Traumatic panniculitis.

Traumatic panniculitis refers to changes in the subcutaneous fat related to physical or chemical agents. The clinical picture of traumatic panniculitis is nonspecific. Cutaneous lesions are indurated, warm, red, subcutaneous plaques or nodules not necessary related to the intensity of the injury. The histologic picture includes fat microcysts surrounded by histiocytes, collections of foam cells, and inflammatory cells. Late lesions may show fibrosis, lipomembranous changes, or dystrophic calcic deposits. Traumatic panniculitis is usually a self-limiting disorder and requires only symptomatic treatment.

Subcutaneous sarcoidosis.

Subcutaneous sarcoidosis has been reported to occur in 1.4% to 6% of patients with systemic sarcoidosis. Most reported cases are in women, most often in their fifth and sixth decades, and appear as multiple, asymptomatic, hardly indurated subcutaneous nodules without changes in the overlying epidermis. The lesions are characteristically located in the upper extremities, mainly in the forearms, and usually are bilateral and asymmetric. In most cases the lesions appear at the beginning of systemic sarcoidosis and are not associated with chronic fibrotic disease. Histopathologically, sarcoidosis is characterized by noncaseating naked granulomas involving fat lobules, with minimal to no septal involvement.

HER-2/neu status and response to CMF: retrospective study in a series of operable breast cancer treated with primary CMF chemotherapy.

PURPOSE: Primary chemotherapy brings the opportunity for an early and accurate assessment of response and offers an ideal model to search for new predictors of response. HER-2/neu is one of the most studied genes for this purpose. PATIENTS AND METHODS: Her-2/neu was tested in a non-randomized series of 300 patients with operable breast carcinomas treated with primary CMF. Response was assessed by mammography. Disease-free survival (DFS) and overall survival (OS) were calculated after a mean follow-up of 116 months. Statistical analysis was performed to study the association between HER-2/neu status and response to CMF. RESULTS: Overexpression/amplification was found in 23.66% cases. Univariate analysis showed that response was similar in HER-2/neu positive and negative tumors (51.38 vs. 47.36%, P = 0.6). Triple negative tumors (ER, PR and HER-2/neu negative) presented the highest response rate (64.9%). By multivariate analysis, response was significantly correlated to higher nuclear grade and negative estrogen receptor status (P = 0.02 and 0.007, respectively). Patients with HER-2/neu positive tumors presented shorter survival rates (P = 0.06). Patients with response to CMF showed a better survival over non-responders independent of Her-2/neu status. Patients with the combination of response to CMF and Her-2/neu negative tumors presented the best outcome. On the other hand, the association of no response to CMF and positive Her-2/neu score was statistically related to poor DFS and OS. CONCLUSIONS: CMF indication is independent of Her-2/neu status.

Cutaneous infiltration by cancer.

BACKGROUND: Cutaneous infiltration by cancer has been reported to occur in 0.7% to 9% of all patients with malignant neoplasms and is usually considered a late event in the evolution of most visceral carcinomas. OBJECTIVE: To analyze the clinicopathological features of cutaneous infiltration by cancer. METHODS: All biopsy specimens codified as cutaneous infiltration by cancer between 1988 and 2005 were retrieved. Patients with hematologic malignancies were excluded. The clinical charts of the patients were reviewed to obtain additional information. RESULTS: In all, 381 patients (136 male and 245 female) were included in the study. The most frequent primary tumors were breast carcinoma (168 cases), malignant melanoma (59 cases), mucosal carcinoma of the head and neck (34 cases), lung carcinoma (25 cases), and large intestine carcinoma (22 cases). The most frequent clinical presentations were solitary nodule in 153 cases, multiple nodules in 82 cases, and infiltration of surgical scars in 50 cases. In 128 patients (33.6%) the cutaneous infiltrative lesions were present at diagnosis of the primary tumor. The number of yearly specimens of infiltration by breast carcinoma increased significantly from the first half to the second half of the period under examination. LIMITATIONS: This is an observational retrospective study. CONCLUSIONS: With the possibility of determining prognostic factors by analyzing tissue samples from malignant tumors, the role of cutaneous biopsy is expected to become increasingly important in the management of oncology patients, as is already the case with breast carcinoma.

Necrobiosis lipoidica.

Necrobiosis lipoidica (NL) is a granulomatous condition with a degenerative connective tissue of unknown etiology very often associated with diabetes. Histopathologically, NL involves all of the dermis and, often, the subcutaneous fat produces a septal panniculitis. There are some changes suggesting the diagnosis of NL, and systemic disease should be considered if there is the presence of necrotizing vasculitis in the skin biopsy. Many theories of pathogenesis have been proposed, and many types of drugs are available for use in its treatment.

Predictive value of HER-2 and Topoisomerase IIalpha in response to primary doxorubicin in breast cancer.

AIM: To study the predictive role of HER-2 and Topoisomerase IIalpha (TOP2A) in response to primary doxorubicin. METHODS: Two hundred and thirty-two patients with operable breast cancer were treated with doxorubicin prior to surgery. ER, PgR, grade, Ki-67 and HER-2 status were prospectively assessed. HER-2 overexpression was evaluated with immunohistochemistry; positive cases were then studied for gene copy number of HER-2, TOP2A and chromosome 17 centromere by chromogenic in situ hybridisation. Clinical response was assessed by mammography. Pathological response was evaluated as the percentage of tumour replaced by changes due to chemotherapy. RESULTS: HER-2 amplification was associated with clinical response (p=0.04). ER and PgR negativity, high Ki-67 and HER-2 amplification significantly correlated to pathological response (p<0.05). Tumours with coamplification of HER-2 and TOP2A showed a higher percentage of pathological changes (p=0.6). However, in the multivariate analysis for complete pathological response, ER negativity and high Ki-67 index were the only parameters that maintained statistical significance. CONCLUSION: HER2 and Topoisomerase IIalpha amplification failed to show an association with pathological response to doxorubicin, whereas ER negativity and a high proliferation rate were predictive of complete pathological response to this regime.

Cholesterol embolism: still an unrecognized entity with a high mortality rate.

BACKGROUND: Cholesterol embolism (CE) is an increasingly common but often underdiagnosed medical problem. The recognition of clinical manifestations of CE is the first step toward a correct diagnosis. OBJECTIVE: Our aim was to characterize the features of CE and the risk factors for fatal outcome. METHODS: Clinical records of patients with clinical and histopathologic diagnoses of CE seen from January 1993 through March 2003 were reviewed. RESULTS: Twenty-six male patients were identified. Mean age was 64 years (range, 48-88 years). All patients had two or more risk factors for atherosclerosis. All but one patient had preexisting symptomatic atherosclerotic disease. At least one precipitating factor was identified in 23 patients (88%). Diagnosis of CE at admission was made in 9 patients only (35%). Cutaneous lesions (88%) and renal failure (73%) were the most common clinical findings. Complications (dialysis, acute pulmonary edema, amputation, or gastrointestinal surgery) were present in 21 patients (81%), and 15 patients died (58%). Previous chronic renal failure was the only variable associated with mortality (relative risk: 4.54, 95% confidence interval 1.26-16.6; P = .02). LIMITATIONS: The results were obtained from patients admitted to a university hospital. This fact may have selected a higher proportion of severe cases. CONCLUSIONS: CE was frequently misdiagnosed. Skin lesions were the most common clinical findings and skin biopsy provided histologic confirmation in most of the patients. Chronic renal failure was the only factor related to death.

Overproduction of VEGF concomitantly expressed with its receptors promotes growth and survival of melanoma cells through MAPK and PI3K signaling.

Vascular endothelial growth factor (VEGF) is an important mediator of tumor-associated angiogenesis, and consequently it has been associated with metastasis. We report here that the overexpression of VEGF(165) in melanoma xenografts promotes an acceleration of tumor growth and an increase in angiogenesis as well as the spontaneous metastasis formation. In addition, VEGF receptors (VEGFR)1, VEGFR2 and neurophilin-1 are expressed in A375 melanoma cells. Forced overexpression of VEGF in these cells induces cell growth and triggers survival activity in serum-starved cultures, by a mechanism dependent on the mitogen-activating protein kinase signaling pathway. Furthermore, these effects are dependent MEK 1/2 activity. Kinase domain region-specific tyrosine kinase inhibitors dramatically reduced DNA synthesis to 20% with respect to the controls, although they did not completely suppress either the p44 or p42-phosphorylated forms of extracellular signal-regulated protein kinase. These inhibitors also provoked a decrease in Akt phosphorylation. We observed a dramatic reduction in survival after treatment with phosphatidylinositol 3'-kinase (PI3K)-specific inhibitor in the presence of specific tyrosinase inhibitors. We suggest that the overproduction of VEGF(165) concomitantly expressed with its receptors favors cell growth and survival of melanoma cells through MAPK and PI3K signaling pathways. These data support the involvement in melanoma growth and survival of a VEGF-dependent internal autocrine loop mechanism, at least in vitro.

Granuloma faciale: a clinicopathological study of 11 cases.

BACKGROUND: Granuloma faciale is an uncommon disease of unknown etiology that is often misdiagnosed clinically and by general pathologists. OBJECTIVE: To describe the clinicopathological features of a series of patients with granuloma faciale. METHODS: Eleven patients diagnosed with granuloma faciale between 1990 and 2002 were included in the study. RESULTS: Granuloma faciale was diagnosed in 11 patients (9 male and 2 female, mean age 53.45 years). All of them presented facial cutaneous lesions and two of them also developed extrafacial lesions. Histologically, in 8 cases the infiltrate was limited to the upper half of the dermis. Two specimens showed fibrinoid necrosis. Concentric fibrosis around small blood vessels was demonstrated in 5 patients. CONCLUSION: The presence of abundant fibrosis in 5 of our patients similar to that observed in erythema elevatum diutinum suggests that granuloma faciale and erythema elevatum diutinum may be produced by similar or the same pathogenic mechanism.

Primary chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil in operable breast carcinoma.

BACKGROUND: Primary chemotherapy (PC) is becoming an accepted practice to treat large tumors to avoid mastectomies and as a surrogate of outcome. METHODS: A series of 305 patients with tumors >3 cm with T2-3N0-1M0 classification were treated with a multimodal approach that consisted of 3 courses of primary cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) followed by appropriate local treatment and 3 more courses of CMF or 4 courses of doxorubicin. Response was assessed by mammography. RESULTS: The overall response rate was 48% (a 3% pathologic complete response rate). Conservative surgery was achieved in 79.64% of the patients with a low rate of local disease recurrences (5%). Toxicity was minimal. With a median follow-up of 104 months, the 8-year disease-free survival (DFS) rate was 57.63% and the 8-year overall survival (OS) was 67.65%. The DFS and OS rates for patients with a clinical response were significantly longer, i.e., 70% (P=0.0048) and 90% (P=0.0042), respectively. CONCLUSIONS: PC with CMF was feasible. A high rate of breast-conservative surgery was achieved. The current results stressed the value of PC to increase conservative surgery and as a predictor of outcome.

Papular sarcoidosis of the knees: a clue for the diagnosis of erythema nodosum-associated sarcoidosis.

BACKGROUND: In recent years we have systematically explored the skin whenever sarcoidosis was suggested and we have observed with increasing frequency the presence of granulomatous cutaneous lesions of sarcoidosis involving the knees. OBJECTIVE: We sought to evaluate the specific cutaneous lesions of sarcoidosis involving the knees. METHODS: A total of 18 patients with biopsy-proven specific cutaneous sarcoidosis predominantly involving the knees were included in the study. Biopsy specimens were evaluated under polarized light. RESULTS: Of these cases, 4 corresponded to scar-sarcoidosis, 1 to plaque-type sarcoidosis, and 13 were an admixture of papules and minute scars frequently associated with erythema nodosum (papular sarcoidosis of the knees). Foreign particles were observed in 10 of 13 patients with papular sarcoidosis. CONCLUSION: Papular sarcoidosis of the knees can be considered a frequent form of cutaneous sarcoidosis, mainly observed in acute forms of the disease, and frequently associated with erythema nodosum.

Algorithm for the diagnosis of HER-2/neu status in breast-infiltrating carcinomas.

Determination of HER-2/neu overexpression/amplification is becoming increasingly important. The aim of this study is to elaborate an algorithm for the diagnosis of Her-2/neu status in breast-infiltrating carcinomas. Three hundred five breast-infiltrating carcinomas were selected to determine HER-2/neu overexpression by immunohistochemistry with two different methods: the monoclonal antibody CB11 and the HercepTest. Fluorescence in situ hybridization (FISH) was performed in a subgroup of those cases. Time-consuming and reagent costs were calculated for each of the procedures. HER-2/neu overexpression was found in 16% and 33% of the tumors with the monoclonal antibody (mAb) CB11 and with the HercepTest, respectively. There were 50 cases with immunohistochemical discordant results; most of them were HercepTest score 2+/mAb CB11 negative (37/50). Of those cases, only 27% presented gene amplification. The algorithm consisted of testing all the specimens with the mAb CB11 for selection of positive cases, negative cases are confirmed with the HercepTest, and FISH is performed only in those cases with immunohistochemical discordant results. The algorithm rate of HER-2/neu positivity in our series was 22%. Time and costs are reduced by 60% and 41%, respectively, compared to FISH. The use of the algorithm is feasible, accurate, and cost-effective in relation to FISH.

Crohn's disease presenting as prepuce and scrotal edema.

Metastatic cutaneous Crohn's disease, in which noncaseating granuloma infiltration of the skin occurs at sites separated from the gastrointestinal tract by normal tissue, is the least common dermatologic manifestation of Crohn's disease. We report a case of a 34-year-old man with metastatic Crohn's disease presenting as prepuce and scrotal edema with typical histopathologic features. We think that any unusual cutaneous lesion in patients with Crohn's disease should be biopsied.

Pathologic changes related to CMF primary chemotherapy in breast cancer. Pathological evaluation of response predicts clinical outcome.

The pathologic changes associated to response to primary chemotherapy in a series of 303 operable breast cancers are evaluated and correlated to patients' follow-up (interval free of disease and survival). In our series, the incidence of microscopic changes related to chemotherapy is 43.9%. Tumor replacement by loose fibrosis is the most common pathologic event. In most cases, the intensity of fibrotic change is proportional to the degree of clinical-mammographic reduction of the tumor mass. However, some discrepancies exist in the sense of absence of microscopic changes in cases of well-documented mammographic reduction as well as in cases without clinical reduction but with large areas of chemotherapy-related fibrosis. The presence of pathologic response is significantly associated with better survival rate.