Other surgical pathology

Cornea

Author: Mikael Häggström

Comprehensiveness

On this resource, the following formatting is used for comprehensiveness:

• Minimal depth
• (Moderate depth)
• ((Comprehensive))

Gross processing

• Inspect
• Measure
• Serially section in 3-4 mm wide slices.

Example gross report:

(Labeled: ___. The specimen is received in formalin and consists of an) << opaque / translucent>> corneal disc measuring __ cm in diameter and __ cm in thickness. The specimen is serially sectioned and entirely submitted for microscopic examination in one cassette.

Microscopic examination

Corneal subepithelial acute inflammation, seen as the presence of neutrophils, as well as chronic inflammation, seen as plasma cells and lymphocytes. There is an associated neovascularization. Bowman's membrane is disrupted. The findings are non-specific.

Look for integrity of Bowman's and Descemet's membranes.

For corneal opacities, look for the most common causes, which generally manifest as:

• Inflammation and edema
• Traumatic injury

Reporting

Example:

(Right eye cornea, excision: Cornea with) patchy acute and chronic inflammation, nonspecific, with disrupted Bowman's membrane and associated neovascularization.

Main page

• Main page of Patholines

Urinary bladder

Author: Mikael Häggström

Urinary bladder biopsy

Usually performed as a transuretral resection of the bladder (TURB).

Gross reporting of transurethral resections

• Generally submit all material. (It may be sufficient to submit representative sections that include the muscular layer, if grossly identified. Yet, many departments require submission of the entire specimen regardless, so if unsure, that is the safe choice.)
• If transported or processed together with other cases, put the samples in thin-mesh cassettes or tissue bags to limit contamination.

Example report:

Container A. Labeled "bladder tumor". The specimen is received in formalin and consists of multiple fragments of tan-gray, friable soft tissue measuring about __ x __ x __ cm in aggregate. The specimen is entirely submitted for microscopic examination in __ cassettes.

Microscopy

Mainly look for urothelial carcinoma (also called transitional cell carcinoma), which constitutes 95% of bladder cancers.

• 

  Low grade urothelial carcinoma: Urothelium is thickened but only slightly atypical and has maintained polarity.

• 

  High grade urothelial carcinoma: Loss of polarity and severe abnormal cytology.

• 

  In contrast, an inverted urothelial papilloma has smooth surface with minimal to absent exophytic component, is well circumscribed with smooth base, and has no obvious infiltration and no/minimal cytologic atypia.

Other possibilities:

• 

  Squamous cell carcinoma of the urinary bladder. Further information: Urothelial versus squamous cell carcinoma

• 

  Radiation cystitis with atypical stromal cells (“radiation fibroblasts”), edema and inflammation. Check whether the patient has received radiation before making the diagnosis.

• 

  Edema (clear spaces of both the lamina propria and cytoplasm of multiple urothelial cells), which is non-specific.

Main page

• Main page of Patholines

Urine cytology

Author: Mikael Häggström

Normal urothelial cells.

Clinical information

It is not necessary to look through more than readily available reports from previous urine cytologies.

Evaluation

Mainly look for:

• 

  Reactive urothelial changes, Pap stain, showing urothelial cells with enlarged nuclei but a nucleus-cytoplasm ratio of less than 0.5. There are bacteria, as well as an inflammatory response of neutrophils, providing a cause for the changes. Can be reported as "Benign urothelial cells, neutrophils and bacteria".

• 

  High-grade urothelial carcinoma. Cytologic diagnosis of high-grade urothelial carcinoma requires > 10 cells with high N/C ratio, irregular chromatin pattern and hyperchromatic nuclei (Pap stain).

• 

  Distinguish urothelial carcinoma from decoy cells, which are virally infected epithelial cells (Pap stain).

• 

  Also report the presence of red blood cells (here seen compared to benign urothelial cells, Pap stain).

The Paris System for reporting urine cytology, version 2.0.

The N/C ratios apply to the finding of any cells meeting the criteria, and not the average among atypical cells (in the majority of obviously positive cases, N/C/ratio averages 0.5). When there are obvious features of malignancy, there is no need to hunt for cells that fulfil all criteria to make such diagnosis.

• 

  Nuclear/cytoplasmic ratios.

• 

  Fibrovascular cores weakly indicate a urothelial neoplasm, but can be present in all Paris System categories.

Main page

• Main page of Patholines

Digit

Author: Mikael Häggström
For an amputated toe or finger:

Comprehensiveness

On this resource, the following formatting is used for comprehensiveness:

• Minimal depth
• (Moderate depth)
• ((Comprehensive))

Other legend

<< Decision needed between alternatives separated by / signs >>
{{Common findings / In case of findings}}
[[Comments]]
Link to another page

Intitial processing

• Measure length and average diameter
• Determine the anatomic location of the cut (proximal to the distal phalanx, middle phalanx, metatarsal phalangeal joint etc).
• Look at soft tissue margins whether they look viable or necrotic.
• Look at the skin surface. For any lesion such as ulcerated or necrotic one, measure the distance to the nearest soft tissue margin.
• Ink the surgical margins differently for soft tissue and bony margin(, including if the bony margin is a joint surface ("cartilaginous margin").)

Amputated finger after longitudinal split.

• Split the digit longitudinally, either in the midline or at the closest margin between any ulcer and the soft tissue margin.
• Let the tissue fix in formalin and then use a relatively strong decalcifying agent, usually at least 5-6 hours.

Tissue selection

Sections for microscopy are taken as follows:

For amputations disarticulated at the joint:

• Perpendicular sections of the articular cartilage and adjacent bone. State which bone in key of sections.

For amputations resected by cutting across bone:

• Ink the bone at the proximal margin, submit perpendicular section of bony margin.

Gangrene and/or suspected osteomyelitis:

• Submit cross sections of each bone with associated ulcer and/or gangrene if appropriate, generally sagittal/longitudinal. Attempt to include the longitudinal distance from potential osteomyelitis to the proximal bony/cartilaginous margin.
• Skin and soft tissues at proximal margin.

• If margin is close to gangrene: perpendicular sections
• If far, submit en face

• If you receive a separate thin or discoid bone slice, it is generally an additional bone margin. Preferably, have this decalcified and processed promptly, so that it may be used to make a preliminary report as to whether it is involved even before the main specimen is processed.

• 

  Contiguous longitudinal sections from a finger with suspected osteomyelitis.

• 

  Finger with en face soft tissue margins because of no proximity to gangrene.

At least if osteomyelitis is suspected, ink all proximal (and/)or distal cut surfaces (differentially) of each slice, so that the pieces can be oriented, and the distance between osteomyelitis and the surgical margin can be estimated. The exception is where pieces can most definitely be anatomically oriented, such as the presence of a nail distally.

Gross report

Example:

(A. Labeled - ___. The specimen is received in formalin and consists of an amputated toe/finger.) The digit measures ___ cm in length and ___ cm in average diameter. The digit is resected ___ [[location]]. {{The proximal ___ cm of the specimen is not covered by skin and soft tissue.}} The skin and soft tissue margins appear <viable / necrotic>. The skin surface of the digit appears ___ {{and displays an (ulcerated/necrotic/gangrenous) lesion, cm from the cutaneous margin}}. The nail is <color/thickened/absent/necrotic>. The soft tissue surgical margin is inked blue [[for example]], and the <<bony surgical / cartilaginous>> margin of the ___ [[specific bone involved]] is inked green [[for example]]. On cut sections, the bone subjacent to the ulcer shows no gross abnormalities. Representative sections are submitted for microscopic examination in ___ cassettes following decalcification. Key to sections: Longitudinal section through distal phalanx Longitudinal section through proximal phalanx, including <<bony surgical / cartilaginous>> margin Skin and soft tissues at proximal margin, submitted en face

Microscopic examination

Mainly, detect the presence of:

• 

  Osteomyelitis, mainly by neutrophils in the stroma. Further information: Osteomyelitis

Microscopic report

Example:

(A. Left third toe, amputation:) Toe with ulcer, gangrene and osteomyelitis. Osteomyelitis involves the distal phalanx, middle phalanx and proximal phalanx. Osteomyelitis is 2.0 cm from the proximal articular surface of the proximal phalanx. (The skin and soft tissue at the surgical margin appear viable.)

Bone

Grossing

To submit slides for microscopy, generally gross as follows:

• Split the bone in the plane of interest for microscopy slides.
• Fix the bone in formalin.
• Perform decalcification of the specimen. First, generally take at least a small piece to be kept separately in formalin, in case the main specimen becomes necrotic, so that you have at least one more chance to decalcify it more lightly. If the order and/or history is suspicious for metastasis, try to sample a part of the specimen that is soft enough to not need decalcification (to avoid the risk that decalcification will impair later immunohistochemistry or other testing).
• Take the sections of interest.

Microscopic evaluation

Look for any of the following:

• 

  Acute osteomyelitis: Numerous neutrophils in the stroma.

Metastasis

Highly suspicious prostate adenocarcinoma metastasis can be confirmed with NKX1, TTF1 and CDX2.

Main page

• Main page of Patholines

Pituitary

Author: Mikael Häggström

Microscopic evaluation

• Look for cellular expansions, which in the anterior pituitary confers a loss of normal cellular heterogeneity.
• If present, distinguish it as hyperplasia or neoplasia. If uncertain, by using reticulin immunohistochemistry, hyperplasia will show a preserved reticulin meshwork, whereas pituitary adenomas have disruption of it.

• For adenomas, unless otherwise indicated by the medical history, will generally by definition be of the silent type. Basophilic or acidophilic staining may give a clue about the subtype, but immunohistochemistry is generally required.

• 

  Normal cellular heterogeneity of the anterior pituitary. Nuclear pleomorphism, like the large nucleus of the chromophobe, is a normal finding in this location.

• 

  Incidences of silent pituitary adenomas.

• 

  A silent gonadotroph pituitary adenoma which is in this case is eosinophilic (contrary to normal, basophilic, gonadotroph cells).

Microscopy report

In normal autopsy:

Adenohypophysis and neurohypophysis with no focal changes.

Main page

• Main page of Patholines

Brain/meningeal tumor

Intraoperative consultation of brain tumor fragments

Preparation

If you are expecting a brain/meningeal tumor, look at any radiology to find out what is the suspected diagnosis or differential diagnoses. A connection to the dura raises the suspicion of a meningioma. Multiple tumors raises the suspicion of metastasis or lymphoma.

Grossing

Resected fragments of a brain tumor, and in this case the very dark appearance supports a diagnosis of metastatic pigment-forming melanoma.

Measure the size of the specimen in 3 dimensions.

Histopathology of a typical WHO grade 1 meningioma, H&E stain. It is of the meningothelial histologic type, which is the most common meningioma type. It shows its typical findings:
- A woven architectural pattern
- Psammoma bodies (spheroid calcifications)
- Syncytial cells (having indistinct cell membranes) with eosinophilic (pink) cytoplasms
- Round uniform nuclei
- Whorls (concentric cell arrangements)

Squash prep

Remove a drop-size sample, place it on a glass-slide, then gently smear it out with another glass slide, followed by applying a fixative solution and staining with H&E.

Evaluation

The most common primary brain tumors are:

• Gliomas (50.4%)
• Meningiomas (20.8%)
• Pituitary adenomas (15%)
• Nerve sheath tumors (10%)

Also look into the patient's history for past cancers that may have metastasized to the brain.

The location, younger vs older age, as well as the overall pattern provide the main differential diagnoses:

Location and younger vs older age

Main brain tumors

Location	Child or young adult	Older adult
Cerebral, supratentorial	Ganglioglioma, dysembryoplastic neuroepithelial tumor (DNET), pleomorphic xanthoastrocytoma (PXA), ependymoma, atypical teratoid/rhabdoid tumor (AT/RT), CNS embryonal neoplasms	Glioblastoma, infiltrating astrocytoma (grades II-III), oligodendroglioma, metastasis, lymphoma, infection
Cerebellar, infratentorial, fourth ventricle	Pilocytic astrocytoma, medulloblastoma, ependymoma, choroid plexus papilloma, atypical teratoid/rhabdoid tumor (AT/RT)	Metastasis, hemangioblastoma, choroid plexus papilloma, subependymoma
Brainstem	Pilocytic astrocytoma, diffuse midline glioma	Astrocytoma, glioblastoma, diffuse midline glioma, metastasis
Spinal cord (intramedullary)	Ependymoma, pilocytic astrocytoma, diffuse midline glioma, myxopapillary ependymoma, drop metastasis	Ependymoma, astrocytoma, diffuse midline glioma, myxopapillary ependymoma (filum terminale), paraganglioma (filum terminale)
Spinal cord (extramedullary)	Meningioma, schwannoma, metastasis, melanocytoma, melanoma	Schwannoma, meningioma, melanocytoma, melanoma, malignant peripheral nerve sheath tumor (MPNST)
Spinal cord (extradural)	Bone tumor, meningioma, abscess, vascular malformation,	Herniated disk, lymphoma, abscess, metastases,
Extra-axial, dural, leptomeningeal	Leukemia/lymphoma, Ewing sarcoma, rhabdomyosarcoma, disseminated medulloblastoma, diffuse leptomeningeal glioneuronal tumor (DLGNT),	Meningioma, solitary fibrous tumor, metastasis, lymphoma
Sellar/infundibular	Pituitary adenoma, craniopharyngioma, Rathke cleft cyst, pituicytoma, Langerhans cell histiocytosis (LCH), germ cell tumors	Pituitary adenoma, craniopharyngioma, Rathke cleft cyst, pituicytoma, meningioma, metastasis, chordoma
Suprasellar, hypothalamic, optic pathway, third ventricle	Germ cell tumors, craniopharyngioma, pituitary adenoma, optic glioma, Langerhans cell histiocytosis (LCH)	Colloid cyst, craniopharyngioma, chordoid glioma
Pineal	Germ cell tumors, pineocytoma, pineoblastoma, pineal cyst	Pineocytoma, pineal cyst, pineal parenchymal tumors of intermediate differentiation (PPTID)
Thalamus	Pituitary adenoma, diffuse midline glioma	Diffuse midline glioma, glioblastoma, lymphoma
Lateral ventricle	Central neurocytoma, subependymal giant cell astrocytoma (SEGA), choroid plexus papilloma/carcinoma, meningioma	Central neurocytoma, subependymal giant cell astrocytoma (SEGA), choroid plexus papilloma/carcinoma, subependymoma, meningioma
Nerve root, paraspinal	Neurofibroma, schwannoma, malignant peripheral nerve sheath tumor (MPNST)	Neurofibroma, schwannoma, MPNST, lymphoma, meningioma
Cerebellopontine angle	Schwannoma, Choroid plexus papilloma, atypical teratoid/rhabdoid tumor (AT/RT)	Schwannoma, meningioma, epidermoid cyst, choroid plexus papilloma, endolymphatic sac tumor

Overall patterns

Parenchymal Infiltrate with hypercellularity

Hypercellular infiltrate but intact architecture:

• Diffuse gliomas
• Diffuse large B cell lymphoma of the CNS
• Angiocentric glioma
• Inflammatory/infectious processes
• Active demyelinating diseases
• Histiocytic disorders (e.g., Erdheim-Chester disease)
• Infarcts
• Metabolic/toxic diseases
• Reactive gliosis

Solid mass

A sharply demarcated lesion:

• Metastases
• Ependymoma
• Subependymoma
• Subependymal giant cell astrocytoma (SEGA)
• Neurocytoma
• Pineal parenchymal tumor
• Embryonal neoplasm
• Choroid plexus tumor
• Hemangioblastoma
• Paraganglioma
• Pituitary adenomas
• Astroblastoma
• Chordoid glioma of the 3rd ventricle

Solid and infiltrative process

Mostly solid, but with ill-defined margin towards adjacent brain tissue:

• Pilocytic astrocytoma
• Pilocytic xanthoastrocytoma
• Glioblastoma/gliosarcoma
• Ganglioglioma
• Dysembryoplastic neuroepithelial tumor
• Embryonal neoplasms (e.g., Medulloblastoma)
• Choroid plexus carcinoma
• Germ cell tumors
• Craniopharyngioma
• Diffuse large B-cell Lymphoma
• Sarcoma
• Histiocytic tumor
• Abscess/infection

Destructive/necrotic process

Extensive necrosis and destruction of normal tissue:

• Infarcts
• Glioblastoma
• Radiation necrosis/treatment effect
• Infection
• Vasculitis
• Lymphoma
• Severe demyelinating disease
• Metabolic/toxic disease

Vasculocentric

Centered around blood vessels:

• Diffuse large B-cell lymphoma
• Intravascular lymphoma
• Angiocentric glioma
• Ependymoma
• Vasculitis
• Demyelinating diseases
• Amyloid angiopathy
• Arteriosclerosis
• Vascular malformations
• Infection
• Sarcoidosis
• Thromboembolic disease

Extra-axial mass

Outside brain or spine

• Meningioma
• Solitary fibrous tumor/hemangiopericytoma
• Hemangioblastoma
• Peripheral nerve sheath tumors
• Metastasis
• Melanocytoma/melanoma
• Paraganglioma
• Pituitary adenoma
• Sarcoidosis
• Infection
• Bone tumors
• Histiocytic tumors
• Leukemia/lymphoma

Almost Normal Tissue

Only very subtle abnormalities:

• Nonrepresentative biopsy (they missed)
• Subtle diffuse glioma
• Cortical dysplasia and other malformations
• Mesial temporal sclerosis
• Intravascular lymphoma
• Encephalitis
• Cerebral malaria
• Microembolic disease
• Neurodegenerative diseases
• Metabolic/toxic disorders
• Reactive gliosis
• Cerebral edema
• Spongiotic/vacuolar changes
• Ischemic changes

Meningeal or cerebrospinal fluid infiltrate

Subarachnoid space expansion:

• Meningeal carcinomatosis
• Meningeal gliomatosis
• Meningeal melanocytis/melanomatosis
• Diffuse leptomeningeal glioneuronal tumor
• Metastatic medulloblastoma
• Leukemia/lymphoma
• Histiocytic disorders
• Meningitis
• Sarcoidosis
• Infection
• Collagen vascular disease

Meningioma

Microscopic evaluation

Histopathology of a typical WHO grade 1 meningioma, H&E stain. It is of the meningothelial histologic type, which is the most common meningioma type. It shows its typical findings:
- A woven architectural pattern
- Psammoma bodies (spheroid calcifications)
- Syncytial cells (having indistinct cell membranes) with eosinophilic (pink) cytoplasms
- Round uniform nuclei
- Whorls (concentric cell arrangements)

Look for the signs of both typical meningioma and main histological variants. On frozen sections, mention the presence of atypia/high-grade cells.

• 

  Histologic variants of meningioma, H&E stain

• 

  Meningioma, low-grade and high-grade. H&E stain.

On permanent sections, classify by WHO grade:

Meningioma grades

WHO Grade I	WHO Grade II	WHO Grade III
Benign	Atypical	Malignant
Meningiothelial Fibrous (fibroblastic) Transitional (mixed) Psammomatous Angiomatous Microcystic Secretory Lymphoplasmacyte-rich Metaplastic	Chordoid Clear Cell Atypical	Papillary Rhabdoid Anaplastic

Reporting

Example frozen section report:

A. Right frontal tumor: -Meningioma. Negative for atypia.

Example permanent section report:

A. Right frontal tumor: -Meningioma, WHO grade 1.