26 (20%) cases were positive in all tests, and 30 cases (23%) had different results. These 30 cases were excluded. The testicular size in the negative group ranged from 4 to 16 ml (median, 10 ml) and the positive group had testicular sizes ranging from 10 to 25 ml (median, 15 ml; P = 0.0001). The negative group had serum FSH levels ranging from 3 to 52 IU/l (median, 19 IU/l) whereas the positive group had serum levels ranging from 3 to 26 IU/l (median, 10 IU/l; P = 0.0001). Our findings suggest that in infertile azoospermic men, a testicular size of <10 ml combined with a serum FSH level of >19 IU/l, the chances of retrieving sperm are minimal using all three diagnostic modalities. The use of this cutoff point would lead to a 30-50% reduction in the number of procedures performed. This reduction would have a significant impact on the management of these patients with a significant decrease in cost, logistics, and patient anxiety.

Phase II study of neoadjuvant paclitaxel and cisplatin for operable and locally advanced breast cancer: analysis of 126 patients.

In an earlier study, we have demonstrated a high clinical and pathologic response rate of neoadjuvant paclitaxel (P) and cisplatin (C) for patients with locally advanced breast cancer (LABC). The current phase II study includes larger number of patients who had longer follow-up. A total of 126 consecutive patients with noninflammatory LABC (T2 >4 cm, T3 or T4, N0-N3, M0) were included in the study. Patients were scheduled to receive three to four cycles of the neoadjuvant PC (paclitaxel 135 mg m(-2) and cisplatin 75 mg m(-2) on day 1) every 21 days. Patients were then subjected to surgery and subsequently received six cycles of FAC (5-fluorouracil 500 mg m(-2), doxorubicin 50 mg m(-2), and cyclophosphamide 500 mg m(-2)) or four cycles of AC (doxorubicin 60 mg m(-2) and cyclophosphamide 600 mg m(-2)); all drugs were administered intravenously on day 1 with cycles repeated every 21 days. Patients then received radiation therapy, and those with hormone receptor-positive tumours were given adjuvant tamoxifen intended for 5 years. The median age was 41 years. Clinically, 12, 52, and 37% of patients had T2 >4 cm, T3, and T4, respectively. The mean tumour size was 7 cm (95% CI, 7.3-8.5). The clinical nodal status was N0, N1, and N2-N3 in 32, 52, and 17% of patients, respectively. Disease stage at diagnosis was IIA (2%), IIB (32%), IIIA (28%), and IIIB (39%). Clinical assessment of the primary tumour and the axillary nodal status after primary chemotherapy showed that 35 patients (28%) achieved complete response (cCR), while 80 (63%) demonstrated partial response to PC. Of patients with evaluable pathologic data of the primary tumour (123 patients), complete pathologic response (pCR) was achieved in 29 patients (24%), and an additional nine (7%) only had a microinvasive disease. Moreover, 20 of the 122 patients (16%) had no residual disease in the primary tumour or in the axillary nodes. Failure to attain cCR predicted failure to achieve pCR. At a median follow-up of 37.5 months (95% CI, 31.5-43.3), 71% were alive with no recurrence, 16% were alive with evidence of disease, and 13% were dead. Of the 122 patients who had surgery, 36 (29%) developed recurrence including one of the patients who attained pCR. The median overall or disease-free survival has not been reached with a projected 5-year overall survival (OS) and disease-free survival (DFS) of 85% (+/-4%) and 63% (+/-5%), respectively. On multivariate analysis, clinical response of the primary tumour, pathological response of the primary tumour, and the pathological nodal status were identified as independent prognostic variables for DFS. No variable, however, was identified to prognosticate OS. PC was acceptably safe. Neoadjuvant PC as used in this phase II study in a multidisciplinary strategy was highly effective. Clinical and pathologic responses remain the most important variables that predict outcome.

Primary diagnosis and REAL/WHO classification of non-Hodgkin's lymphoma by fine-needle aspiration: cytomorphologic and immunophenotypic approach.

The Revised European American lymphoma (REAL) and World Health Organization (WHO) classification of non-Hodgkin's lymphoma (NHL) relies on the constellation of cytologic, phenotypic, genotypic, and clinical characteristics of NHL. For the most part, the classification does not rely on architectural pattern for classification of neoplasms. This classification makes it possible to diagnose and classify lymphomas by fine-needle aspiration (FNA). In this study, we attempted to evaluate the accuracy of FNA in diagnosing and classifying NHL within the context of the REAL/WHO classifications. Cases included only those in which FNA was the primary diagnosis, followed by a surgical biopsy for confirmation. Flow cytometry (FCM) for phenotyping was carried out whenever material was available. Two groups of pathologists were identified. Group A consisted of pathologists with background training in cytopathology and/or hematopathology (three pathologists). Group B consisted of experienced surgical pathologists with no training in cytopathology and/or hematopathology (four pathologists). Seventy-four cases were included in the study. FCM phenotyping was performed in 53 cases (71%). Large cell lymphoma constituted 63% of the cases. The remaining lymphomas included Burkitt's, small lymphocytic, lymphoblastic, follicle center cell, Ki-1, mantle cell, marginal zone, and natural killer cell lymphoma. The diagnosis of lymphoma was rendered for all cases. The correct classification was seen in 63% of the cases. Classification was more accurate in immunophenotyped than in nonimmunophenotyped cases (84% vs 33%; P = 0.00004). Group A pathologists showed higher incidence of proper classification than group B (80% vs 56%; P = 0.046). The diagnosis and classification of NHL can be achieved in a large number of cases on FNA material. This accuracy can be increased if cytomorphologic criteria are established for different entities of NHL aided by FCM for phenotyping.

F-18 FDG positron emission tomography in primary breast non-Hodgkin's lymphoma.

A 50-year-old woman had an irregular, mobile, firm right breast mass that became progressively larger in the past 3 months that measured 18 x 15 cm at the time of examination. She had no nipple discharge or skin changes. A 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) showed a ring-shaped breast uptake consisting of high peripheral glycolytic activity and a cold center most likely representing necrosis or hemorrhage despite the absence of a history of trauma, surgical intervention, chemotherapy, or radiation to the breast. Whole-body images did not show any evidence of lymph node involvement or distant metastases. These results were confirmed by computed tomography of the chest, abdomen, and pelvis. Cytologic examination of a fine-needle aspiration of the breast mass showed diffuse large B-cell, intermediate grade, non-Hodgkin's lymphoma. Although it occurs infrequently, primary breast lymphoma should be considered in patients with a breast mass that shows a ring-shaped FDG uptake. A PET scan, in contrast to other imagining techniques, offers the advantage of screening the entire body, excluding the presence of metastases, and confirming the primary origin of the breast lymphoma.

High complete pathological response in locally advanced breast cancer using paclitaxel and cisplatin.

BACKGROUND: In an earlier study, we have demonstrated a high response rate in metastatic breast cancer using paclitaxel (P) and cisplatin (C). A phase II study using the same regimen (PC) has been conducted in locally advanced breast cancer (LABC). METHODS: A total of 72 consecutive patients with non-inflammatory LABC (T2 > or = 4 cm, T3 or T4, N0-N2, M0). Patients were scheduled to receive 3-4 cycles of the neoadjuvant PC (paclitaxel 135 mg/m2 and cisplatin 75 mg/m2 on day 1) every 21 days. Patients were then subjected to surgery and subsequently received 6 cycles of FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) or 4 cycles of AC (doxorubicin 60 mg/m2, and cyclophosphamide 600 mg/m2). Patients then received radiation therapy, and those with hormone receptor positive tumors were given adjuvant tamoxifen intended for 5 years. RESULTS: The median age was 39 years (range, 24-78). Clinically, 7%, 58%, and 35% of patients had T2 > or = 4 cm, T3, and T4, respectively. Disease stage at diagnosis was IIB (33%), IIIA (27%), and IIIB (40%). Complete and partial clinical response to PC was demonstrated in 13 (18%), and 52 (72%) patients, respectively. Of those patients with evaluable pathologic response (68 patients), complete pathologic response (pCR) was achieved in 15 (22%) patients. At a median follow-up of 22 (+/- 3.5) months, 58 (81%) were alive with no recurrence, nine (12%) were alive with evidence of disease, and five (7%) were dead. None of the patients achieving pCR has developed any relapse. The median overall survival has not been reached for all 72 patients with a projected 3-year survival (+/- SE) of 90% (+/- 4%). The median progression-free survival (PFS) was 42.1 (+/- 4.8) months with a projected PFS of 74% +/- 7% at 3-years (for 68 patients). CONCLUSIONS: PC regimen in LABC produced a high pCR. The contribution of the other added modalities to survival could not be assessed.

Accuracy of cytologic diagnoses made from touch imprints of image-guided needle biopsy specimens of nonpalpable breast abnormalities.

We investigated the diagnostic utility and accuracy of touch imprints (TIs) prepared from core-needle biopsy (CNB) specimens of nonpalpable breast abnormalities. We reviewed air-dried, Diff-Quik-stained TIs prepared from 172 consecutive CNB specimens obtained with stereotactic or sonographic guidance. Using criteria established for fine-needle aspirates, TIs were categorized as benign, atypical, suspicious, malignant, or unsatisfactory (i.e., showing fewer than six benign epithelial cell clusters or cell distortion). Cytologic diagnoses of TIs were then correlated with the histologic diagnoses of corresponding CNB specimens. CNB specimens were histologically diagnosed as carcinoma (102 cases), benign (59 cases), low-grade phyllode tumor (six cases), and atypical ductal hyperplasia (five cases). TIs were cytologically diagnosed as malignant (63 cases), benign (35 cases), suspicious (19 cases), atypical (18 cases), and unsatisfactory (37 cases). Correlation of the cytologic and histologic diagnoses showed that five TIs diagnosed as benign were false-negative results for histologically diagnosed carcinomas (four cases) and phyllodes tumor (one case). False-negative results were attributed to poor representation of malignant cells. Two TIs diagnosed as suspicious were false results for two histologically diagnosed fibroadenomas. The false suspicious findings resulted from TIs with high cellularity, cytologic atypia, or no familiar (i.e., as seen on fine-needle aspirates) smear pattern. Unsatisfactory TIs were noted in both benign (44%) and malignant (11%) CNB specimens. When lesions categorized as suspicious were grouped with the malignant cases and those classified as atypical were grouped with the negative cases, TI sensitivity and specificity, were 83% and 95%, respectively. Fibroadenomas are difficult to identify on TIs and are likely to be misdiagnosed as suspicious. While high- and intermediate-grade carcinomas are easily categorized using TIs, low-grade carcinomas are best categorized as suspicious because of overlapping cytologic features with proliferative breast lesions. Increased experience with cytologic analysis of TIs improves the accuracy of cytologic diagnoses.

ACTH-producing pituitary cancer: experience at the King Faisal Specialist Hospital & Research Centre.

Pituitary gland is an uncommon site of a primary cancer. Of more than 600 cases of pituitary tumors seen at the KFSH&RC between 1975 to 1998 only 3 patients had primary pituitary cancer. We have previously reported a case of pituitary fibrosarcoma arising as a rare complication of external radiotherapy (ERT) for GH-secreting pituitary adenoma (PA) [1]. We report now 2 cases of ACTH-producing primary pituitary carcinoma (ACTH-PPC); their follow-up data provide information on the natural history of this cancer. Patient #1; a 46 year old lady with Cushing's disease (CD) presented with an enlarged right cervical lymph node (LN) 2 years after having undergone a partial hypophysectomy through transsphenoidal surgery (PHYPX/TSS) and ERT for an invasive pituitary tumor. Patient #2; a 26 year old man presented with CD and underwent bilateral adrenalectomy (ADx) and pituitary ERT. Thirty-nine months later he developed Nelson's syndrome and a PHYPX/TSS was performed. Incidentally discovered hepatic metastases in this patient and an excisional biopsy of the LN in patient #1 showed histological features very similar to the pituitary tumor, and they stained strongly positive for ACTH. Perinuclear spherical hyalinized cytoplasmic inclusions were seen in the LN biopsy that corresponded to bundles of type 1 microfilaments (specific for pituitary ACTH-producing cells) seen by electron microscopy. A whole body 18-Fluoro-2-Deoxy-D-Glucose positron emission (FDG-PET) scanning, showed an intense uptake in the neck mass. A trial of octreotide did not change the exceedingly high levels of ACTH in patient #2, further supporting the diagnosis of ACTH-PPC. The clinical course of 102 months prior to his demise showed continued progression of the primary and the metastatic tumor. Patient #1, is alive at 15 months follow-up; hypercortisolemia is controlled using ketoconazole. ACTH-PPC should be entertained in a patient with CD presenting with persistent cervical lymphadenopathy. The clinical course in our patients suggests that the emergence of PC may involve a proliferative continuum from a pre-existing PA to an invasive tumor, culminating in a carcinoma. Adjunctive events such as ERT/ADx may predispose to the evolution of PC in genetically susceptible individuals. Because ERT is an effective treatment for PA its use will continue; it is important to be aware of the possible complication of primary pituitary carcinoma.

Epstein-Barr virus-associated leiomyosarcoma of the thyroid in a child with congenital immunodeficiency: a case report.

We report an unusual case of multifocal leiomyosarcoma involving the thyroid gland, liver, and right lung in a child with congenital immunodeficiency disease. The smooth muscle nature of these neoplasms was confirmed by immunohistochemistry and electron microscopic studies. In situ hybridization showed large amounts of Epstein-Barr virus messenger RNA within the tumor cells. Although Epstein-Barr virus-associated smooth muscle tumors have been reported in children with AIDS and after organ transplantation, we are unaware of any case report in congenital immunodeficiency disease.

F-18 FDG whole-body positron emission tomography scan in primary breast sarcoma.

Three patients with primary breast sarcoma showed intense F-18 FDG breast uptake on the whole-body scan. In two patients the uptake was irregular and associated with cold foci that corresponded to hypodense lesions noted on the chest CT; these represented areas of pathologically demonstrated tumor necrosis. There was also intense FDG uptake in pulmonary, axillary, and supraclavicular lymph node metastases. All lesions were confirmed by CT scan of the chest. Thus F-18 FDG positron emission tomographic scanning accurately staged the tumors in these two patients, and it documented local recurrence in the third patient. Histopathologic examination showed evidence of a high-grade sarcoma, a primary rhabdomyosarcoma, and a malignant cystosarcoma phyllodes of the breast. Similar to breast carcinoma, F-18 FDG whole-body positron emission tomographic imaging could be useful in diagnosing and staging primary breast sarcomas.

Metastatic transitional cell carcinoma of the ovary from superficial bladder tumour.

A 60-year-old female underwent transurethral resection of superficial grade 2 transitional cell carcinoma (TCC) of the urinary bladder. Six months later, intravesical Mitomycin C instillation was given following two superficial recurrences. A further recurrence of TCC grade I was resected transurethrally 39 months later. Forty-eight months after the original diagnosis the patient developed an abdominal mass, which turned out to be TCC grade 3 involving the left ovary. She underwent laparotomy which showed a left ovarian mass. Total abdominal hysterectomy, bilateral oophorectomy and partial omentectomy were carried out. She developed pelvic metastases 3 months later and died.

Cerebral manifestation of Erdheim-Chester disease: clinical and radiologic findings.

A 33-year-old woman presented with a 3-year history of progressive numbness in the hand, cerebellar ataxia, limb weakness, nystagmus, and dysarthria. T2-weighted MRI revealed abnormal foci of increased signal intensity mimicking demyelinating plaques in the periventricular white matter, and brain 18FDG-PET scan showed increased uptake in the pons. Biopsy from a tibial lesion showed aggregates of foamy histiocytes in the intertrabecular spaces replacing the bone marrow, characteristic of Erdheim-Chester disease. The patient was treated with craniospinal radiation. After 6 months, the clinical picture was stable and the MRI was unchanged.

Sarcomatoid renal cell carcinoma: the chromophobe connection.

Eleven cases of sarcomatoid renal cell carcinoma were studied to determine the relative frequency of various subtypes of renal cell carcinoma that may be associated with sarcomatoid transformation. The epithelial components in these tumors were subcategorized according to established histologic criteria into chromophobe carcinoma (n = 6 cases), clear cell carcinoma (n = 3), papillary carcinoma (n = 1), and indeterminate (n = 1). In nine cases, material was available for immunohistochemical and DNA ploidy studies. The sarcomatoid component in all cases showed positivity for epithelial membrane antigen cytokeratin, indicating an epithelial derivation of these cells. Staining for mesenchymal markers was mostly negative, except for vimentin, which reacted strongly in all cases. DNA ploidy studies using flow cytometry and cell image analysis provided very similar results. Five of five chromophobe sarcomatoid carcinomas showed hypodiploid cell lines in the epithelial areas, whereas the sarcomatoid components mostly showed aneuploid peaks. In the remaining cases, DNA ploidy pattern was more variable. These findings indicate that chromophobe carcinoma may be the most frequent epithelial component associated with sarcomatoid renal cell carcinoma.