Abstract:
A carrier and method of using to orient and maintain an excised tissue sample in an orientation sufficient to determine its position in a body. The carrier permits radiological and pathological evaluation of a precisely and accurately oriented tissue specimen. The carrier is comprised of an outer box open at a lateral end for receiving a specimen, and a slidably insertable inner box for containing and minimally compressing the specimen. The specimen is marked and maintained in its in vivo orientation from the time of excision and is evaluated for localization and orientation of a tumor during radiological and/or pathological assessment. The carrier and method increase the accuracy and efficiency of diagnosis and any subsequent treatment.

Description:
FIELD OF THE INVENTION 
     The invention relates to a carrier to maintain an excised tissue specimen such as a breast biopsy specimen in a defined and stable orientation throughout subsequent processing and evaluation. 
     BACKGROUND 
     Mammography is a noninvasive screening method for early detection of breast cancer. By pinpointing lesions as small as a few millimeters for further evaluation, mammography is an effective way to detect early-stage breast cancer, leading to increased treatment efficacy and decreased morbidity and mortality. The prevalence of mammography has led to increased follow-up evaluation including surgical biopsies of suspicious lesions or masses. 
     Among the diagnostic evaluation protocols, gross and microscopic pathological examination of excised suspicious tissues is routinely performed. This often consists of macroscopically examining the intact tissue, then histologically processing the tissue for subsequent microscopic evaluation of one or more stained serial sections. In addition, radiologic evaluation of the tissue, either in an intact form or in serial sections, may be performed. 
     In evaluating an excised tissue sample for the presence of malignant, pre-malignant or suspicious cells, it is useful if the tissue is maintained in an undistorted manner and in the exact orientation from which it was removed from the body. Maintaining tissue orientation permits a clinician to determine the extent of any malignancy that may be present; for example, if the tissue margins are free from malignant cells, the clinician is given greater assurance that the entire lesion was excised. This lessens the need for subsequent or more invasive surgery or other procedure. In contrast, if the tissue margins contain malignant, pre-malignant or suspicious cells, further surgery may be desirable to ensure that more or all of a mass is removed. 
     A variety of devices are available for securing and transporting such excised tissues for pathologic and/or radiologic evaluation. For example, tissue samples can be sandwiched and compressed between two plates, with the plates forming a grid for locating a mass within a tissue sample during subsequent radiological and pathological evaluation. As another example, tissue samples may be contained in carriers that have multiple compartments to contain core tissue samples as well as peripheral tissue samples to ensure the core tumor as well as the surrounding tissue is evaluated. As still another example, tissue samples may be contained in molds that vertically orient specimens prior to histological embedding and processing. None of these devices, however, minimize distortion of the tissue and maintain tissue orientation during transport and radiological and/or pathological evaluation so that, for example, accurate assessment of tissue margins may be made. 
     SUMMARY OF THE INVENTION 
     The invention is directed to a tissue specimen carrier that minimizes specimen distortion and maintains in vivo orientation of the tissue from excision throughout transport and radiological and/or pathological evaluation. The carrier is a radiographically transparent outer device or box to contain the tissue in a known fixed orientation, with the outer box open at at least one face for receiving a slidably insertable radiographically transparent inner device or box, and the inner box for securing the specimen contained in the outer box. In one embodiment, the carrier has a plurality of apertures at least one surface. The carrier may be appropriately sized to contain a tissue specimen that is in the range of, for example, about one to about five times smaller than the size of the carrier. 
     The invention also relates to a method of maintaining an excised tissue specimen in a defined and stable orientation relative to its orientation in the body throughout radiologic and/or pathologic evaluation. The specimen may be a breast biopsy specimen. 
     The invention additionally relates to a method of providing an oriented orthogonal view of an excised tissue from a body for subsequent diagnostic evaluation. The specimen is oriented relative to its location in the body, and is inserted into a carrier and maintained in the fixed oriented position throughout diagnosis. 
    
    
     The invention is also directed to a method of providing accurate radiographic margin assessment of an excised breast tissue specimen comprising orienting the excised tissue relative to its position in the body, inserting the oriented tissue into a carrier comprising an outer box open at at least one face end and a slidably insertable inner box, exerting a force on the inner box sufficient to conform the tissue roughly to a dimension of said outer box, and performing said assessment on the contained oriented tissue. The excised breast tissue may be obtained from a biopsy, a lumpectomy, or a mastectomy. These and other advantages of the invention will be further understood with reference to the following figures and detailed description. 
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a perspective view of the tissue specimen apparatus containing an excised and oriented tissue specimen. 
     FIG. 2 is a perspective view of an oriented excised tissue specimen. 
     FIG. 3 is a perspective view of a tissue specimen prepared for sectioning. 
     FIG. 4 is a cross-sectional view of the apparatus taken along line  4 — 4  of FIG.  1 . 
    
    
     DETAILED DESCRIPTION 
     As shown in FIG. 1, a carries apparatus or device  10  to contain and maintain a surgically excised tissue specimen  12  in a defined orientation relative to its removal from a body is disclosed. The excised tissue specimen  12  may be a biopsy or other specimen known or suspected of containing a tumor, lesion, cyst or mass of cells that requires further diagnostic or therapeutic evaluation or examination, for example, to determine if malignant, pre-malignant, suspicious or otherwise abnormal cells are present. 
     The carrier  10  comprises an outer compartment or box  20  that is open at at least one face  22  for stably containing and maintaining the excised specimen  12  in a known and fixed orientation, and a slidably insertable inner compartment or box  24  to secure and conform the specimen  12  contained therein. While a rectangular shaped box is preferable for ease of subsequent histological processing, the carrier  10  is not limited to this shape and may be, for example, square, circular or any other geometric shape. The outer box  20  and inner box  24  are preferably completely separable, but they may also form a unitary device with the outer box  20  and inner box  24  connected by, for example, a hinge or other connector. In one embodiment, a series of different sized carriers  10  are available to accommodate various sized biopsy specimens  12 . A surgeon or practioner then selects the carrier  10  that is sized to either just accommodate a tissue specimen  12  or to contain a smaller-sized specimen  12 . Preferably, the carrier  10  is sized to encompass specimens  12  ranging from about 2×2 cm to about 10×8 cm, and may range from about one to about five times the specimen  12  size. 
     The outer box  20  and inner box  24  are made of a radiographically transparent material  26 . Examples of such radiographically transparent material  26  are extruded plastics, which may be either clear or colored. The edges or beams are preferably thin so the carrier  10  can be cut or otherwise easily opened during subsequent tissue processing. It is preferred that the material  26  is also visually transparent to allow gross inspection of the specimen  12  contained therein. 
     The material  26  may have an orientation marking system  39  stamped or otherwise applied thereon to allow the surgeon to select a marking  39  for a particular orientation. The marking system  39  may be a coordinate system such as an x, y, z coordinate system  39  with which medical personnel are familiar, or another system. The system  39  is preferably visible on radiographic films to allow the radiologist to maintain orientation of the specimen  12  while viewing the films. 
     As shown in FIG. 4, the interior surface  31  of the outer box  20  may have one or more projections or barbs  33 . The barbs  33  are preferably located in a region of the inner surface  31  that will contact the specimen  12  and may serve to secure the specimen  12  in the carrier  10 . The barbs  33  may be of any material but are preferably the same material  26  as the carrier  10  and can be configured to project inwardly from an aperture  30 . The barbs  33  are preferably about 1-5 mm long and may terminate in a substantially pointed tip so that they contact a portion of specimen  12  to assist in securing the specimen  12  in the carrier  10 . In this embodiment, a contact of about one to a few mm into the specimen  12  is sufficient as long as the barb  33  catches or hooks into a portion of the specimen  12 . In an alternative embodiment, the barbs do not hook into the specimen  12  but provide an external barrier to movement of the specimen  12  within the outer box  20 . 
     The apparatus  10  is configured so that the material  26  defines a plurality of apertures  30 , preferably having a square shape and preferably sized to accommodate a monofilament suture. The aperture  30  size is preferably in the range of about 1 mm to about 9 mm. The apertures  30  are preferably regularly spaced  32  to form grids of about 1 cm and are preferably present through each face  34  of the outer box  20  and through at least two opposing faces of the inner box  24 . 
     With reference to FIG. 2, in use, a tissue sample  12  is excised from the body and is placed in the outer box  20  in the exact orientation from which it was located in and removed from the body. The tissue sample frequently is suspected of containing or may in fact be known to contain a tumor, mass, lesion, or cluster of suspicious or abnormal cells  36 . The sample  12  may be, for example, breast tissue obtained by ultrasonographic or stereotactic guided core excision, excision preceded by insertion of a wire under mammographic guidance for localization of an impalpable abnormal shadow or microcalcification (needle localization biopsy), lumpectomy of a defined or palpable mass or from a partial or total mastectomy. The method and device, however, are not limited to use with breast tissue specimens and may be used with any excised solid tissue specimen, preferably requiring orientation with further evaluation such as a cyst or a solid organ specimen, for example, a liver biopsy specimen. 
     The invention permits a tissue specimen  12  to be accurately and fixedly maintained in the exact orientation as it was located and positioned in vivo. The excised specimen  12  is initially oriented by marking the specimen  12 , usually visually marking using any convenient means such as placing any type of device or combination of devices such as pins, clips, sutures, etc. on or into the specimen  12 . In one embodiment, the specimen  12  is oriented by placing sutures  40  of varying lengths at one or more defined positions in the specimen  12 . For example, a shorter suture  42  may be placed at the superior extreme  44  of the specimen  12 , and a longer suture  45  may be placed at a lateral extreme  46  of the specimen  12 . 
     The specimen  12  thus oriented is placed into the outer box  20  of the carrier  10 . It is particularly convenient to place the specimen  12  into the carrier  10  by grasping the specimen  12  by its anterior surface  48  and placing it into the carrier  10  by inserting the specimen  12  through at least one open face  22  so that its superior extreme  44  is oriented to the craniocaudacad (CC) face and the lateral extreme  48  is oriented to the mediolateral (ML) face. 
     A device  10  is selected from among a plurality of different-sized devices to either just accommodate the specimen  12  or to be in the range of preferably about one to five times larger than the specimen  12 . An appropriately sized device  10  permits fixed and stable transport of a specimen  12 . However, it will be appreciated that while a carrier  10  that is sized to be in the range of about one to about five times as large as the specimen  12  is preferred, any carrier  10  that is either the same size or larger than the specimen  12  may be used. 
     The interior compartment or box  24  is then inserted into the outer box  20  and is adjusted to stably contain the specimen  12  within the outer box  20 . This is most easily accomplished by exerting a minimal compressive force, preferably by hand, on a surface of the inner box  24  sufficient for the inner box  24  to touch the outer surfaces of the specimen  12 . A minimally compressive force is one that serves to substantially conform the specimen  12  to at least one surface of the inner box and to preferably form the specimen  12  in a substantially rectangular shape. This shape aids in subsequent tissue processing. The force further fixedly maintains the oriented tissue specimen  12  within the device  10 , and also textures or nubs  50  the specimen surface. Sufficient texturing or nubbing on the surface of the specimen  12  is achieved by the regularly spaced, preferably square shaped apertures  30  and facilitates free-hand serial sectioning of the specimen  12 . 
     After orientation of the specimen  12  is verified, the specimen  12  is secured within the inner box  24 . This may be accomplished as the specimen  12  contacts the barbs  33  that inwardly project on an interior surface  31  of the outer box  20 . This may additionally or alternatively be accomplished by inserting a suture  40  through an aperture  30  of the outer box  20  so that the suture  40  is inserted into the specimen  12 . The inner box  24  is further secured in the outer box  20 . In one embodiment, the inner box  24  is secured by an additional securing means, for example, by a straight suture  40  inserted through apertures  30   a,    30   b  (not shown) in both the inner box  24  and outer box  20 . 
     The specimen  12  that is oriented and fixed in an appropriately sized carrier  10  is then subjected to radiography. For example, the carrier  10  is placed against a photographic film and is exposed to x-rays. Radiographic films are obtained in both the CC and ML projections, corresponding to the orientation of any suspected lesion or mass  36  visualized on the film. Ideally, both the radiologist and surgeon view the film and may consult to determine whether to excise additional tissue. Additional tissue would likely be required if, for example, the film showed that the margins of the excised tissue  12  contained a suspicious or abnormal area or shadow. 
     The specimen  12 , still maintained in an oriented and fixed position in the appropriately sized carrier  10 , is then subjected to pathological evaluation. The carrier  10  may be transported for pathological evaluation by any timely means that will not compromise the specimen  12  orientation and integrity. The specimen  12  stably maintained in the carrier  10  is then subjected to histological processing. For example, the specimen  12  may be treated to cause tissue fixation and render the cellular structural components insoluble by immersing the carrier  10  containing the specimen  12  in a rapid fixation system solution such as a solution of 70-30 formyl alcohol (formalin 70% and isopropanol 30%) for at least four hours and up to about 18 hours. 
     With reference to FIG. 3, after fixation the specimen  12  having roughly a rectangular shape and a nubbed surface is removed while still maintaining orientation. Removal of the specimen  12  may be by any means that maintains orientation and integrity of the specimen  12 . For example, the specimen  12  may be removed by grasping a laterally placed suture  45 , either directly or using a device such as forceps or a hemostat, and applying gentle force to dislodge the specimen  12  from the carrier  10 . As another example, the specimen  12  may be removed by cutting through the carrier  10 , for example, at a thin edge, using any appropriate cutting tool such as a scalpel or scissors. 
     The specimen  12  is then immediately coded to differentiate each surface  44 ,  46 ,  48 . This may be done, for example, by painting each surface  44 ,  46 ,  48  of the specimen  12  with a different colored ink and fixing the ink with a chemical mordant. 
     The specimen  12  is then sectioned in accordance with standard pathologic technique, for example, in a sagittal plane for subsequent processing. The fixed tissue specimen  12  is embedded or infiltrated with a solution of paraffin or other solution that solidifies so that the tissue and the embedding matrix may be sectioned together. The fixed, ordered and oriented sections  60  may be further evaluated radiologically. This would be of use, for example, in the case where microcalcifications, an early indicator of tumor formation in breast tissue, were noted and required closer evaluation. Alternatively or additionally, the sections  60  may be placed in cassettes or other types of suitable packaging for further histological processing such as staining for pathological evaluation. 
     It should be understood that the embodiments of the present invention shown and described in the specification are only preferred embodiments of the inventor and are not limiting in any way. Therefore, various changes, modifications or alterations to these embodiments may be made or resorted to without departing from the spirit of the invention and the scope of the following claims.