Faculty Bibliography

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is rare but is one of the most aggressive and lethal human malignancies. Cytologically, ATC has a variable morphologic appearance, including squamoid, giant, spindled and pleomorphic cells. The coexistence of ATC and differentiated or poorly differentiated thyroid carcinoma has been described and usually is diagnosed when the disease is locally advanced. CASE: We describe a case of surgically resectable, encapsulated, well-circumscribed ATC occurring in association with a better differentiated follicular carcinoma diagnosed by fine needle aspiration in a patient exposed to external ionizing radiation. CONCLUSION: Encapsulated variants of anaplastic carcinoma can be seen in association with lower grade thyroid carcinoma such as follicular carcinoma. Accurate diagnosis is dependent on adequate sampling

Ductal carcinoma in situ with microinvasion (DCISM) is a distinct clinicopathologic entity. Its true metastatic potential has been unclear, due in part to historical differences in the definition of microinvasion. The role of routine axillary staging for DCISM is controversial, given the reportedly low incidence of axillary metastases. We describe our institutional experience with DCISM, and define the role of axillary staging. A retrospective analysis was made of patients with DCISM. Forty-four patients underwent axillary staging (24 axillary lymph node dissection [ALND], 22 sentinel node biopsy [SNB]). Macrometastatic disease was present in three patients (7%), and two patients had isolated tumor cells (itc) in the sentinel node. Patients with axillary metastases tended to be younger. Comedonecrosis, nuclear grade, multifocal microinvasion or presentation as a clinical mass was not associated with a higher rate of axillary metastases. In this series, 7% of patients had macrometastatic disease, and two patients (5%) had itc only. Axillary staging is indicated, and SNB is appropriate for the identification of axillary metastatic disease

CONTEXT: Both atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) have traditionally been considered to be risk factors for the development of invasive carcinoma and are followed by close observation. Recent studies have suggested that these lesions may represent true precursors with progression to invasive carcinoma. Due to the debate over the significance of these lesions and the small number of cases reported in the literature, the treatment for lobular neoplasia diagnosed by percutaneous core biopsy (PCB) remains controversial. OBJECTIVE: To review our experience with pure LCIS or ALH diagnosed by PCB and correlate the radiologic findings and surgical excision diagnoses to develop management guidelines for lobular neoplasia diagnosed by PCB. DESIGN: We searched the pathology database for patients who underwent PCB with a diagnosis of either pure LCIS or ALH and had subsequent surgical excision. We compared the core diagnoses with the surgical excision diagnoses and the radiologic findings. RESULTS: Thirty-eight PCBs with a diagnosis of ALH (18 cases) or LCIS (20 cases) were identified. Carcinoma was present at excision in 1 (6%) of the ALH cases and in 2 (10%) of the LCIS cases. In summary, 8% (3/38) of PCBs diagnosed as lobular neoplasia (ALH or LCIS) were upgraded to carcinoma (invasive carcinoma or ductal carcinoma in situ) at excision. CONCLUSIONS: Surgical excision is indicated for all PCBs diagnosed as ALH or LCIS, as a significant percentage will show carcinoma at excision

Sentinel node biopsy has become the standard method for lymphatic staging in early-stage breast cancer and melanomas. The most commonly used technique uses both a radioactive tracer as well as blue dye, usually isosulfan blue. In this report, we discuss two episodes of anaphylaxis to isosulfan blue during lymphatic mapping, occurring 12 years and 3339 lymphatic mapping cases after adoption of the technique, and discuss management issues raised by these events

Membrane-type 1 matrix metalloproteinase (MT1-MMP), a transmembrane proteinase with a short cytoplasmic domain and an extracellular catalytic domain, controls a variety of physiological and pathological processes through the proteolytic degradation of extracellular or transmembrane proteins. MT1-MMP forms a complex on the cell membrane with its physiological protein inhibitor, tissue inhibitor of metalloproteinases-2 (TIMP-2). Here we show that, in addition to extracellular proteolysis, MT1-MMP and TIMP-2 control cell proliferation and migration through a non-proteolytic mechanism. TIMP-2 binding to MT1-MMP induces activation of ERK1/2 by a mechanism that does not require the proteolytic activity and is mediated by the cytoplasmic tail of MT1-MMP. MT1-MMP-mediated activation of ERK1/2 up-regulates cell migration and proliferation in vitro independently of extracellular matrix proteolysis. Proteolytically inactive MT1-MMP promotes tumor growth in vivo, whereas proteolytically active MT1-MMP devoid of cytoplasmic tail does not have this effect. These findings illustrate a novel role for MT1-MMP-TIMP-2 interaction, which controls cell functions by a mechanism independent of extracellular matrix degradation