Chromophobe renal cell carcinoma vs Oncocytoma

Distinguishing between oncocytoma and the eosinophilic variant of chromophobe renal cell carcinoma is a significant and relatively frequent problem for surgical pathologists. This is my experience of just such a case.

Macroscopically radical nephrectomy showed a well circumscribed upper pole tumour with a firm homogenous tan/brown appearance upto 40mm. There was no evidence of cystic change or necrosis. Typically both chromophobe and oncocytoma have a similar appearance as described above – a well circumscribed tumour with homogenous tan/brown appearance whilst a oncytoma may also show a central stellate scar.

On microscopy chromophobe characteristically shows large polygonal cells with prominent cell membranes (with an embossed appearance), Nuclei are small with a wrinkled appearance and there is often a prominent perinuclear halo. Oncocytomas characteristically show solid compact nests, acini, tubules or microcysts of oncocytes which are large polygonal cells with dense eosinophilic cytoplasm round and regular round nuclei.

Histologically my case showed features of both with architecturally areas showing nests and acini typical of oncocytoma however more solid areas with large polygonal cells with prominent cell membranes however lacking perinuclear halos and a small wrinkled appearance.

Immunohistochemistry for distinguishing conventional RCC, chromophobe and oncocytoma:

RCC, CD10 and Vimentin are positive and CD117 neg and E-cadherin neg in conventional RCC, compared to chromophobe & oncocytoma which tend to be positive for CD117 and e-cadherin.

CK7 is useful in the distinction of chromophobe/oncocytoma with chromophobe tending to show a more diffuse positivity whilst with oncocytoma a patchy staining.

CD15 is thought to be positive in oncocytoma and neg in chromophobe. And oncocytoma tends to show stronger staining with ecadherin than chromophobe.

This case showed positivity to CD117, ecadherin and CD15 and negativity to vimentin and CK7 favouring a diagnosis of oncocytoma.

Prognosis: Oncocytoma is thought to be an entirely benign entity. Chromophobe renal cell carcinoma has been shown to have a significantly better prognosis than conventional renal cell carcinoma.

References:

Boswick. Urologic Surgical Pathology

WHO classification of tumours: Tumorus of the Urinary System and Male Genital Tract.

 

 

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Gleason Grading

The literature can be confusing about differences in the grading based on whether it’s a radical prostatectomy or TRUS biopsy and whether to go with the most common or the highest grade and the use of a tertiary grade.

This appears to be the current approach where I work:

  1. Grading for transrectal ultrasound guided biopsies and radical prostatectomies are the same
  2. The most prevalent and second most prevalent grade are added up (eg: 3+4, 4+3 however there does not appear to be a clinical difference in how these are managed)
  3. The tumour needs to show at least 5% of a grade of tumour to for it to be included in the grading including the tertiary grade
  4. The tertiary grade should be used only rarely. When all 3 grades are present. Then the most prevalent and the highest grade is used with the remaining going into the tertiary. (eg: 3+5=8 with tertiary 4 when all 3 present equally in a core bx)
  5. More likely to have a tertiary grade in a prostatectomy as you see much more prostatic tissue.
  6. Grade 3 well formed glands you can draw around, Grade 4 when cribriform or fused glands, Grade 5 when single glands, solid areas or glands associated with comedo type necrosis

References:

RCPath dataset for reporting prostatic carcinoma.

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LAMN : low grade appendiceal mucinous neoplasms

A controversial area and I refer you to the references.

However for practical purposes LAMN (low grade appendiceal mucinous neoplasms) are a distinct subset of appendiceal mucinous tumours that lack usual forms of destructive invasion into the appendiceal wall. Histologically the normal appendiceal mucosa is replaced with a villiform mucinous epithelial proliferation.

Despite the bland histology of the mucinous epithelium these have the propensity to spread to the peritoneum and ovaries, frequently progressing to the clinical syndrome known as pseudomyxoma peritonei and often results in the demise of the patient. PP results in death of 50% of patients from bowel obstruction.

References:

Appendiceal mucinous neoplasms. Controversial Issues. Misdraji J., Arch Pathol Lab Med – Vol 134, June 2010

 

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Odontogenic Cysts

Inflammatory:

Periapical cyst (Radicular cyst): When the pulp of the tooth undergoes necrosis due to caries or trauma a granulation tissue response known as a peri-apical granuloma may develop. This can stimulate proliferation of epithelium (Malassez rests) near the tooth to proliferate and become cystic forming a periapical cyst. Ocassionally the epithelium will contain linear and hairpin-shaped hyaline bodies known as Rushton bodies.

Developmental:

Dentigerous cyst: Before tooth formation if fluid accumulates between reduced enamel epithelium (dental follicle epithelium) and the crown of the tooth. Varible histo appearances. Cyst lined by a thin flattened non keratinising epithelium. Loose connective tissue stroma with scattered odontogenic epithelial rests. These may undergo dystrophic calcification.

Keratocystic Odontogenic Tumour/Odontogenic keratocyst: Higher rate of recurrence. Assoc with nevoid basal cell carcinoma syndrome (Gorlin’s syndrome). Cyst lined by stratified squamous epithelium of uniform thickness wtih desquamated keratin within the cyst lumen. Epithelial lining shows a palisaded cuboidal to columnar basal layer and a corrugated parakeratinising surface. No granular cell layer.

Orthokeratinising Odontogenic cyst: (Important to differentiate from KOT) Cyst lined by stratified squamous epithelium with orthokeratosis. Granular cell layer present. No palisaded columnar basal layer or corrugated/wavy layer of keratin.

Gingival (alveolar) cyst of the newborn: Common, multiple small pearl like nodules on the alveolar ridge. Stratified squamous lining with desquamated parakeratin in lumen. (From remnants of dental lamina epithelium)

Gingival cyst of the adult: Uncommon. Cyst with a thin attenuated lining. (From remnants of dental lamina epithelium).

Lateral periodontal cyst (Botryoid Odontogenic cyst): Lined by a thin layer of epithelium with focal nodular thickening. Radiologically presents as a well circumscribed, unilocular radiolucency located lateral to the roots of vital teeth.

Calcifying odontogenic (Gorlin) cyst/ Calcifying cystic odontogenic tumour: Given apparent neoplastic potential discussed under tumours in text. Aka Dentinogenic ghost cell tumour (in WHO text). Well defined unilocular radiolucency with scattered radioopacities. Proliferation of odontogenic epithelial cells associated with the cystic lumen. Palisaded basal cell layer of the lesional epithelium and the ghost cell change with areas of dystrophic calcification.

Glandular odontogenic cyst: Stratified squamous epithelial lining that exhibits ciliated columnar cells on the surface. The epithelium contains prominent gland like spaces that are also lined by columnar cells.

Eruption cyst: Fluid/haemorrhage between dental follicle and crown assoc with a erupting tooth. Esp in children.

Carcinoma arising in odontogenic cysts

References:

Gnepp. Diagnostic Surgical Pathology of the Head and Neck.

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Salivary Gland Neoplasms

Pleomorphic Adenoma: A well defined encapsulated nodule consisting of sheets and nodules of cytologically bland ductal and plasmacytoid elements. (epithelial-myoepithelial elements). There are occasional foci of duct formation. This is arranged in a myxofibrillary matrix.

  • Completeness of excision
  • Evidence of atypia/malignancy (?carcinoma ex pleomorphic adenoma)
  • Adjacent salivary tissue? obstructive changes
  • Intraparotid lymph nodes

Warthin Tumour: An encapsulated tumour on showing lymphoid stroma, cystic change and intraluminal papillary epithelial projections. The papillae have a bilayer of oncocytic epithelium overlying a lymphoid stroma with germinal centers.

Acinic cell carcinoma: A slowly enlarging mass in the parotid region with serous acinar cell differentiation. Acinar cells are large, polygonal cells with lightly basophilic granular cytoplasm and round eccentric nuclei. Cytoplasmic zymogen granules DPAS positive. Vacuolated cells contain clear cytoplasmic vacuoles.

Adenoid cystic carcinoma: Basaloid tumour consisting of epithelial and myoepithelial elements. Architecuturally may be tubular, cribriform or solid. Cribriform is the most common with mucopolysaccaride filled spaces. Perineural invasion common. May invade bone extensively. Duct cells +ve for CD117, basal cells for actin S100.

Basaloid neoplasms differential diagnosis:

  • Basal cell adenoma
  • Epithelial-myoepithelial carcinoma
  • Basaloid squamous cell carcinoma
  • Basal cell adenocarcinoma
  • Adenoid cystic carcinoma
  • Polymorphous low grade adenoca

Mucoepidermoid carcinoma: Characterised by squamoid (epidermoid), mucus producing and cells of intermediate type. Architecture varies. Positive for mucicarmine/alcian blue. Grades low, intermediate & high – cystic component<20%, neural invasion, necrosis, >4mitoses/10hpf, anaplasia.

Mucoepidermoid carcinoma 10144013

Polymorphous low grade adenoca: A relativelly indolent malignancy, most cases arising from the minor salivary glands. Althought the tumour cells tend to be cytologically bland and monomorphic, it can form a wide variety of archictural patterns and infiltrative growth pattern.

Lymphoepithelial carcinoma: Undifferentiated carcinoma accompanied by a prominant non-neoplastic lymphoplasmacytic infiltrate. High incidence in China where EBV is implicated as an aetiological agent.

Basal cell adenoma: Benign basaloid appearance of tumour cells and absence of myxochondroid stroma. Tubular type and membranous type (prominent hyaline material)

Oncocytoma: Benign tumour composed exclusivelly of large epithelial cells with characteristic bright eosinophilic granular cytoplasm.

References:

WHO classification of tumours. Head and Neck tumours.

Robbins and Cotrans. Pathological Basis of Disease.

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Nomenclature clarification for serrated lesions and adenomas

Lesions with a tufted appearance are described as having a serrated architecture.

Hyperplastic polyps – Benign polyps with a serrated architecture – No follow up required.

Adenomas – Tubular, Villous and Tubular-Villous. Show low grade dysplasia. Follow up as per protocol.

  • Mixed Polyps – Hyperplastic polyps with dysplasia – FU as per adenoma
  • Traditional serrated Adenoma – Adenomas with a serrated architecture.

Sessile serrated lesions (polyps & adenomas) – Serrated lesions with an unusual architecture. 1) Horizontally orientated, boot shaped deep crypts, 2) Serration down to crypt base. Usually right sided, Large sessile poorly defined lesions, Assoc with MLH1. Sessile serrated lesions – FU for recurrence 3 yearly. Sessile serrated adenomas – as for Adenomas

Serrated Adenocarcinoma – Majority arise in traditional serrated adenomas and have a poor prognosis. 20% arise in sessile serrated lesions have a good prognosis.

New guidelines (2012) for polypectomy surveillance after colonoscopy, see:  http://gastroenterology.jwatch.org/cgi/content/full/2012/928/6

“A new set of recommendations for surveillance intervals after resection of serrated lesions. In these recommendations, patients with a small sessile serrated polyp (<10 mm) with no dysplasia should have repeat colonoscopy in 5 years. Patients with a sessile serrated polyp ≥10 mm, a sessile serrated polyp with dysplasia, or a traditional serrated adenoma should undergo repeat colonoscopy in 3 years. Serrated polyposis syndrome should be followed at 1 year, though subsequent examinations that identify a decreasing polyp burden can be followed by expanded intervals.”

Reference:

Williams G., Serrated lesions. BSCP presentation

Bettington et al. The serrated pathway to colorectal carcinoma: current concepts and challenges. Histopathology 2013. 62, 367-386.

Atkin et al. Surveillance guidelines after removal of colorectal adenomatous polyps. Gut. 2002; 51 (supplement V): V6-v9.

Lieberman DA et al. Guidelines for colonoscopy surveillance after screening and polypectomy: A consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2012 Sep; 143:844.

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Poorly Differentiated Carcinoma of the Colon

The differential diagnosis of poorly differentiated carcinoma of the colon include:

  • Poorly differentiated adenocarcinoma
  • Medullary carcinoma of the colon &
  • Large cell neuroendocrine carcinoma

Medullary carcinoma will usually have sheets, nest or trabecular of small to medium sized cells with a pushing border and a lymphocytic infiltrate with Crohn’s like lymphoid aggregates at the tumour edge. Negative for neuroendocrine markers. Associated with microsatellite instability.

Poorly differentiated adenocarcinoma may show areas with glands.

Neuroendocrine carcinoma – positivity to CD56, synaptophysin & chromogranin.

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