Luis Samayoa

Ultrasound-Guided Fine-Needle Aspiration of Clinically Negative Lymph Nodes Versus Sentinel Node Mapping in Patients at High Risk for Axillary Metastasis

BackgroundSonographically directed fine-needle aspiration is a less invasive and less costly alternative to sentinel node (SN) mapping in breast cancer patients at high risk for metastatic disease but with clinically negative axillae.MethodsRadiographic, cytological, and histological diagnostic data on breast primary tumors from 114 consecutive SN candidates were prospectively assessed for clinicopathologic variables associated with an increased incidence of axillary metastases. Patients in whom these variables were identified underwent sonographic examination of their axillae followed by fine-needle aspiration when abnormal nodes were detected. SN mapping was performed in patients with normal axillary sonogram results or negative cytological results. Patients with positive cytological results proceeded to complete axillary dissection. Final axillary histological outcomes from patients not meeting the high-risk criteria were recorded. Additionally, a cost analysis was performed in which the costs of ultrasonography and ultrasound-guided fine-needle aspiration of the axilla were compared with those of SN mapping.ResultsAccording to our selection criteria, a third of the patients with clinically negative axillae (37 of 114; 32%) were considered at high risk for axillary metastases. Fifty-nine percent of these patients (22 of 37) had metastatic disease on final histological analysis. Forty percent (15 of 37) of high-risk patients were spared SN mapping, with a reduction in health care costs of 20% in this patient population. Eighty-seven percent of patients not meeting high-risk criteria were SN negative.ConclusionsThis study suggests that in patients at increased risk for axillary metastases, the use of sonographic evaluation of the axilla in combination with fine-needle aspiration is not only clinically justified, but also cost-effective.

Distinct lymph nodal sonographic characteristics in breast cancer patients at high risk for axillary metastases correlate with the final axillary stage

The purpose of this study was to assess the clinical relevance, limitations and most common findings of axillary ultrasound and subsequent image-guided aspiration cytology in clinically node-negative breast cancer patients who are at high risk for axillary metastasis. Following institutional review board approval and Health Insurance Portability and Accountability Act (HIPAA) compliance, sonographic axillary surveys from 112 patients considered at high risk for axillary metastases were reviewed retrospectively for the following abnormal features: asymmetric cortical thickening/lobulations; loss or compression of the hyperechoic medullary region; absence of fatty hilum; abnormal lymph node shape; hypoechoic cortex; admixture of normal and abnormal appearing nodes; and increased peripheral blood flow. Patients with either normal or abnormal ultrasound exams, but negative cytology, underwent sentinel node mapping. Patients with abnormal ultrasound and positive cytology proceeded to complete axillary dissection. The number of positive nodes, the size of tumour deposits and the histological pattern of metastatic disease on the positive nodes were then correlated and compared with their corresponding sonographic abnormalities. Abnormalities related to the lymph node cortex were indicative of N1a disease. Features such as loss or compression of the hyperechoic medullary region, absence of fatty hilum, abnormal lymph node shape and increased peripheral blood flow were predictors of N2-3 disease. In conclusion, nodal sonographic characteristics of patients at high risk for metastases are useful predictors of tumour burden in the axilla. When combined with the results from aspiration cytology, these findings could modify the surgical approach to the axilla, eliminating the need for sentinel node mapping in a significant proportion of patients.

Sentinel node micrometastasis in breast carcinoma may not be an indication for complete axillary dissection.

The decision whether to proceed with complete axillary node dissection based on sentinel node status is clear for patients with negative or macrometastatic disease. However, the course of action based on sentinel node micrometastasis remains controversial. We reviewed 358 cases from 6/1999 to 7/2003. All sentinel nodes were evaluated at three levels by frozen section, touch preparation, and scrape preparation. Micrometastasis was defined as tumor deposits between 0.2 and 2 mm. Size, grade, and lymphvascular invasion of the primary tumor, as well as number, status, size of metastatic disease, and presence of extranodal capsular extension of sentinel and nonsentinel nodes were recorded. Of the 358 cases, 89 had positive sentinel nodes, 29 of which represented micrometastases. Only one (3%) of the 29 cases contained a nonsentinel node with macrometastasis. In 60 of the 89 cases sentinel nodes contained macrometastases. Of these, 38 cases (63%) had metastatic tumor in nonsentinel nodes. Intraoperative consult was performed in 53 of the 89 cases with positive sentinel nodes. Only 1 of the 19 (5%) intraoperative consult cases with micrometastatic sentinel nodes had positive nonsentinel nodes, while 21 of 34 (62%) of macrometastatic sentinel nodes at intraoperative consult had tumor in nonsentinel nodes. No single variable studied discriminated between micro- vs macrometastatic disease. At intraoperative consult, macrometastatic disease was present in all three diagnostic preparations, while diagnostic material in micrometastatic sentinel nodes was usually present in only one modality. This analysis suggests that the risk of finding tumor in nonsentinel nodes differs significantly between cases with micro (3%)- vs macro (63%)-metastatic disease in sentinel nodes. This holds true for cases assessed by intraoperative consult. Considering the known morbidity of complete axillary dissection, assessments of risk vs benefit of undertaking this procedure should be performed on a case-by-case basis in patients with sentinel node micrometastases.

The Critical Role of Axillary Ultrasound and Aspiration Biopsy in the Management of Breast Cancer Patients with Clinically Negative Axilla

BackgroundSonographic evaluation of the axilla can predict node status in a significant proportion of clinically node-negative patients. This review focuses on the value of ultrasound followed by ultrasound-guided cytology in assessing the need for sentinel node mapping and conservative versus complete axillary dissections.DesignBreast primaries from 168 sentinel node candidates were prospectively assessed for clinicopathologic variables associated with increased incidence of axillary metastases. Patients were classified accordingly, and those at a higher risk underwent ultrasound of their axillae, followed by aspiration biopsy if needed. Sentinel node mapping was performed in all low-risk patients, and in high-risk patients with normal axillary ultrasounds or negative cytology. Final axillary status was compared in terms of nodal stage, number of positive nodes, and size of metastasis.Results112 patients were at high risk for nodal disease (67%), with a statistically significant lower probability for remaining node-negative and a statistical significantly higher risk for having more than one positive node. All patients with more than three positive nodes were detected by ultrasound-guided cytology. High-risk patients with final positive axillae missed by ultrasound or ultrasound guided cytology had tumor deposits measuring ≤5 mm.ConclusionExtent of axillary dissections can be decided based on the risk for axillary metastases: sentinel node mapping for low-risk patients; less-aggressive axillary dissections for high-risk patients with negative ultrasound and/or negative cytology; and a standard dissection for high-risk patients with positive cytology.

Secondary Angiosarcoma of the Breast: Can Imaging Findings Aid in the Diagnosis?

Abstract:  Secondary angiosarcomas, although rare, are aggressive tumors that can develop in breast tissue that has undergone prior radiation therapy. We present three cases of secondary angiosarcoma of the breast in the setting of prior breast irradiation. Imaging findings include cutaneous nodules and progressive skin or trabecular thickening in an area of the breast separate from the patient’s original breast carcinoma. These imaging findings may enable the radiologist to suggest this diagnosis, even when the clinical presentation is more benign.

Should Histologic Grade Be Incorporated into the TNM Classification System for Small (T1, T2) Node-Negative Breast Adenocarcinomas?

Prognosis of invasive ductal carcinoma (IDC) strongly correlates with tumor grade as determined by Nottingham combined histologic grade. While reporting grade as low grade/favorable (G1), intermediate grade/moderately favorable (G2), and high grade/unfavorable (G3) is recommended by American Joint Committee on Cancer (AJCC) staging system, existing TNM (Primary Tumor/Regional Lymph Nodes/Distant Metastasis) classification does not directly incorporate these data. For large tumors (T3, T4), significance of histologic grade may be clinically moot as those are nearly always candidates for adjuvant therapy. However, for small (T1, T2) node-negative (N0) tumors, grade may be clinically relevant in influencing treatment decisions, but data on outcomes are sparse and controversial. This retrospective study analyzes clinical outcome in patients with small N0 IDC on the basis of tumor grade. Our results suggest that the grade does not impact clinical outcome in T1N0 tumors. In T2N0 tumors, however, it might be prognostically significant and relevant in influencing decisions regarding the need for additional adjuvant therapy and optimal management.

Myeloid sarcoma of the breast misdiagnosed as poorly differentiated mammary carcinoma with lobular features.

A 46-year-old Caucasian female was referred to the breast center with complaints of an enlarging, tender breast mass. She had noticed the mass 5 days prior to presentation, and reported that it was accompanied by mild swelling and a burning sensation. On physical exam, she was noted to have a palpable abnormality in the right breast, although examination was somewhat limited by dense breast tissue bilaterally. A mammogram performed 18 months earlier was normal (Fig. 1). The patient’s clinical history was

Primary pulmonary synovial sarcoma presenting as a breast mass.

A52-year-old woman with no pertinent personal or family history of cancer was found on screening mammography to have an abnormality in the right breast. The mammogram showed a 9-mm oval mass with indistinct borders that appeared to be solid on ultrasonographic examination (Fig. 1). Ultrasoundguided core needle biopsy of the breast lesion retrieved multiple tissue fragments of the right breast nodule for histologic examination. Microscopically, the tissue fragments demonstrated a circumscribed, nonencapsulated tumor composed of fasciculi and bundles of pleomorphic spindle cells with large oval nuclei. Numerous mitotic figures were present (5 mitoses per 10 high-power fields). The adjacent breast parenchyma showed normal lobular units (Fig. 2). Immunohistochemical and molecular genetic studies confirmed the diagnosis of synovial sarcoma. Since primary synovial sarcoma of the breast had not been described previously, the breast mass was highly suspicious for metastatic disease. Five weeks later, computed tomography was performed of the chest, abdomen, pelvis, and upper and lower extremities. There was no evidence of tumor in the extremities. However, a nodule (3.1 · 2.5 cm) was found in the upper lobe of the right lung (Fig. 3). Computed tomography—guided fine-needle aspiration

Collagen prolyl 4-hydroxylase 1 is essential for HIF-1α stabilization and TNBC chemoresistance

Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. Here, we show that P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer. By modulating alpha ketoglutarate (α-KG) and succinate levels P4HA1 expression reduces proline hydroxylation on hypoxia-inducible factor (HIF) 1α, enhancing its stability in cancer cells. Activation of the P4HA/HIF-1 axis enhances cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species (ROS) levels. Inhibition of P4HA1 sensitizes TNBC to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived models. We also show that increased P4HA1 expression correlates with short relapse-free survival in TNBC patients who received chemotherapy. These results suggest that P4HA1 promotes chemoresistance by modulating HIF-1-dependent cancer cell stemness. Targeting collagen P4H is a promising strategy to inhibit tumor progression and sensitize TNBC to chemotherapeutic agents.Hyperactivation of HIF-1α is crucial in progression of triple-negative breast cancer, but how HIF-1α stability is maintained in a hypoxia-independent manner is unclear. Here, the authors show collagen prolyl-4-hydroylase 1 stabilises HIF-1α and is involved in chemoresistance in TNBC.

PROGRESSIVE LANGERHANS’ CELL HISTIOCYTOSIS PRESENTING AS A PRIMARY PENILE LESION

A 3-year-old white male was referred with a 6-month history of a solitary penile lesion unresponsive to topical and oral antibiotics. Physical examination revealed a solitary 1 1 cm. shallow, nontender ulcer on the dorsal prepuce. A circumcision with excision of the lesion was performed without complication. On routine followup the incision was healed and no new lesions were noted. Histopathological studies showed an atypical inflammatory type of infiltrate composed of histiocytes with characteristic convoluted, cerebriform nuclei demonstrating strong S-100 immunohistochemical positivity consistent with Langherhans’ cell histiocytosis. Elec-