Atypical Colitides

Two atypical colitides—collagenous colitis and lymphocytic colitis—have completely normal endoscopic appearances. 

Collagenous colitis has two main histologic components: increased subepithelial collagen deposition and colitis with increased intraepithelial lymphocytes. The female to male ratio is 9:1, and most patients present in the sixth or seventh decades of life. The main symptom is chronic watery diarrhea. Treatments range from sulfasalazine or mesalamine and Lomotil to bismuth to budesonide to prednisone for refractory disease.

Lymphocytic colitis has features similar to collagenous colitis, including age at onset and clinical presentation, but it has almost equal incidence in men and women and no subepithelial collagen deposition on pathologic section. However, intraepithelial lymphocytes are increased. The frequency of celiac disease is increased in lymphocytic colitis and ranges from 9 to 27%. Celiac disease should be excluded in all patients with lymphocytic colitis, particularly if diarrhea does not respond to conventional therapy. Treatment is similar to that of collagenous colitis with the exception of a gluten-free diet for those who have celiac disease.

Diversion colitis is an inflammatory process that arises in segments of the large intestine that are excluded from the fecal stream. It usually occurs in patients with ileostomy or colostomy when a mucus fistula or a Hartmann's pouch has been created. Clinically, patients have mucus or bloody discharge from the rectum. Erythema, granularity, friability, and, in more severe cases, ulceration can be seen on endoscopy. Histopathology shows areas of active inflammation with foci of cryptitis and crypt abscesses. Crypt architecture is normal, which differentiates it from UC. It may be impossible to distinguish from CD. Short-chain fatty acid enemas may help in diversion colitis, but the definitive therapy is surgical reanastomosis.

Differences - Ulcerative colitis & Crohn's Disease

ULCERATIVE                   CROHN'S                                                                                               COLITIS                          DISEASE Clinical
Gross blood in stool	Yes	Occasionally
Mucus	Yes	Occasionally
Systemic symptoms	Occasionally	Frequently
Pain	Occasionally	Frequently
Abdominal mass	Rarely	Yes
Significant perineal disease	No	Frequently
Fistulas	No	Yes
Small intestinal obstruction	No	Frequently
Colonic obstruction	Rarely	Frequently
Response to antibiotics	No	Yes
Recurrence after surgery	No	Yes
ANCA-positive	Frequently	Rarely
ASCA-positive	Rarely	Frequently
Endoscopic
Rectal sparing	Rarely	Frequently
Continuous disease	Yes	Occasionally
"Cobblestoning"	No	Yes
Granuloma on biopsy	No	Occasionally
Radiographic
Small bowel significantly abnormal	No	Yes
Abnormal terminal ileum	No	Yes
Segmental colitis	No	Yes
Asymmetric colitis	No	Yes
Stricture	Occasionally	Frequently

Primary Genetic Disorders Associated with Ibd

Name Genetic Association Phenotype Turner's syndrome Loss of part or all of X chromosome Associated with UC and colonic CD Hermansky-Pudlak Autosomal recessive chromosome 10q23 Granulomatous colitis, oculocutaneous albinism, platelet dysfunction, pulmonary fibrosis Wiskott-Aldrich syndrome (WAS) X-linked recessive disorder, loss of WAS protein function Colitis, immunodeficiency, severely dysfunctional platelets, and thrombocytopenia Glycogen Storage disease Deficiency of the glucose-6-phosphate transport protein type B1 Granulomatous colitis, presents in infancy with hypoglycemia, growth failure, hepatomegaly, and neutropenia Immune dysregulation polyendocrinopathy, enteropathy X-linked (IPEX) Loss of FoxP3 transcription factor and T regulatory cell function UC-like autoimmune enteropathy, with endocrinopathy (neonatal type 1 diabetes or thyroiditis), dermatitis Early onset IBD Deficient IL-10 receptor function Severe, refractory IBD in early life

Epidemiology of IBD

Ulcerative Colitis Crohn's Disease Incidence (North America) per person-years 2.2–14.3:100,000 3.1–14.6:100,000 Age of onset 15–30 & 60–80 15–30 & 60–80 Ethnicity Jewish > non-Jewish white > African American > Hispanic > Asian Male/female ratio 1:1 1.1–1.8:1 Smoking May prevent disease May cause disease Oral contraceptives No increased risk Odds ratio 1.4 Appendectomy Protective Not protective Monozygotic twins 6% concordance 58% concordance Dizygotic twins 0% concordance 4% concordance

Amyand's hernia

Amyand's hernia is a rare form of inguinal hernia (less than 1%) which occurs when the appendix is included in the hernial sac and becomes incarcerated. The condition is an eponymous disease named after an English surgeon, Claudius Amyand , who performed the first successfulappendectomy in 1735.

Amyand's hernia is commonly misdiagnosed as an ordinary incarcerated hernia. Symptoms mimicking appendicitis may occur. Treatment consists of a combination of appendectomy and hernia repair.

Arcade of frohse

The most superior part of the superficial layer of the supinator muscle is named as the arcade of Frohse (AF). The deep branch of the radial nerve runs under this arch. The AF is reported to be the most common structure causing entrapment neuropathy of the deep branch of the radial nerve(PIN syndrome).

Osborne's ligament ( Band of Osborne )

roof of cubital tunnel is formed by aponeurosic attachment of 2 heads of FCU, which spans in arcade like manner from medial 
                epicondyle of humerus to the olecranon process of the ulna (also known as Osborne's ligament);
                - cubital tunnel begins where the ulnar nerve passes beneath Osborne's ligament;

Arcade of Struthers

    - in middle of the arm, ulnar nerve pierces medial intermuscular septum and descends in front of the medial head of the triceps;

    - in 70-80% of individuals, nerve passes under arcade of Struthers;
    - the arcade is a thin aponeurotic band extending from medial head of triceps to the medial intermuscular septum;
           - it lies approximately 8 cm proximal to the medial epicondyle;
    - the arcade may appear as medial triceps muscle fibers crossing superficial to the ulnar nerve;
    - arcade is not site for entrapment under ordinary circumstances, but it may become point of kinking if anterior transposition of ulnar nerve is performed;
           - following transposition procedures, the surgeon should release the arcade if it appears that the nerve is under tension;

Important bone tumours

Bone infarct

"smoke up the chimney"

medullary lesion of sheet-like central lucency surrounded by sclerosis with a serpiginous border

Ewing's sarcoma

Introduction

A malignant small round cell tumor found in young patients Age & location found in patients from 5-25 years of age ~50% are found in the diaphysis of long bones common locations include the femoral shaft, knee (distal femur and prox tibia), pelvis and proximal humerus Genetics 90% have t(11:22) translocation which leads to the formation of a fusion protein (EWS-FLI 1) Prognosis 60-70% long term survival with treatment only 40% long term survival with pelvis lesions only 15% long term survival if patient presents with metastasis to the lung

Symptoms

Presentation pain often accompanied by fever often mimics an infection Physical exam swelling and local tenderness

Imaging

Radiographs large destructive lesion in the diaphysis or metaphysis with a moth-eaten appearance  periosteal lifting may give "onion skin" or "sunburst" appearance Bone scan hot required as part of workup MRI often shows a large soft tissue component  CT chest is important to rule out mets to lungs (very common)

Labs

ESR is elevated WBC is elevated Anemia is common Bone marrow biopsy  required as part of workup for Ewing's to rule out metastasis to the marrow

Histology

Characteristic findings sheets of monotonous small cells  cells have scant cytoplasm  may have pseudo-rosettes (circle of cells with necrosis in center)  Immunostain CD99 reactivity

Treatment

Multimodality multistage chemotherapy and limb salvage resection preoperative chemotherapy given for 8-12 weeks followed by maintenance chemotherapy for 6-12 months after surgical resection  irradiation current trend towards surgical resection and away from irradiation due to high risk of irradiation-induced secondary malignancies situations where radiation can be used include  radiation alone for areas that cannot be resected (ie, large bulky pelvic tumors), in combination with local resection if surgical margins are close

Small-round-cell tumor differential

• if < 5 yrs. and there are small round cells think neuroblastoma or leukemia
• if approximately 10 years think eosinophilic granuloma
• if 10-30 yrs and there are small round cells think Ewing's
• if >30 yrs think lymphoma
• if > 50 yrs. and there are small round cells think myeloma

Giant cell tumour

Introduction

A benign but aggressive tumor of unknown origin that is usually found in the epiphysis of long bones  Age more common in females (unlike most bone tumors) ages 20-40 years (80% of giant cell tumors occur in patients older than age 20 years, with the peak incidence in the third decade of life) patient age/gender on previous OITE questions: 17F, 21M, 27F, 34F, 36F, 40M  Location 50% around knee (distal femur or proximal tibia), most common location  10% in sacrum and vertebrae (sacrum is most common site in axial skeleton)  distal radius is third most common location phalanges of the hand is also a very common location Malignant potential as primary malignant giant cell tumor metastasizes to lung in 2%  hand lesions have greater chance of metastasis secondary malignant giant cell tumor occurs following radiation or multiple resections of giant cell tumor Differential If multiple lesions (~1%) than rule out hyperparathyroidism

Symptoms

Presentation   pain referable to involved joint

Imaging

Radiographs lytic and destructive metaphyseal lesion that often extends into the epiphysis and often borders subchondral bone  may have cortical thinning with breakthrough Bone scan is very hot  MRI shows clear demarcation on T1 image between fatty marrow and tumor

Histology

Characteristic findings basic proliferating cell type is the mononucleur spindle-shaped stromal cell  hallmark Giant cells are numerous  nucleus of giant cell appears same as spindle-shaped stromal cells

Treatment

Operative extensive curettage with chemical cauterization (phenol), bone grafting and cementing  challenge of treatment is to remove lesion while preserving joint and providing buttress support to subchondral joint aggressive exterioration of overlying cortex is required  10-30% recurrence with curettage alone verses 3% with cementation hand lesion treatment is controversial if no cortical breakthrough treat with curettage and cementing if significant cortical breakthrough consider intercalary resection (with free fibular graft) vs. amputation radiation alone for inoperable lesions only leads to 15% malignant transformation

Chondrosarcoma

Introduction
Malignant chondrogenic lesions can occur in two forms primary chondrosarcoma which includes low-grade, high-grade, de-differenitated chondrosarcoma clear cell chondrosarcoma  mesenchymal chondrosarcoma  secondary chondrosarcoma arises from benign cartilage lesions including  osteochondroma (<1% risk of malignant transfomation) multiple hereditary exostosis (1-10% risk of malignant transfomation) enchondromas (1% risk of malignant transfomation) Ollier's disease (25-40% risk of malignant transfomation) Marfucci's (100% risk of malignant transfomation) Age & location typically, chondrosarcomas are found in older patients (40-75 yrs) there is a slight male predominance most common locations include the pelvis, proximal femur, scapula  tumor location is important for diagnosis as the same histology may be diagnosed as benign in the hand but malignant if located in the long bones Grade 85% of chondrosarcomas are grade 1 or 2 15% of chondrosarcomas are grade 3 or dedifferentiated chondrosarcoma  de-differentiated chondrosarcomas are high grade lesions which develop from low grade chondroid lesions and require more aggressive treatment including adjuvant chemotherapy Prognosis axial and proximal extemity lesions have a more aggressive course histologic grade correlates with survival Grade I: 90% survival Grade II: 60-70% survival Grade III: 30-50% survival De-differentiated chondrosarcoma: 10% survival increased telomerase activity in chondrosarcoma, as determined byreverse transcriptase-polymerase chain reaction (RT-PCR), has been shown to directly correlate with the rate of reccurence  Primary Chondrosarcoma sub-types Clear cell chondrosarcoma  malignant immature cartilaginous tumor accounting for <2% of all chondrosarcomas most common in 3rd and 4th decades of life commonly presents with insidious onset of pain  presents as an epiphyseal lesion and can be mistaken for low-grade chondroblastoma locally destructive with potential to metastasize  Mesenchymal chondrosarcoma chondrosarcoma variant which presents with a biphasic pattern of neoplastic cartilage with associated neoplastic small round blue cell component occurs in younger patients than typical chondrosarcomas may occur at several discontinuous sites at presentation and can occur in the soft tissues treatment includes neo-adjuvant chemotherapy followed by wide surgical resection

Symptoms

Presentation pain is the most common symptom may present with slowly growing mass or symptoms of bowel/bladder obstruction due to mass effect in the pelvis 50% of de-differentiated chondrosarcomas present with a pathologic fracture

Imaging

Radiographs lytic or blastic lesion with reactive thickening of the cortex  low-grade chondrosarcomas have a similiar appearance to enchondromas with additional cortical thickening/expansion and endosteal erosion   high-grade chondrosarcomas are less well defined on plain radiographs and frequently present with cortical destruction and a soft tissue mass intra-lesional "popcorn" mineralization  may be seen described as rings, arcs, and stipples of mineralization de-differentiated chondrosarcomas radiographically show a lower grade chondroid lesion with superimposed highly destructive area consistentwith the high grade transformed dedifferentiated chondrosarcoma  MRI or CT helpful to determine cortical destruction, marrow involvement, and the soft tissue involvement  Bone scan is usually very hot in all grades of chondrosarcoma

Histology

Chondrosarcoma needle biopsy is not indicated for cartilage tumors due to difficulties with diagnosis it is often difficult to determine malignancy based on histology alone chararcteristic histology low-grade chondrosarcomas show few mitotic figures with a bland histologic appearance and associated enlarged chondrocytes with plump multinucleated lacunae  high-grade chondrosarcomas have a hypercellular stroma consisting of characteristic "blue-balls" of a cartilage lesion which permeate the bone trabeculae  enchondromas of hand, Ollier's disease, Maffucci's disease, periosteal chondromas, and chondrosarcoma may all have similar histology De-differentiated chondrosarcomas characterized by a bimorphic histology low grade chondroid component high grade spindle cell component (similiar histology to osteosarcoma, fibrosarcoma, MFH)

Treatment

Operative intra-lesional curettage  indications Grade 1 lesions  treatment of grade 1 lesions located in the pelvis or axial skeleton is controversial many authors recommend wide excision of all chondrosarcomas (even grade 1) if located in the pelvis wide surgical excision  indications grade 2 or 3 lesions some say grade 1 lesions in pelvis historically, there is no significant role for radiation or chemotherapy in typical intramedullary chondrosarcoma  wide surgical excision combined with multi-agent chemotherapy  indications high-grade de-differentiated chondrosarcoma mesencymal chondrosarcoma

Telangiectatic osteosarcoma

Introduction

Occur in same location as ABC (look similar radiographically as well)

Symptoms

Presentation 25% present with pathologic fracture

Imaging

Radiographs lytic, destructive, and expansile lesion Bone scan hot

Histology

Characterized by few cellular components (those present have malignant characteristics) not as much osteoid as intramedullary osteosarcoma  lakes of blood mixed with malignant cells (not in ABC)

Treatment

Same as intramedullary osteosarcoma   multi-agent chemotherapy and limb salvage resection chemotherapy preoperative chemotherapy given for 8-12 weeks followed by maintenance chemotherapy for 6-12 months after surgical resection 98% necrosis with chemo is good prognostic sign expression of multi-drug resistence (MDR) gene portends very poor prognosis cells can pump chemo out of cell present in 25% of primary lesions and 50% of metastatic lesions surgical resection trend towards limb salvage whenever possible

Prognosis

More chemosensitive but same survival as intramedullary osteosarcoma

Parosteal Osteosarcoma

Introduction

A low grade osteosarcoma Age & location more common in females, age 30-40 previous exam question ages: 75, 74 yrs occurs on surface of metaphysis of long bones most common sites include posterior distal femur, proximal tibia, and proximal humerus marrow invasion in 25%

Symptoms

Presentation often presents as a painless mass can limit joint motion (knee)

Imaging

Radiographs heavily ossified, lobulated mass arising from cortex (appears as if sticking to cortex) Bone scan mandatory and always hot CT chest mandatory to rule out pulmonary mets MRI mandatory to determine soft tissue involvement and skip lesions

Histology

Characteristic histology regularly arranged normal osseous trabeculae  slightly atypical spindle cells within trabeculae cartilage is often present and may take the form of a cartilage cap Pathologist ocassionally mistakes for fibrous dysplasia

Treatment

Operative wide local surgical excision often curative chemotherapy not indicated unless there is a high grade component

Prognosis

95% long term survival when local control has been achieved dedifferentiation is a poor prognostic factor

Groups & Differentials

Fibrous dysplasia (similar on histology, but xrays are different) Myositis Ossificans Traumatica (juxtaposed to bone) Osteochondral exostosis (shares cortex with bone) Developmental defect at insertion of adductor magnus