Excellent response to gemcitabine in a massively pre-treated woman with extensive cutaneous involvement after recurrence of breast cancer.

A 50-year-old woman presented with local relapse of breast cancer 6 years after partial mastectomy. Relapse was accompanied by extended skin induration due to tumor cell embolization of dermal lymphatics. During the following years the patient was exposed to 11 different anti-tumor regimens including 13 cytotoxic drugs (including alkylating agents, antitumor antibiotics, vinca alcaloids, epipodophyllotoxins, and taxanes), 4 anti-hormonal, and 2 immunologic attempts. Paclitaxel achieved a prolonged local improvement for some 7 months, but further various treatments were ineffective. At that time gemcitabine therapy was initiated and tumor infiltration of the skin was visibly diminished only 2 weeks later. After that tumor regressed further for 5 months and remained stable with continued doses of gemcitabine during much of the woman's last year. The patient died of acute myeloid leukemia (AML) 4 years after the local recurrence of breast cancer. Since multiple treatments using a plethora of aggressive cytotoxic drugs may render several classes of chemotherapy agents ineffective due to cross-resistance, it seems advisable to select mild agents that are not subject to multidrug resistance mechanisms and display a unique mode of action as demonstrated in this case by gemcitabine.

Breast cancer after augmentation mammoplasty.

BACKGROUND: It is thought that implants interfere with breast cancer diagnosis and that cancers in women who have had breast augmentation carry a worse prognosis. METHODS: A prospective breast cancer database was reviewed, comparing augmented and nonaugmented patients for details of histology, palpability, tumor size, nodal status, mammographic status, receptor status, nuclear grade, stage, and outcome. RESULTS: Ninety-nine cancers in augmented women and 2857 cancers in nonaugmented women were identified. Among these women, mammography was normal in 43% of those who had had augmentation and in 5% of those who had not. Augmented women were more likely to have palpable cancers (83% vs. 59%) and nodal involvement (48% vs. 36%), and less likely to have ductal carcinoma in situ (DCIS) (18% vs. 28%). When comparing only women younger than 50, the differences in invasiveness and nodal status lost significance. Cancers diagnosed in the 1990s were more likely to be nonpalpable and noninvasive than those diagnosed in the 1980s. This trend was more pronounced in the augmented population. CONCLUSIONS: Augmented patients were more likely to have palpable cancers, although the overall stage and outcome were similar to those of nonaugmented women. Although there have been significant improvements in our ability to diagnose early breast cancer over the past two decades, mammography continues to be suboptimal in augmented women.

Intravesical and intravenous therapy of human bladder cancer by the herpes vector G207.

G207, a conditionally replicating herpes vector, efficiently kills human bladder cancer cells in vitro. To evaluate the therapeutic potential of G207, we have established three in vivo models similar to the clinical situation. In vivo, G207 was intraneoplastically, intravesically, or intravenously inoculated in nude mice. Intraneoplastic inoculation into subcutaneous tumor caused significant tumor growth inhibition. Intravesical inoculation of G207 also caused decreased tumor growth in an orthotopic human bladder cancer model. Furthermore, multiple intravenous inoculation markedly inhibited subcutaneous tumor growth. These results suggest that intravesical therapy with G207 is effective for localized bladder tumor, especially for carcinoma in situ (CIS), and intravenous therapy with G207 is promising for invasive or metastasized bladder tumor.

Immunohistochemistry on cell blocks from fine-needle cytopunctures of primary breast carcinomas and lymph node metastases.

We assessed the reliability of prognostic biologic markers by means of immunohistochemistry on cell blocks obtained from diagnostic fine-needle cytopunctures of breast carcinomas and their lymph node metastases. Immunohistochemical studies of MIB-1 (Ki-67), estrogen receptors (ER), progesterone receptors (PR), p53, and c-erb-B-2 were performed in 55 cases of primary breast carcinoma on cell blocks (cytoblock technique) and on their corresponding tissue samples (46 mastectomy specimens and 9 Trucut biopsies) and in 38 cases on cell blocks from fine-needle cytopunctures of both the primary breast tumors and their concurrent lymph node metastases. Interobserver reproducibility ranged from 87 to 100%, depending on the marker. A good correlation was observed between immunostaining assessment on cell blocks and on the corresponding tumor tissues as follows: Ki-67 (85%), ER (96%), PR (82%), p53 (76%), and c-erb-B-2 (84%). An excellent correlation was observed between cell-block results for primary tumors and node metastases; however, a far higher percentage of Ki-67-positive nuclei was observed in the nodes than in the corresponding tumors in seven cases. All nodes corresponding to ER- or PR-negative tumors were also negative, whereas the nodes corresponding to two ER-positive and one PR-positive tumor were negative. Marked discrepancies were also noted with p53 in two cases and with c-erb-B-2 in two cases. Most discrepancies occurred with Trucut biopsies and with breast tumors that contained a large intraductal component. We conclude that cell blocks prepared from fine-needle cytopuncture specimens of breast carcinomas and their node metastases are useful when planning neoadjuvant treatment.

Breast carcinoma presenting during or shortly after pregnancy and lactation.

CONTEXT: Much has been written about the clinical management and prognosis of breast carcinomas presenting during pregnancy and lactation, yet little is known about the detailed histopathology of these tumors. OBJECTIVE: To determine whether these carcinomas have any specific diagnostic features. DESIGN: A detailed histologic and immunohistochemical study of 14 cases of breast carcinoma presenting during or shortly after pregnancy or lactation was conducted. The findings were compared with a control group of 13 tumors developing in age-matched women with no recent history of pregnancy or lactation. SETTING: The histopathology department of a tertiary referral teaching hospital. RESULTS: Tumors in the pregnancy/lactation group had a significantly higher incidence of cancerization of lobules (79% vs 15%) and of grade III invasive ductal carcinomas (80% vs 33%). Tumors occurring during lactation were either totally or partly mucinous and were MUC2 positive. Tumors occurring during pregnancy, but not during lactation, were mostly estrogen and progesterone receptor negative (4/5 and 5/5, respectively). All tumors occurring during pregnancy and lactation that were tested for c-erbB-2 overexpression were negative, whereas all 4 tumors tested that occurred shortly after delivery or cessation of lactation were positive for c-erbB-2 overexpression. The incidence of axillary lymph node metastasis was high in both the study and control groups, although it was slightly higher in the control group (78% and 90%, respectively). CONCLUSIONS: Although breast carcinomas diagnosed during or shortly after pregnancy and lactation have features in common with those developing in women of similar ages, particularly with respect to a high incidence of lymph node metastasis, the findings of this study suggest that they may also have distinct morphologic and immunohistochemical features of their own. Such features may vary according to whether the patient was pregnant, lactating, or had recently terminated her pregnancy or lactation at the time of surgical excision. Examination of more cases would help confirm these findings.

Axillary dissection and ductal carcinoma in situ of the breast: a change in practice.

BACKGROUND: Axillary dissection may be associated with significant morbidity and, while it is necessary in the treatment of invasive breast cancer, is not indicated for the treatment of pure ductal carcinoma in situ (DCIS), although it is being performed in a significant number of cases. The present study examined the incidence of elective axillary dissection in the treatment of DCIS cases detected in a mammographic screening programme over a 4-year period, and whether surgeons have changed their practice in this respect. METHODS: BreastScreen Victoria records were examined retrospectively for the period from January 1995 to December 1998 to identify patients treated for DCIS. The incidence and indications for axillary surgery were investigated. RESULTS: There were 579 cases of DCIS and 93 (16%) had some form of axillary surgery, which was thought to be inappropriate in 57 (10%), the latter being performed by 21 city surgeons and 20 rural surgeons. Before surgery, 36 (63%) cases were diagnosed by core biopsy or excision, and 21 (37%) had imaging and cytology alone for diagnosis. The rate of unnecessary axillary dissections dropped steadily from 14% in 1995 to 4% in 1998, a significant reduction (P = 0.01). CONCLUSION: The incidence of axillary dissection for DCIS has dropped significantly over the last 4 years in Victoria, possibly due to increased awareness through education and guidelines. Surgeons are now more aware that in situ lesions do not need axillary dissection, and that axillary dissection should not be performed for breast cancer unless invasion has been proved histologically.

Ductal carcinoma in situ of the breast.

Ductal carcinoma in situ of the breast is a heterogeneous group of lesions with diverse malignant potential. It is the most rapidly growing subgroup in the breast cancer family; it is projected that more than 39,000 new cases will be diagnosed in the United States during 1999. Most new cases are nonpalpable and are discovered mammographically. Treatment is controversial and ranges from excision only, to excision with radiation therapy, to mastectomy. Genetic changes routinely precede morphologic evidence of malignant transformation. Medicine must learn how to recognize these genetic changes, exploit them, and in the future, prevent them.

Microinvasive breast carcinoma: clinicopathologic analysis of a single institution experience.

BACKGROUND: Microinvasive breast carcinoma (MIC) has a good prognosis but specific definitions have varied in the past, making the clinical significance of MIC a subject of debate. METHODS: Microscopic slides of 59 cases of breast carcinoma originally diagnosed as MIC were reviewed retrospectively. Histologic parameters were correlated with clinical findings and outcome to define diagnostic criteria better. RESULTS: On review, the 59 cases were recategorized as follows: pure DCIS (N = 16), DCIS with foci equivocal for microinvasion (N = 7), DCIS with > or =1 focus of microinvasion (N = 11), T1 invasive carcinomas with > or =90% DCIS (N = 18), and T1 tumors with <90% DCIS (N = 7). The MIC cases in the current study averaged 3 separate foci of early infiltration outside the basement membrane, each one not >1.0 mm. The mean follow-up was 95 months. Six patients (10%) had only local recurrence: 1 case each in patients with equivocal microinvasion, microinvasion, and T1 tumors with <90% DCIS and 3 cases among the patients with T1 tumors with > or = 90% DCIS. Four patients, all with T1 tumors with > or =90% DCIS, had distant failure (7%). In the MIC group, only one patient developed a local recurrence after breast conservation. No patient had axillary lymph node metastasis. For the entire series, factors associated with local recurrence were younger age, breast conservation versus mastectomy, and close surgical margins. The only factor associated with distant failure was the size of the DCIS component. Seven patients with T1 tumors with > or =90% DCIS experienced local or distant failure and 5 of these (71%) developed progressive disease or died of disease. All other patients who developed a recurrence were disease free at last follow-up. In a retrospective series, poorer outcome in carcinomas with > or =90% DCIS may be related to the greater likelihood of missed larger areas of invasive carcinoma. Therefore, meticulous and extensive sampling of these carcinomas is required. CONCLUSIONS: MIC as defined has a good prognosis. It has a different biology than T1 invasive carcinoma with > or =90% DCIS, which may progress and cause death. Large tumors with multiple foci of microinvasion may have metastatic potential.

Sentinel node biopsy in ductal carcinoma in situ patients.

BACKGROUND: Sentinel lymph node (SLN) mapping is an effective and accurate method of evaluating the regional lymph nodes in breast cancer patients. The SLN is the first node that receives lymphatic drainage from the primary tumor. Patients with micrometastatic disease, previously undetected by routine hematoxylin and eosin (H&E) stains, are now being detected with the new technology of SLN biopsy, followed by a more detailed examination of the SLN that includes serial sectioning and cytokeratin immunohistochemical (CK IHC) staining of the nodes. METHODS: At Moffitt Cancer Center, 87 patients with newly diagnosed pure ductal carcinoma in situ (DCIS) lesions were evaluated by using CK IHC staining of the SLN. Patients with any focus of microinvasive disease, detected on diagnostic breast biopsy by routine H&E, were excluded from this study. DCIS patients, with biopsy-proven in situ tumor by routine H&E stains, underwent intraoperative lymphatic mapping, using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised SLNs were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. All SLNs that had only CK-positive cells were subsequently confirmed malignant by a more detailed histological examination of the nodes. RESULTS: CK IHC staining was performed on 177 SLNs in 87 DCIS breast cancer patients. Five of the 87 DCIS patients (6%) had positive SLNs. Three of these patients were only CK positive and two were both H&E and CK positive. Therefore, routine H&E staining missed microinvasive disease in three of five DCIS patients with positive SLNs. In addition, DCIS patients with occult micrometastatic disease to the SLN underwent a complete axillary lymph node dissection, and the SLNs were the only nodes found to have metastatic disease. Of interest, four of the five node-positive patients had comedo carcinoma associated with the DCIS lesion, and one patient had a large 9.5-cm low grade cribriform and micropapillary type of DCIS. CONCLUSIONS: This study confirms that lymphatic mapping in breast cancer patients with DCIS lesions is a technically feasible and a highly accurate method of staging patients with undetected micrometastatic disease to the regional lymphatic basin. This procedure can be performed with minimal morbidity, because only one or two SLNs, which are at highest risk for containing metastatic disease, are removed. This allows the pathologist to examine the one or two lymph nodes with greater detail by using serial sectioning and CK IHC staining of the SLNs. Because most patients with DCIS lesions detected by routine H&E stains do not have regional lymph node metastases, these patients can safely avoid the complications associated with a complete axillary lymph node dissection and systemic chemotherapy. However, DCIS patients with occult micrometastases of the regional lymphatic basin can be staged with higher accuracy and treated in a more selective fashion.

Biopsy method and excision volume do not affect success rate of subsequent sentinel lymph node dissection in breast cancer.

INTRODUCTION: Sentinel lymph node dissection (SLND) is becoming a recognized technique for accurately staging patients with breast cancer. Its success in patients with large tumors or prior excisions has been questioned. The purpose of this study was to evaluate the effect of biopsy method, excision volume, interval from biopsy to SLND, tumor size, and tumor location on SLND success rate. METHODS: Consecutive patients who underwent SLND followed by completion axillary lymph node dissection from October 1991 to December 1995 were analyzed. Included were cases performed early in the series before the technique was adequately developed. Excision volume was derived from the product of three dimensions as measured by the pathologist. Two end points were analyzed: sentinel node identification rate and accuracy of SLND in predicting axillary status. Univariate analyses using chi2 or Fisher's exact test for categorical variables and Wilcoxon rank sums for continuous variables were performed. Multivariate analysis was performed using logistic regression. RESULTS: There were 284 SLND procedures performed on 283 patients. Median age was 55 years. The most recent biopsy method used before SLND was stereotactic core biopsy in 41 (14%), fine-needle aspiration in 62 (22%), and excision in 181 (64%) procedures. The mean excision volume was 32 ml with a range of 0.3-169 ml. The mean time from biopsy to SLND was 17 days with a range of 0-140 days. The mean tumor size was 2.0 cm (15 Tis [5%], 184 T1 [65%], 72 T2 [25%], and 13 T3 [5%]). Tumors were located in the outer quadrants in 74%, the inner quadrants in 18%, and subareolar region in 8%. The sentinel node was identified in 81%, and 39% had metastases. There were three false-negative cases early in the series. Sensitivity was 97%, and accuracy was 99%. Negative predictive value was 98% in cases in which the sentinel node was identified. On the basis of biopsy method, excisional volume, time from biopsy to SLND, tumor size, and tumor location, there was no statistically significant difference (P>.05) in sentinel node identification rate or accuracy of SLND. CONCLUSIONS: SLND has a high success rate in breast cancer patients regardless of the biopsy method or the excision volume removed before SLND. In addition, the interval from biopsy to SLND, tumor size, and tumor location have no effect on the success rate of SLND, even in this series which included patients operated on before the technique was adequately defined. Patients with breast cancers located in any quadrant and diagnosed either with a needle or excisional biopsy could be evaluated for trials of SLND.

In squamous cell carcinoma of the vulva, overexpression of p53 is a late event and neither p53 nor mdm2 expression is a useful marker to predict lymph node metastases.

To offer more tailored treatment to individual patients with squamous cell carcinoma of the vulva, more accurate prediction of lymph node metastases is required. As p53 and mdm2 are genes known to be involved in the development of other tumours, we studied expression of p53 and mdm2 in carcinogenesis of squamous cell carcinoma of the vulva and their clinical relevance. Archival material of 141 T1 and T2 vulvar tumours were used. Of the 141 primary tumours, the corresponding 39 lymph node metastases (LNM) were studied, and in 90 cases the pre-existent epithelia adjacent to the tumour (EAT) and in 14 cases vulvar intraepithelial neoplasia adjacent to the tumour (VIN) was also investigated. Detection of p53 and mdm2 protein was immunohistochemically performed. Scoring categories were: negative (1); weakly positive (2); moderately to markedly positive (3); and markedly positive (4). Overexpression of p53 was seen in 56% of the LNM, 39% of the primary tumours, 21% of the VIN lesions and 0% in the group of EAT. No relation was found between overexpression of p53 in the primary tumour and LNM. Expression of mdm2 was seen in 14% of the primary tumours, of which four cases were marked positive. In the group of LNM no mdm2-positive staining was observed. In the group of EAT, 25% was mdm2-positive, of which six cases were marked positive. In the group of VIN, 36% showed moderate (score 3) mdm2 expression. No relation was found between expression of mdm2 and LNM. In squamous cell carcinoma, overexpression of p53 is a late event in carcinogenesis. Marked expression of mdm2 is rarely seen in vulvar carcinomas, indicating that aberrant p53 cannot induce mdm2 expression. LNM cannot be predicted by detection of these proteins.

[Recurrence of bladder cancer in fossa navicularis 12 years after total cystectomy: a case report].

We report a case of urothelial cancer recurrence in fossa navicularis of urethra 12 years after total cystourethrectomy for bladder cancer. A 73-year-old man had undergone total cystourethrectomy and ureterocutancostomy for multiple bladder cancer on June 13, 1986. Histopathological findings showed transitional cell carcinoma, G3, pT4 with carcinoma in situ. Twelve years after the cystectomy, he was admitted to our hospital complaining of the induration of the glans penis. Magnetic resonance imaging showed a high intensity tumor in T1-WI and low intensity tumor in T2-WI, which had invaded fossa navicularis of urethra to glans penis. Aspiration biopsy of the penile tumor revealed transitional cell carcinoma. Therefore, we performed partial penectomy on July 16, 1998, since computed tomography showed no lymph node swelling in the inguinal region. Five months after the second operation, he was diagnosed with bilateral inguinal lymph node metastasis. Then we performed 2-course M-VAC (methotrexate, vinblastine, doxorubicin cisplatin) therapy, which showed partial response. Thereafter, bilateral inguinal lymphadenectomy with one-course postoperative M-VAC therapy was performed.

Ductal carcinoma in situ (DCIS) in the male breast: a morphologic study of 84 cases of pure DCIS and 30 cases of DCIS associated with invasive carcinoma--a preliminary report.

BACKGROUND: Ductal carcinoma in situ (DCIS) in the male breast is a rare disease that to the authors' knowledge has been investigated to date only in small numbers. Compared with DCIS in the female breast, distinct clinical and morphologic differences have been suggested. METHODS: The files of the Armed Forces Institute of Pathology (AFIP) were searched for cases of pure DCIS and DCIS associated with invasive carcinoma (DCISAIC) in male patients. A total of 280 cases of pure DCIS and 759 invasive mammary tumors were identified; 114 cases (including 84 pure DCIS and 30 DCISAIC) were studied for this preliminary report. All cases were reviewed and classified according to specific subtypes (papillary, cribriform, solid, micropapillary, and comedo) and grades of DCIS. Basic clinical data were extracted from the patients' charts. RESULTS: Men with pure DCIS presented at a median age of 65 years, with a typically nodular, retroareolar, partially cystic mass that frequently was associated with a nipple discharge. The median duration of symptoms was 2 months for patients with pure DCIS and 6 months for patients with DCISAIC. Histologically, the predominant appearance of DCIS (in 74% of cases) was that of a papillary carcinoma often with a superimposed cribriform pattern. Intraductal extension beyond the main papillary lesion was common. It is interesting to note that the pure DCIS cases in this series were uniformly of either low or intermediate grade; high grade or comedocarcinomas were only observed within the group of DCISAIC. No significant morphologic differences between pure DCIS and DCISAIC were encountered, although DCISAIC did show relatively more cellular atypia with more frequent necrosis compared with pure DCIS. CONCLUSIONS: DCIS in the male breast is a distinct lesion that occurs at an older age and displays a significantly different distribution of morphologic subtypes compared with its female counterpart. It presents most frequently as an intraductal papillary carcinoma, and less commonly as a nonpapillary cribriform, solid, or micropapillary DCIS. In the current study the majority of pure DCIS cases were low grade (AFIP Grade 1) with occasional cases displaying necrosis (AFIP Grade 2); high grade pure DCIS appears to be a rare lesion in the male breast. In contrast, DCIS associated with invasive carcinoma more frequently is of higher grade.

Intraoperative localization of the sentinel node in breast cancer: technical aspects of lymphoscintigraphic methods.

Axillary lymph node dissection is an important part of the surgical treatment of breast cancer as a staging procedure. Recent progressive advances in early detection have led to the treatment of small primary carcinomas; thus, a great number of axillary dissections show completely negative lymph nodes. The sentinel node (SN) concept, developed for melanoma patients, seems to be similarly valid in breast cancer and has the potential to change the standard surgical approach in these patients. To verify the accuracy of lymphoscintigraphic method associated with radioguided biopsy of the sentinel node in a large series of patients, we studied 382 patients with operable breast cancer. Lymphoscintigraphy (LS) was performed the day before surgery; three different-sized ranges of 99mTechnetium-labeled colloid particles were injected either by subdermal or peritumoral administration. Planar scans were registered in anterior and oblique projections, and a cutaneous marker was placed over the skin corresponding to the SN as visualized. SNs were localized and removed during surgery, using a gamma-detecting probe (GDP); total axillary dissection was then performed. In 54 patients, blue dye was also administrated in the tumor bed immediately after excision of the primary. LS identified at least one SN in 377 of 382 cases (98.7%). Axillary SN was localized in 371 cases (97.1%). The overall concordance between SN status and other axillary nodes was 96.8% (359 of 371). Localization of the SN was easier when large-size particles of colloidal albumin were injected in a volume of 0.4 ml. GDP successfully localized SN in 54/54 cases (100%), while blue dye identified SN in 37/54 patients (68.5%). In 33 of 37 cases (89%) the dye and LS identified the same node. LS and GDP-guided surgery provide accurate identification and removal of the SN, particularly when large-size radiolabeled colloids are injected in a small volume.

Vulvar squamous cell carcinoma metastatic to the skin.

BACKGROUND: Cutaneous metastases from vulvar squamous cell carcinomas (SCC) have been reported only twice previously and both patients expired shortly after they occurred. Mohs surgery has been reported in three previous publications as a successful treatment for local invasive vulvar SCC and Bowen's disease. OBJECTIVE: To describe a third case with cutaneous metastases and 14 other cases of invasive and in situ vulvar SCC treated by fresh tissue Mohs surgery in a pilot study at the University of Wisconsin between 1976 and 1995. METHODS: We took photographs of the gross appearance and of the histologic slides of the tumor at the local site and at the metastatic sites on the skin and reviewed patients' charts. RESULTS: One patient developed pelvic and cutaneous metastases 5 years after radical vulvectomy with bilateral node dissection. She expired shortly after the skin metastases appeared. The courses of the patients followed after Mohs surgery for vulvar SCC were variable. CONCLUSIONS: Cutaneous metastases from vulvar SCC are rare but carry a grim prognosis. Mohs surgery should be considered in select cases to try to prevent excess morbidity and mortality.

Optic nerve breast metastasis mimicking meningioma.

PURPOSE: We report on an optic nerve breast metastasis masquerading initially as a central retinal vein occlusion and later as an optic nerve meningioma. METHODS: A 60-year-old female presented with a left central retinal vein occlusion (CRVO). She represented 7 months later with left upper ptosis, proptosis and painful rubeotic glaucoma Computed tomography (CT) and magnetic resonance imaging suggested an optic nerve meningioma. On referral to the regional orbital unit a mild left external ophthalmoplegia was noted and, in view of previous right mastectomy and chemotherapy 3 years earlier, the left optic nerve was biopsied simultaneously with left enucleation of her painful eye. RESULTS: Histopathology showed infiltration of the optic nerve and meningeal sheath spreading into the subretinal space and vitreous by malignant epithelial cells, consistent with breast origin. Further CT imaging and bone scans revealed no other metastases. Single field left orbit radiotherapy of 20 Gy was given in five fractions and Arimidex (Zeneca Pharmaceuticals, Cheshire, England) was commenced with the cessation of tamoxifen. The patient was also given an ocular prosthesis. Sadly, she lost vision in her other eye due to retrograde malignant invasion of her optic chiasm and died 6 weeks later. CONCLUSIONS: Orbital and choroidal metastases are relatively common but isolated optic nerve metastases are extremely rare. Progressive infiltration of the nerve is likely to enhance CRVO ischaemia and resultant rubeotic glaucoma. In the diagnosis of CRVO, proptosis or external ophthalmoplegia, the presence of pre-existing malignant disease should raise concerns, as delay in diagnosis may affect outcome, particularly if the metastases are sensitive to pharmacological therapy.

The significance of keratinizing squamous cell histology in Chinese patients with nasopharyngeal carcinoma.

Six hundred and ninety-three Chinese patients with non-metastatic nasopharyngeal carcinoma (NPC) were treated at one institution under a uniform protocol between 1984 and 1989. The tumour histology of these patients was subjected to a standardized review and classified into two distinct groups of World Health Organization (WHO) type I (keratinizing squamous cell carcinoma) (n = 13) or WHO types II and III (non-keratinizing carcinoma and undifferentiated carcinoma) (n = 662). The differentiation between the two groups was uncertain in 18 patients. The patient characteristics and clinical outcome after a uniform treatment policy of the two groups were not statistically significantly different. The low incidence of WHO type I NPC may account for the lack of prognostic significance of this histological subtype in Chinese populations.

Loss of heterozygosity at chromosome 9p in ductal carcinoma in situ and invasive carcinoma of the breast.

Twenty-three cases of ductal carcinoma in situ (DCIS), ten of which had an associated invasive component, were studied for loss of heterozygosity (LOH) of microsatellite markers on chromosome 9p and the results compared with a panel of 20 invasive breast carcinomas. In addition to the gene encoding p16, chromosome 9p is also thought to contain other putative tumour-suppressor genes. If the three panels of breast tumours showed LOH of markers in this region this would suggest that such putative genes were important in breast carcinogenesis. By studying both preinvasive and invasive breast tumours, it should also be possible to gain further information about the relationship between lesions of a different stage and to determine whether DCIS is indeed a precursor of invasive ductal carcinoma. Levels of LOH were low in the invasive-only set of tumours. Surprisingly, considerably higher levels of loss were observed in the tumours with an in situ component. Also, much heterogeneity was observed between different DCIS ducts or invasive tumour and DCIS from the same case.

Skin-sparing mastectomy and immediate reconstruction: oncologic risks and aesthetic results in patients with early-stage breast cancer.

Skin-sparing mastectomy has been advocated as an oncologically safe approach for the management of patients with early-stage breast cancer that minimizes deformity and improves cosmesis through preservation of the skin envelope of the breast. Because chest wall skin is the most frequent site of local failure after mastectomy, concerns have been raised that inadequate skin excision could result in an increased risk of local recurrence. Precise borders of the skin resection have not been well established, and long-term local recurrence rates after skin-sparing mastectomy are not known. The purpose of this study was to evaluate the oncologic safety and aesthetic results for skin-sparing mastectomy and immediate breast reconstruction with a latissimus dorsi myocutaneous flap and saline breast prosthesis. Fifty-one patients with early-stage breast cancer (26 with ductal carcinoma in situ and 25 with invasive carcinoma) undergoing primary mastectomy and immediate reconstruction with a latissimus flap were studied from 1991 through 1994. For 32 consecutive patients, skin-sparing mastectomy was defined as a 5-mm margin of skin designed around the border of the nipple-areolar complex. After the mastectomy, biopsies were obtained from the remaining native skin flap edges. Patients were followed for 44.8 months. Histologic examination of 114 native skin flap biopsy specimens failed to demonstrate breast ducts in the dermis of any of the 32 consecutive patients studied. One of 26 patients with ductal carcinoma in situ had metastases to the skin of the lateral chest wall and back. Four other patients, one with stage I disease and three with stage II-B disease, had recurrent breast carcinoma. The stage I patient had a local recurrence in the subcutaneous tissues near the mastectomy specimen. Two patients suffered axillary relapse, and one had distant metastases to the spine. The findings of this study support the technique of skin-sparing mastectomy as an oncologically safe one, based on an absence of breast ductal epithelium at the margins of the native skin flaps and a local recurrence rate of 2 percent after 45 months of follow-up. Although these results need to be confirmed with greater numbers of patients and longer follow-up, skin-sparing mastectomy and immediate breast reconstruction may be considered an excellent alternative treatment to breast conservation for patients with ductal carcinoma in situ and early-stage invasive breast cancer.

Magnetic resonance imaging in breast cancer staging.

For many solid carcinomas, high-resolution cross-sectional imaging has changed cancer staging, the evaluation of therapeutic response, the detection of recurrence, and even how therapy is selected and performed. Such imaging has not yet had similar effects on breast cancer. Evaluations of therapeutic response in breast carcinomas have been impeded by the current limited methods of evaluating breast tumor size and extent: clinical palpation, ultrasonography, and mammography. The use of magnetic resonance imaging (MRI) of the breast in the evaluation of breast tumors brings the advantages of high-resolution cross-sectional imaging to breast cancer staging and treatment evaluation and is likely to greatly enhance research efforts in this complex disease. MRI of the breast has evolved to be the most accurate noninvasive technique for local staging of breast cancer. MRI is most accurate in measuring tumor size and detecting multicentric disease. These staging characteristics affect the selection of therapy and initial determination of prognosis; therefore, MRI of the breast can change the assessment of fundamental parameters on which treatment is selected. Because clinical trials of new cancer treatments are predicated on proper and accurate characterization of the tumor, MRI also should affect how clinical trials are performed and evaluated.