Category Archives: Chapters

Firstly, we need to frame the condition we are evaluating within one of the five major chapters of Pathology:

             1- CONGENITAL MALFORMATIONS

             2- CIRCULATORY DISORDERS

             3- DEGENERATIVE PROCESSES

             4- INFLAMMATORY

             5-  NEOPLASTICS

          If the case was classified within the neoplasms chapter, our objective is to establish the diagnosis so that we can institute treatment. It is essential to establish an accurate diagnosis.

          To be diagnosed, it is necessary to know and learn the universe of tumors already described.

          Are we, as medical students, not already aware of all musculoskeletal neoplasms?

          We usually convey, in our classes, that our brain can store information randomly. However, if when we assimilate knowledge we try to do it in an orderly way, it will be “stored” in “folders”, these in “drawers” ​​and we will have a “ file ” . This way we can retrieve the information more easily.

          We will therefore help you build this  file,  organizing the  “HD” .

          Firstly, we need to remember that the neoplasm originates from a cell that already exists in our body. This cell, when reproducing, undergoes changes in its genetic code, due to different factors (radiation, viruses, mutations, translocations, etc.) and this then becomes the “ mother cell ” of the neoplasm.

          As we already learned histology at the Faculty, we are knowledgeable about all possible neoplasms. We just need to add some concepts to safely name and classify all the tumors already described.

The term carcinoma          was reserved  for malignant neoplasms whose primitive cells originate from the ectodermal layer and  sarcoma  for those from the mesoderm. 

          If we take our thigh as an example and do an exercise, remembering all the cells that make it up, starting with the skin and going deeper into the subcutaneous tissue, muscles, etc., up to the bone marrow of the femur, we will have reviewed all the cells of the locomotor system. and therefore we will be able to name all musculoskeletal neoplasms.

          Let’s do this exercise. Starting with the skin, we remember  squamous cell carcinoma ,  basal cell carcinoma  and  melanoma . These neoplasms are most frequently treated by dermatologists and plastic surgeons and only rarely require the help of an orthopedist.

          Below the skin, all structures are derived from the mesoderm and therefore we will add the suffix  oma for benign  lesions   and  sarcoma  for  malignant ones .

          Therefore, below the skin we have the subcutaneous cellular tissue (fat) whose most representative cell is the lipocyte. If the lesion is made up of cells similar to the typical lipocyte, we will have a  lipoma , consisting of disordered cells, with atypical mitoses, a  liposarcoma . In this same subcutaneous tissue we have fibroblasts, fibrohistiocytes and consequently  fibroma ,  fibrosarcoma ,  fibrohistiocytoma  of low and high degree of malignancy.

          Another structure that makes up our thigh are the striated muscles, (voluntary muscles), thus giving rise to  rhabdomyosarcoma . Smooth muscles, found in the locomotor system, are located around the vessels and, although they are rare, we also find  leiomyosarcoma .

          Nervous tissue is represented here by the axons of peripheral nerves. These axons have a sheath, whose cells were described by Schwann, from which  Schwannoma can originate .

           In soft tissues, remembering, as derived from lymphatic tissue,  lymphangioma  and  lymphangiosarcoma ; vascular tissue,  hemangioma  and  angiosarcoma .

          The bone is covered by the periosteum, whose function is to form bone tissue, in addition to protecting, innervating and nourishing. Trauma can lead to the formation of a sub-periosteal hematoma which, if mature, homogeneous ossification occurs, can be translated as a  periosteoma  (“osteoma”). Low-grade surface osteosarcoma  known as  paraosteal osteosarcoma  (grade I) as well as high-grade osteosarcoma can be derived from this same bone surface  .

          In our exercise we now reach the medullary region of the bone. This region is made up of fat, which can then lead to  intraosseous liposarcoma  and red bone marrow, from which we can have all neoplasms of the ERS ( Reticulum Endothelial System ) such as  plasma cell myeloma ,  lymphocytic lymphoma ,  Ewing’s sarcoma .

          If we remember, deep in our memory, the histology of endochondral ossification, we will find several precursor cells. One of them is large  (giant)  made up of cells with several nuclei, responsible for bone resorption, the osteoclast and consequently we have  osteoclastoma , better known as  giant cell tumor  ( GCT ). From the chondroblast the  chondroblastoma ; osteoblast  , osteoblastoma ; from the chondrocyte the  chondroma , the  chondrosarcoma ; and so on, we will be able to deduce all the neoplasms described. It will be enough to name them based on the knowledge of the normal cell, adding  oma  to the benign lesion and  sarcoma  to the malignant one.

          We consider this form of introduction to be important, as this way we will be better helped to remember what we already know and arrive at the diagnosis.

          The World Health Organization groups these injuries according to the tissue they try to reproduce, classifying them into:

I –  Tumors that form bone tissue

       Benign:  Osteoma – Osteoid Osteoma – Osteoblastoma

       Intermediate :  Aggressive Osteoblastoma

       Malignant :  Central Osteosarcoma – Parosteal – Periosteal – High Grade

II –  Cartilage-forming tumors

       Benign :  Chondroma (enchondroma) – Osteochondroma – Chondroblastoma – Chondromyxoid Fibroma

       Malignant :  Primary – Secondary – Juxtacortical – Mesenchymal – Dedifferentiated – Clear Cell Chondrosarcoma

III –  Giant Cell Tumors   (GCT) (Osteoclastoma)

IV –  Bone Marrow Tumors

         Malignant :  Ewing Sarcoma – Lymphocytic Lymphoma – Plasmocyte Myeloma – PNET

V –  Vascular Tumors

        Benign :  Hemangioma – Lymphangioma – Glomus tumor

        Intermediate :  Hemangioendothelioma – Hemangiopericytoma

       Malignant :  Angiosarcoma

VI –  Connective Tissue Tumors

         Benign :  Fibroma – Lipoma – Fibrohistiocytoma

         Malignant :  Fibrosarcoma – Liposarcoma – Malignant fibrohistiocytoma – Leiomyosarcoma – Undifferentiated sarcoma

VII –  Other tumors

           Benign :  Schwannoma – Neurofibroma

           Malignant :  Chordoma – Adamantinoma of the long bones

VIII –  Metastatic Tumors in the Bone

            Carcinomas: breast, prostate, lung, thyroid, kidney, neuroblastoma, melanoma, etc.

IX –  Pseudotumor Lesions

         Simple bone cyst (COS)

         Aneurysmal bone cyst (AOC)

         Juxta-articular bone cyst (intraosseous ganglion)

         Metaphyseal fibrous defect (Non-ossifying fibroma)

         Fibrous dysplasia

         Eosinophilic granuloma

        “Myositis ossificans”

        Brown tumor of hyperparathyroidism

        Intraosseous epidermoid cyst

        Giant cell reparative granuloma

         All of these lesions mentioned have  clinical particularities ,  imaging characteristics , and  histological aspects  that need to be analyzed together to correlate each one of them.

         This is fundamental, as we can have radiologically and/or histologically similar lesions but with different diagnoses.

         Therefore, imaging studies and histology must always be correlated with the clinical picture, for the correct diagnosis.

2. Parâmetros:

Devemos analisar os seguintes aspectos da lesão:

1) Identificar o osso ou ossos comprometidos;

2) Quanto ao número de lesões:  

          2.1) Localizada em um osso: monotópica;

          2.2) Uma lesão em diversos ossos: monotópica e poliostótica;

          2.3) Múltiplas lesões em um osso: politópica e monostótica;

          2.4) Múltiplas lesões em diversos ossos: politópica e poliostótica.

3) Quanto à localização no osso:

          3.1) Epífise, metáfise ou diáfisa;

          3.2) Região cortical, esponjosa, subperiostal, paraosteal ou justa-cortical;

          3.3) Central ou excêntrica.

4) Limites da lesão no osso:

          4.1) Precisos, imprecisos, infiltrativo ou permeativo, circundado ou não por esclerose reacional;

          4.2) Ultrapassa a cortical com lesão extra-óssea;

          4.3) Atinge as partes moles (sim/não) (desloca/infiltra);

          4,4) Ultrapassa a linha de crescimento.

5) Quanto ais aspectos da lesão:

          5.1) Destrutiva (osteolítica)

          5.2) Condensante ou osteogênica

          5.3) Multiloculada, “em bolhas de sabão”

          5.4) Calcificações: focais, difusas, estriadas

6) Tipo de reação periostal:

          6.1) Em lâminas finas – “em casca de cebola”

          6.2) Em lâminas grossas

          6.3) Espiculadas – “em raios de sol” ou “em pente”

          6.4) Levantamento periostal interrompido pelo tumor – Triângulo de Codman

3. Diagnóstico:

 Métodos de estudo para exame anátomo patológico:

 Citologia:

É o estudo de células descamadas obtidas em secreções, excreções ou obtidas com agulhas e realizando-se “imprints” (impressão de fragmentos de tecidos em lâminas). Raramente devera ser utilizado para diagnóstico de uma neoplasia óssea. Sua importância reside principalmente, na correlação cito-histológica.

Punção-biópsia:

Coleta de material com trefinas para inclusão em parafina e exame microscópico. Embora o material obtido por este método seja pequeno, quando é colhido em área significativa da neoplasia e por ortopedista com experiências no manuseio destas lesões, possibilita o diagnóstico definitivo. O local de obtenção deste material deve ser planejado pelo cirurgião, a fim de impedir ruptura do equilíbrio do tumor nos tecidos vizinhos, evitando sua disseminação.

Biópsia incisional:

É o método mais utilizado para diagnóstico de tumores ósseos. O local da biópsia deve ser planejado, não só quanto à área que possibilitará melhor diagnóstico histológico como para prever a futura ressecção do tumor, na qual deverá ser incluída a pele da região biopsiada. A biópsia não deverá ser realizada em locais inadequados do tumor como áreas de necrose,  hemorragia, no triângulo de Codman ou em áreas que apresentam apenas esclerose óssea reacional peritumoral.

Biópsia de congelação

É realizada durante o ato cirúrgico.  Este método não é indicado quando existir tecido ósseo. A possibilidade de erro diagnóstico é grande, nesta situação. Os erros de diagnóstico nas numerosas lesões ósseas com células gigantes multinucleadas, nos diversos tumores de células indiferenciadas, de células pequenas e redondas, a impossibilidade de diagnóstico diferencial histológico quando há tecido ósseo neoformado no calo de fratura, osteossarcoma e miosite ossificante, são alguns exemplos que contra-indicam o método. O exame em congelação poderá ser útil em casos de lesões metastáticas e mesmo assim, a rapidez do método não alterará a conduta operatória.

Estudo microscópico:

Os fragmentos obtidos por punção ou biópsia incisional devem ser incluídos em parafina e posteriormente faz-se a coloração com hematoxilina-eosina. Métodos especiais como PAS (Acido periódico de Schiff) e impregnação pela prata para estudo da reticulina são usualmente utilizados para diagnóstico diferencial, por exemplo, entre Sarcoma de Ewing, Linfomas e PNET (Tumor neuroectodérmico primitivo). O PAS, demostrando glicogênio e a escassa quantidade de reticulina, são usuais para diagnóstico de  sarcoma de Ewing. Nos Linfomas a reticulina é abundante e o PAS é negativo. Técnicas de imuno-histoquímica com imunoperoxidase estão entrando na rotina dos exames anatomopatológicos. São principalmente indicadas na procura do diagnóstico do órgão de origem de neoplasias metastáticas nos ossos. O uso de marcadores que permitem identificar a origem da célula neoplásica é cada vez mais usado na prática diária. Exemplos são o PSA, para identificar neoplasia originária da próstata, CK7 para neoplasia primitiva do pulmão, CK20 para neoplasia primitiva do tudo digestivo e receptores de estrógeno e progesterona para neoplasia da mama.

Peças cirúrgicas:

Rotineiramente uma peça cirúrgica deve ser examinada externamente e aos cortes. Externamente para análise das margens cirúrgicas com a finalidade de se verificar se a neoplasia foi completamente extirpada. Aos cortes verificamos o comprometimento do osso, extensão e  dimensões da neoplasia e seus caracteres macroscópicos principais para adequado estudo microscópico. (Figura 1) 

Quando o estudo de uma ressecção cirúrgica for de paciente submetido a quimioterapia pré-operatória, particularmente no osteossarcoma e no sarcoma de Ewing,  o estudo da  peça deverá obedecer uma sistematização de exame, pois a finalidade é analisar a resposta da neoplasia à terapêutica. As etapas do estudo serão as seguintes:

A) Serão feitas fatias da peça cirúrgica em toda sua extensão com espessura máxima de 0,5 cm,

B) Uma ou mais fatias deverão ser reproduzidas em “scanner” de computador ou fotografadas e radiografadas,

C) Esta reprodução deverá ser quadriculada da extremidade proximal até a distal,

D) Os fragmentos de cada área quadriculada deverão ser minuciosamente examinados ao microscópico com a finalidade de quantificar a necrose da neoplasia e a persistência de células tumorais histológicamente viáveis,

E) O relatório final do estudo de toda a peça deverá ser graduado quanto à resposta de quimioterapia pré-operatória nos critérios de Huvos.

Critérios de Huvos:

Grau I: Até 50% de necrose tumoral;

Grau II: de 50 a 90/% de necrose tumoral;

Grau III: Acima de 90% de necrose;

Grau IV: 100% de necrose tumoral – Ausência de células neoplásicas histológicamente viáveis.

Com esta graduação o oncologista poderá orientar o tratamento pós-operatório tendo em vista o pior prognóstico estatístico nos casos de gruas I e II e melhor nos de III e IV.

2. Parameters:

We must analyze the following aspects of the injury:

1) Identify the compromised bone or bones;

2) Regarding the number of injuries:  

          2.1) Located in a bone: monotopic;

          2.2) A lesion in several bones: monotopic and polyostotic;

          2.3) Multiple lesions in one bone: polytopic and monostotic;

          2.4) Multiple lesions in different bones: polytopic and polyostotic.

3) Regarding location in the bone:

          3.1) Epiphysis, metaphysis or diaphysis;

          3.2) Cortical, spongy, subperiosteal, paraosteal or juxta-cortical region;

          3.3) Central or eccentric.

4) Limits of bone injury:

          4.1) Precise, imprecise, infiltrative or permeative, surrounded or not by reactional sclerosis;

          4.2) It goes beyond the cortex with an extra-osseous lesion;

          4.3) It reaches the soft tissues (yes/no) (displaces/infiltrates);

          4.4) Exceeds the growth line.

5) Regarding other aspects of the injury:

          5.1) Destructive (osteolytic)

          5.2) Condensing or osteogenic

          5.3) Multiloculated, “in soap bubbles”

          5.4) Calcifications: focal, diffuse, striated

6) Type of periosteal reaction:

          6.1) In thin slices – “in onion skins”

          6.2) In thick sheets

          6.3) Spiculates – “in sunbeams” or “in a comb”

          6.4) Periosteal survey interrupted by the tumor – Codman’s Triangle

3. Diagnosis:

 Study methods for pathological anatomical examination:

 Cytology:

It is the study of desquamated cells obtained from secretions, excretions or obtained with needles and making “imprints” (printing tissue fragments on slides). It should rarely be used to diagnose bone neoplasia. Its importance lies mainly in the cytohistological correlation.

Punch-biopsy:

Collection of material with trephines for inclusion in paraffin and microscopic examination. Although the material obtained by this method is small, when it is collected from a significant area of ​​the neoplasia and by an orthopedist with experience in handling these lesions, it makes a definitive diagnosis possible. The location for obtaining this material must be planned by the surgeon, in order to prevent disruption of the tumor’s balance in neighboring tissues, preventing its spread.

Incisional biopsy:

It is the most used method for diagnosing bone tumors. The biopsy site must be planned, not only in terms of the area that will enable a better histological diagnosis but also to predict future resection of the tumor, which should include the skin of the biopsied region. The biopsy should not be performed in inappropriate locations of the tumor, such as areas of necrosis, hemorrhage, Codman’s triangle or in areas that only present peritumoral reactional bone sclerosis.

Frozen biopsy

It is performed during the surgical procedure. This method is not recommended when there is bone tissue. The possibility of a diagnostic error is high in this situation. Diagnostic errors in numerous bone lesions with multinucleated giant cells, in the various tumors of undifferentiated cells, small cells and round cells, the impossibility of a histological differential diagnosis when there is neoformed bone tissue in the fracture callus, osteosarcoma and myositis ossificans, are some examples that contraindicate the method. Frozen examination may be useful in cases of metastatic lesions and even so, the speed of the method will not alter the operative approach.

Microscopic study:

Fragments obtained by puncture or incisional biopsy must be embedded in paraffin and subsequently stained with hematoxylin-eosin. Special methods such as PAS (Periodic Acid Schiff) and silver impregnation to study reticulin are usually used for differential diagnosis, for example, between Ewing Sarcoma, Lymphomas and PNET (Primitive Neuroectodermal Tumor). PAS, demonstrating glycogen and a scarce amount of reticulin, are common for diagnosing Ewing’s sarcoma. In Lymphomas, reticulin is abundant and PAS is negative. Immunohistochemistry techniques with immunoperoxidase are entering the routine of anatomopathological examinations. They are mainly indicated in the search for the diagnosis of the organ of origin of metastatic neoplasms in the bones. The use of markers that allow identifying the origin of the neoplastic cell is increasingly used in daily practice. Examples are PSA, to identify neoplasia originating from the prostate, CK7 for primitive lung neoplasia, CK20 for primitive digestive tract neoplasia and estrogen and progesterone receptors for breast neoplasia.

Surgical parts:

Routinely a surgical specimen must be examined externally and at the cuts. Externally for analysis of surgical margins in order to verify whether the neoplasm was completely extirpated. In the sections, we verified the involvement of the bone, extension and dimensions of the neoplasm and its main macroscopic characters for adequate microscopic study. (Figure 1) 

When the study of a surgical resection is of a patient undergoing preoperative chemotherapy, particularly in osteosarcoma and Ewing’s sarcoma, the study of the specimen must follow a systematized examination, as the purpose is to analyze the response of the neoplasm to therapy. The study stages will be as follows:

A) Slices will be made of the surgical piece along its entire length with a maximum thickness of 0.5 cm,

B) One or more slices must be reproduced on a computer “scanner” or photographed and x-rayed,

C) This reproduction must be gridded from the proximal to the distal end,

D) The fragments from each checkered area must be thoroughly examined under a microscope in order to quantify the necrosis of the neoplasm and the persistence of histologically viable tumor cells,

E) The final report of the study of the entire specimen must be graded according to the response to preoperative chemotherapy according to the Huvos criteria.

Huvos Criteria:

Grade I: Up to 50% tumor necrosis;

Grade II: 50 to 90% tumor necrosis;

Grade III: Above 90% necrosis;

Grade IV: 100% tumor necrosis – Absence of histologically viable neoplastic cells.

With this degree, the oncologist will be able to guide post-operative treatment taking into account the worst statistical prognosis in cases of cranes I and II and better in those of III and IV.