cytology cornucopia

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Cytology Cornucopia Cytology Cornucopia Teresa M Alasio Teresa M Alasio MD MD December 8, 2005 December 8, 2005 Bellevue Hospital – est. 1734

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A presentation on the cytology of a variety of lesions of the head and neck and breast. The intended audience is pathologists, cytopathologists, pathology residents and medical students.

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Page 1: Cytology Cornucopia

Cytology CornucopiaCytology Cornucopia

Teresa M Alasio MDTeresa M Alasio MD

December 8, 2005December 8, 2005

Bellevue Hospital – est. 1734

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Case 1Case 1

First hospital based ambulance service in the world established at Bellevue by Dr. Edward L. Dalton in 1869

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Patient HistoryPatient History

28 year old male28 year old male Retroperitoneal mass, 6cmRetroperitoneal mass, 6cm CT guided aspiration biopsy CT guided aspiration biopsy

performedperformed

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ImmunohistochemistryImmunohistochemistryPan Keratin Cam 5.2

AFP PAS

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Summary of IHCSummary of IHC

PositivePositive AFPAFP AE1/AE3AE1/AE3 CAM 5.2CAM 5.2

PAS +PAS +

NegativeNegative PLAPPLAP HCGHCG CD 30CD 30 EMAEMA CK 7CK 7 CK 20CK 20 VimentinVimentin

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Cytologic InterpretationCytologic Interpretation Positive for malignancyPositive for malignancy Non-seminomatous germ cell tumorNon-seminomatous germ cell tumor Poorly differentiated tumor composed of Poorly differentiated tumor composed of

epithelial cells with high-grade nuclei and epithelial cells with high-grade nuclei and areas of necrosisareas of necrosis

Cells are positive for AE1/AE3, CAM 5.2, AFP Cells are positive for AE1/AE3, CAM 5.2, AFP by immunohistochemistryby immunohistochemistry

HCG, PLAP, CD30, CK 7, CK 20 EMA and HCG, PLAP, CD30, CK 7, CK 20 EMA and Vimentin are negative. Vimentin are negative.

Scattered intracytoplasmic hyaline inclusions Scattered intracytoplasmic hyaline inclusions are positive with PAS stain.are positive with PAS stain.

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Cytologic InterpretationCytologic Interpretation

Immunostaining pattern and Immunostaining pattern and morphology are consistent with a morphology are consistent with a yolk sac tumoryolk sac tumor

High grade nuclei and sheet-like High grade nuclei and sheet-like growth pattern are suggestive of growth pattern are suggestive of an embryonal carcinoma an embryonal carcinoma component, although CD 30 is component, although CD 30 is negativenegative

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Follow-upFollow-up

Left orchiectomy specimen arrived Left orchiectomy specimen arrived in surgical pathology one week in surgical pathology one week later…later…

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Surgical Pathology Surgical Pathology InterpretationInterpretation

Intratubular germ cell neoplasia, Intratubular germ cell neoplasia, multifocalmultifocal

Entire specimen was submitted for Entire specimen was submitted for histologic examinationhistologic examination

In addition…In addition…

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Extragonadal GCT Extragonadal GCT (EGGCT)(EGGCT)

Extragonadal germ cell tumors are rare Extragonadal germ cell tumors are rare and account for a small percentage of all and account for a small percentage of all germ cell tumors, 1-4%germ cell tumors, 1-4%

Can arise anywhere, but are typically Can arise anywhere, but are typically found in the midline where they present as found in the midline where they present as retroperitoneal, mediastinal or pineal massretroperitoneal, mediastinal or pineal mass

Important to actively search for and Important to actively search for and exclude testicular pathologyexclude testicular pathology

Systemic chemotherapy is most commonly Systemic chemotherapy is most commonly used treatment for these tumorsused treatment for these tumors

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Extragonadal GCTExtragonadal GCT

Fossa, et al. 2003. “Testicular Fossa, et al. 2003. “Testicular carcinoma in situ in patients with carcinoma in situ in patients with extragonadal germ cell tumors: the extragonadal germ cell tumors: the clinical role of pretreatment biopsy” clinical role of pretreatment biopsy” Annals of Oncology, 14: 1412-1418.Annals of Oncology, 14: 1412-1418.

Approximately 1/3 of patients with Approximately 1/3 of patients with EGGCT present with testicular CIS, EGGCT present with testicular CIS, predominantly those with a predominantly those with a retroperitoneal tumorretroperitoneal tumor

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Extragonadal GCT and Extragonadal GCT and IGCNIGCN

Scholz, et al. 2002. “Extragonadal Scholz, et al. 2002. “Extragonadal retroperitoneal germ cell tumor: retroperitoneal germ cell tumor: evidence of origin in the testis” evidence of origin in the testis” Annals Annals of Oncologyof Oncology 13:121-124. 13:121-124.

Proposed that retroperitoneal GCTs Proposed that retroperitoneal GCTs should be considered as metastases of should be considered as metastases of a viable or burnt out testicular cancer a viable or burnt out testicular cancer until proven otherwiseuntil proven otherwise

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Case 2Case 2

First school of nursing in the nation opened at Bellevue in 1873

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Patient HistoryPatient History

31 year old female31 year old female 3 weeks post partum3 weeks post partum Clinical symptoms of abdominal painClinical symptoms of abdominal pain

CT scan – dilated pancreatic duct CT scan – dilated pancreatic duct and multiple splenic nodulesand multiple splenic nodules

CT guided biopsy of spleenCT guided biopsy of spleen

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Differential diagnosisDifferential diagnosis

Vascular lesions of the spleen Vascular lesions of the spleen include:include:

Hemangioma Hemangioma

AngiosarcomaAngiosarcoma

Splenic hamartoma Splenic hamartoma

Littoral cell angiomaLittoral cell angioma

HemangioendotheliomaHemangioendothelioma

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IHCIHCFactor VIII Kp-1

CD34 LCA

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Littoral Cell AngiomaLittoral Cell Angioma Rare, primary benign Rare, primary benign

vascular neoplasmvascular neoplasm Arising from the Arising from the

normal littoral cells normal littoral cells lining the sinusoids of lining the sinusoids of splenic red pulp.splenic red pulp.

Etiology is unclearEtiology is unclear No predilection for No predilection for

gender or age gender or age 2 forms: 2 forms:

multiple nodulesmultiple nodules solitary lesionsolitary lesion

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Littoral Cell AngiomaLittoral Cell AngiomaHistologic FeaturesHistologic Features

Anastomosing, closely Anastomosing, closely packed congested packed congested sinusoidal vascular sinusoidal vascular channels with focal channels with focal papillary fronds & papillary fronds & cystic spacescystic spaces

Endothelial lining cells Endothelial lining cells have no evidence of have no evidence of mitotic activity or mitotic activity or nuclear atypianuclear atypia

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LCALCA Fine needle aspiration biopsies (FNAB) -Fine needle aspiration biopsies (FNAB) -

infrequently performed on spleeninfrequently performed on spleen FNAB mostly used for: Sarcoid, FNAB mostly used for: Sarcoid,

Amyloidosis, infectious diseases, & Amyloidosis, infectious diseases, & lymphomaslymphomas The purpose of the FNA in this patient was to The purpose of the FNA in this patient was to

rule out sarcoidrule out sarcoid Cell block is essential in this case in order Cell block is essential in this case in order

to do IHCto do IHC Tumor cells are positive for Factor VIII and Tumor cells are positive for Factor VIII and

Kp-1 (CD68), but negative for CD34 and Kp-1 (CD68), but negative for CD34 and MIB-1MIB-1

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Cytologic Appearance of Cytologic Appearance of GranulomaGranuloma

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Case 3Case 3

Bellevue opened for clinical instruction to medical students in 1847, and opened the Bellevue Hospital Medical College in 1860

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Patient HistoryPatient History

79 year old female79 year old female Co-morbidities: diabetes, Co-morbidities: diabetes,

hypertension, hypothyroidismhypertension, hypothyroidism Right thyroid noduleRight thyroid nodule

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Nuclear changes in PTC

Fischer AH, et al. Papillary thyroid carcinoma oncogene (RET/PTC) alters the nuclear envelope and chromatin structure. Am J Pathology 1998; 153:1443-50.

Viral injection of RET/PTC oncogene to follicular cells in tissue culture

Disorganization of nuclear lamins A, B, C Nuclei of cultured cells changed from

follicular to papillary.

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PTC Normal follicular cells

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Follow upFollow up

Patient had a total thyroidectomy Patient had a total thyroidectomy one month later…one month later…

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Right thyroid lobe – 5.5cm circumscribed nodule

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Inclusions

Nuclear clearing

Grooves

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Final DiagnosisFinal Diagnosis

Papillary thyroid carcinoma (PTC)Papillary thyroid carcinoma (PTC)

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PTCPTC

Most frequent primary malignancy Most frequent primary malignancy of the thyroid (60%)of the thyroid (60%)

Most are slow growing neoplasmsMost are slow growing neoplasms Metastasize via lymphatics to Metastasize via lymphatics to

regional lymph nodesregional lymph nodes

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Cytologic Diagnosis of PTCCytologic Diagnosis of PTC

Smears are usually cellularSmears are usually cellular Papillary fronds with columnar and Papillary fronds with columnar and

cuboidal epithelium predominatecuboidal epithelium predominate Can undergo cystic change, which Can undergo cystic change, which

can cause one to mistake it for a can cause one to mistake it for a cystic goiter (9% of cases in one cystic goiter (9% of cases in one study)study)

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Papillary fronds Chewing gum colloid

Nuclear grooves/clearing Inclusions

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PTC – other cytologic PTC – other cytologic featuresfeatures

Psammoma bodiesPsammoma bodies MNGsMNGs Oncocytic (Hurthle cell) changeOncocytic (Hurthle cell) change

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PTCPTC

Diagnosis of PTC cannot be Diagnosis of PTC cannot be established on the basis of any established on the basis of any single feature, but on several single feature, but on several features in the appropriate clinical features in the appropriate clinical setting.setting.

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Case 4Case 4

The nation’s first outpatient department, called the Bureau of Medical and Surgical Relief for the Outdoor Poor opened at Bellevue in the 1800’s.This is the intern staff at Bellevue Hospital in 1877. William Halstead is in the center.

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Patient HistoryPatient History

25 year old male25 year old male Presented at FNA clinicPresented at FNA clinic Vague swelling/firmness, Vague swelling/firmness,

submandibular areasubmandibular area Aspiration biopsy was performedAspiration biopsy was performed

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Cytologic InterpretationCytologic Interpretation

Atypical oncocytic neoplasmAtypical oncocytic neoplasm Cells have prominent nucleoli, Cells have prominent nucleoli,

dense cytoplasm and high n/c dense cytoplasm and high n/c ratiosratios

Histologic evaluation was Histologic evaluation was recommendedrecommended

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Follow upFollow up

The patient had an excision of the The patient had an excision of the mass two months later…mass two months later…

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Left submandibular gland – 1.4cm tumor

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Mucin stain

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Final tissue diagnosisFinal tissue diagnosis

Mucoepidermoid carcinoma, high Mucoepidermoid carcinoma, high gradegrade

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Mucoepidermoid Mucoepidermoid CarcinomaCarcinoma

MEC accounts for 34% of salivary MEC accounts for 34% of salivary gland malignancies, and 16% of all gland malignancies, and 16% of all salivary gland neoplasmssalivary gland neoplasms

Most common malignant salivary Most common malignant salivary gland neoplasm in persons <20 gland neoplasm in persons <20 yearsyears

50% in major salivary glands50% in major salivary glands

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Mucoepidermoid Mucoepidermoid CarcinomaCarcinoma

Three cell types make up this Three cell types make up this tumor:tumor: Mucin producing cellsMucin producing cells Intermediate cellsIntermediate cells Epidermoid cellsEpidermoid cells

Identification of all three cell types Identification of all three cell types is necessary to make this diagnosisis necessary to make this diagnosis

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Mucoepidermoid Mucoepidermoid CarcinomaCarcinoma

MEC is classified as low grade or MEC is classified as low grade or high gradehigh grade

Low grade MEC has a prominence Low grade MEC has a prominence of mucin producing cells, while of mucin producing cells, while high grade MEC shows more high grade MEC shows more epidermoid cells, and less mucinepidermoid cells, and less mucin

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Differential DiagnosisDifferential Diagnosis

Low grade MEC:Low grade MEC: Warthin’s tumorWarthin’s tumor Chronic Chronic

sialadenitissialadenitis Pleomorphic Pleomorphic

adenomaadenoma

High Grade MEC:High Grade MEC: SCC (metastatic or SCC (metastatic or

primary)primary) Acinic cell Acinic cell

carcinomacarcinoma Clear cell Clear cell

neoplasmsneoplasms EtOH fixationEtOH fixation

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Bonus CaseBonus Case

The “Belle Vue” mansion was used as a pesthouse during the yellow fever epidemic of 1794, and the name was later given to the hospital that took its place

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Patient HistoryPatient History

Clinical historyClinical history 28 year old transvestite sex worker 28 year old transvestite sex worker

from Ecuadorfrom Ecuador HIV+HIV+ Enlarged right cervical lymph nodeEnlarged right cervical lymph node Aspiration biopsy was performedAspiration biopsy was performed

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Follow upFollow up

The patient had a biopsy of a The patient had a biopsy of a cavitary lung lesion a few days cavitary lung lesion a few days later…later…

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Blastomycosis dermatiditisBlastomycosis dermatiditis

8-15 μm8-15 μm Granulomatous fungal infection.Granulomatous fungal infection. In 1894, Gilchrist first described it in the In 1894, Gilchrist first described it in the

United States. United States. Endemic in North America (eg, near the Endemic in North America (eg, near the

Mississippi River, Ohio River, Great Mississippi River, Ohio River, Great Lakes). Lakes).

Infection occurs by inhalation of the Infection occurs by inhalation of the fungus from its natural soil habitat.fungus from its natural soil habitat.

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Blastomycosis dermatiditisBlastomycosis dermatiditis Conidia transform at body Conidia transform at body

temperature to the yeast temperature to the yeast phase (thermal dimorphism). phase (thermal dimorphism).

Microforms (2-4 μm); Microforms (2-4 μm); intracellular yeast which intracellular yeast which resemble resemble Histoplasma Histoplasma capsulatum or Cryptococcus capsulatum or Cryptococcus neoformansneoformans

Pleomorphic yeast-like cells Pleomorphic yeast-like cells (2-20 μm) and formation of (2-20 μm) and formation of narrow-based buds. narrow-based buds.

The encapsulated strains The encapsulated strains have capsular material have capsular material detected with mucin stain detected with mucin stain giving the appearance of a giving the appearance of a clear zone around a faint clear zone around a faint round nucleus.round nucleus.

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Thank you!Thank you!