ILLINOIS
REGISTRY OF
ANATOMIC PATHOLOGY
CASE HISTORIES AND DIAGNOSES
FEBRUARY 23, 2015
Case #1
PRESENTER: Elisheva Shanes, MD
ATTENDING: Lin Liu, MD
CASE HISTORY: A 66-year-old female never-smoker was incidentally found to have a calcified nodule in
the left lower lobe of her lung. Repeat imaging demonstrated interval enlargement, and she underwent a
wedge resection with completion segmentectomy.
DIAGNOSIS:
- Typical carcinoid tumor
- Multiple neuroendocrine tumorlets
- Pulmonary neuroendocrine cell hyperplasia
DISCUSSION:
- Pulmonary neuroendocrine cell hyperplasia is commonly associated with chronic hypoxic and/or
inflammatory conditions of the lung.
- Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a distinct entity
described and named in 1992 by Aguayo et. al.
o Classically associated with cough, dyspnea, evidence of airway obstruction.
o Almost all case reports are in females, generally middle-aged.
o Not related to pre-existing lung disease – an absence of background disease is
necessary for diagnosis.
o Characterized by a mosaic attenuation pattern and multiple pulmonary nodules on high
resolution CT of the chest.
o Its association with carcinoid tumors has led to its classification by the WHO as a preneoplastic condition.
- The WHO definition of DIPNECH:
o “a generalized proliferation of scattered single cells, small nodules (neuroendocrine
bodies), or linear proliferations of pulmonary neuroendocrine cells (PNCs) that may be
confined to the bronchial and bronchiolar epithelium, include local extraluminal
proliferation in the form of tumorlets, or extend to the development of carcinoid tumors”
o “sometimes accompanied by intra- and extralumnial fibrosis of involved airways, but other
pathology that might induce reactive PNC proliferation is absent”
- There are currently no objective criteria for the diagnosis of DIPNECH.
o Currently generally reserved for symptomatic patients or patients with characteristic
imaging.
o PNECH is commonly found in asymptomatic patients undergoing resection for carcinoid
tumors.
 Many patients do not have high resolution CT scans.
o February 2015 Human Pathology, Marchevsky et. al. propose objective criteria:
 5 or more NE cells, singly or in clusters located within the basement membrane
of the bronchiolar epithelium of at least 3 bronchioles,
PLUS
 3 or more carcinoid tumorlets
- Characterization of PNECH with regards to the transition from hyperplasic proliferation to
neoplastic is ongoing.
REFERENCES:
1. Chassagnon G, Favelle O, Marchand-Adam S, et. al. DIPNECH: when to suggest this diagnosis on
CT. Clin Radiol 2015 Mar; 70(3):317-25.
2. Davies S, Gosney JR, Hansell DM, et. al. Diffuse idiopathic pulmonary neuroendocrine cell
hyperplasia: an under-recognised spectrum of disease. Thorax 2007 Mar; 62(3):248-52.
3. den Bakker MA and Thunnissen FBJM. Neuroendocrine tumours – challenges in the diagnosis and
classification of pulmonary neuroendocrine tumours. J Clin Pathol 2013 Oct; 66(10):862-9.
4. Finkelstein SD, Hasegawa T, Colby T, Yousem SA. 11q13 allelic imbalance discriminates pulmonary
carcinoids from tumorlets. Am J Pathol 1999 Aug ;155(2):633-40.
5. Gossney JR, Williams IJ, Dodson AR, Foster CS. Morphology and antigen expression profile of
pulmonary neuroendocrine cells in reactive proliferations and diffuse idiopathic pulmonary
neuroendocrine cell hyperplasia (DIPNECH). Histopathology 2011 Oct; 59(4):751-62.
6. Marchevsky A, Wirtschafter E, Walts A. The spectrum of changes in adults with multifocal pulmonary
neuroendocrine proliferations: what is the minimum set of pathologic criteria to diagnose DIPNECH?
Hum Path 2015 Feb; 46(2):176-81.
7. Miller R and Muller N. Neuroendocrine cell hyperplasia and obliterative bronchiolitis in patients with
peripheral carcinoid tumors. Am J Surg Path 1995 Jun; 19(6):653-8.
8. Rizvi SMH, Goodwill J, Lim E, et. al. The frequency of neuroendocrine cell hyperplasia in patients
with pulmonary neuroendocrine tumours and non-neuroendocrine cell carcinomas. Histopathology
2009 Sep; 55(3):332-7.
Case #2:
PRESENTER: Michael Eckhardt, MD
ATTENDING: James Padgett, MD
CASE HISTORY: The patient is a 60 year old female who presented with epigastric pain worsened by
bowel movement and worsening diarrhea. She has a history of anal cancer in 2006, s/p chemoradiation
with chronic diarrhea, but this is worse than usual. She underwent an EGD and colonoscopy which were
both negative, and a CT showed a lesion in the pancreatic body. She then underwent a distal
pancreatectomy/splenectomy.
DIAGNOSIS: Hepatoid carcinoma of the pancreas
IMPORTANT DIFFERENTIAL DIAGNOSES:
 Pancreatic adenocarcinoma
 Acinar cell carcinoma
 Pancreatic neuroendocrine tumor
 Solid pseudopapillary neoplasm
 Metastatic hepatocellular carcinoma
DISCUSSION:
 Rare neoplasm with histological features and immunophenotype of hepatocellular carcinoma
without evidence of a primary liver lesion
o Most commonly seen in stomach, but can occur anywhere
o 22 cases described in the pancreas
 Etiology of tumor is unknown
o Theories include hepatocellular carcinoma within ectopic liver, pancreas to liver
“transdifferentiation”, and embryological precursor cells
 Histology:
o Medium to large polygonal cells, eosinophillic cytoplasm with vesicular nuclei and
prominent nucleoli in perisinusoidal pattern with bile, and IHC of HCC
o Can be pure or mixed with other components
 Neuroendocrine tumor
 Ductal adenocarcinoma
 Encapsulated adenoma
o Pure form has better survival than mixed form
 1/10 vs. 6/11 have died of pure form vs. mixed form to date
 Treatment:
o Best disease free survival is radical surgical resection
o Adjuvant therapy post surgery unclear
 Disease-free survival increased with adjuvant chemotherapy
 Key points:
o Hepatoid carcinoma of pancreas RARE
o Can share microscopic features with other common pancreatic tumors
o Pure form more indolent than mixed form
o Need to rule out metastatic HCC
o No standardized treatment
 Surgical resection yields best results
 Chemo and radiation may be helpful for recurrent disease
REFERENCES:
1. Dabbs D, et al. Diagnostic Immunohistochemistry. Philidelphia: Saunders Elsevier, 2010.
2. Marchegiani G, et al. Pancreatic hepatoid carcinoma: A review of the literature. Dig Surg 2013; 30(46):425-33.
3. Majumder S, and Dasanu C. Hepatoid variant of pancreatic cancer: Insights from a case and
literature review. J Pancreas 2013 Jul 10; 14(4):442-5.
4. Steen S, et al. Primary hepatocellular carcinoma ("hepatoid" carcinoma) of the pancreas: A case
report and review of the literature. Clin Case Rep 2013 Dec; 1(2):66-71.
5. Su JS, et al. Clinicopathological characteristics in the differential diagnosis of hepatoid
adenocarcinoma: A literature review. World J Gastroenterol 2013 Jan 21; 19(3):321-7.
6. Jung JY, et al. Hepatoid carcinoma of the pancreas combined with neuroendocrine carcinoma. Gut
Liver 2010 Mar; 4(1):98-102.
Case #3
PRESENTER: Garrison Pease, MD
ATTENDING: William Watkin, MD
CASE HISTORY: A 66 year old female Caucasian, non-smoker and homemaker, presented with 6
months of progressive exertional dyspnea  2 months dyspnea at rest with fits of intractable coughing.
 Unresolved by bronchodilators and two cycles of azithromycin, prednisone with marginal relief.
 Imaging (CT) demonstrated bilateral diffuse extensive ground glass opacities and no adenopathy.
 Multiple wedge biopsies were performed.
HISTOPATHOLOGY: Bronchiolocentric granulomatous inflammation. Granulomas are tight, isolated,
rarely necrotizing, and have a cuff of chronic inflammatory cells. Uninvolved lung parenchyma is
unremarkable.
 GMS negative, AFB and fungal cultures negative at 4 weeks and 8 weeks.
 Differential diagnoses: sarcoidosis, hypersensitivity pneumonitis, berylliosis, granulomatous
infection.
 AFB staining revealed rare acid fast bacteria. Patient also has history of residential hot tub use.
DIAGNOSIS: Granulomatous interstitial pneumonia with focal necrosis and rare acid fast organisms,
most consistent with inhalational reaction to atypical mycobacteria, or “hot tub lung.”
DISCUSSION: Hot tub lung was first described in 1997 by Kahana et al, a case of 2-6 months of
dyspnea, cough, hypoxia, and fever in a non-smoking patient with no history of chronic lung disease.
Currently, hot tub lung is considered its own diagnostic entity with characteristic clinical presentation and
histopathology.
 Clinical history consists of regular use of an indoor/residential hot tub that is not cleaned at
recommended intervals, in a poorly ventilated room.
 CT demonstrates a diffuse ground-glass pattern infiltrate.
 Histopathology shows tight non-necrotizing granulomas with a cuff of inflammatory cells in a
bronchiolocentric and interstitial pattern.
 AFB stains are uncommonly positive, while AFB cultures of the lung tissue, water, or hot tub
structures are often positive.
 Case series report resolution of symptoms via abstinence from hot tub use, antimycobacterials,
corticosteroids, and combinations of these approaches.
 Most favor that hot tub lung is a hypersensitive-type reaction to the atypical mycobacteria. This is
supported by the initiation and resolution based on hot tub exposure and cessation, resolution of
symptoms from steroid use, radiography similar to that of hypersensitivity pneumonitis, and nonnecrotizing granulomas.
DIFFERENTIATING FACTORS FOR GRANULOMATOUS INFLAMMATION OF THE LUNG:
Entity
Granuloma
Granuloma distribution
Other findings
Our patient, “Hot tub
lung”
Tight, isolated,
prominent
Peribronchiolar,
airspaces
Indoor residential hot
tub exposure
Hypersensitivity
pneumonitis
Small, loose &
inconspicuous
Interstitial; inflammation
overshadows the
granulomas
BOOP, antigen
exposure history (i.e.
humidifier lung,
Farmer’s lung)
Entity
Granuloma
Granuloma distribution
Other findings
Berylliosis
Tight, MNGCs with
Schaumann and
asteroid bodies
Peribronchiolar,
airspaces
Exposure history (i.e.
aerospace industry),
chronic interstitial
inflammation
Sarcoidosis
Tight, coalescing with
hyalinization, nonnecrotizing, few lymphs
Perilymphatic, pleural,
septal, peribronchial,
perivascular
Pneumonia usually NOT
observed; adenopathy,
multiple organ
involvement
Granulomatous
infection
Necrotizing and nonnecrotizing
Bronchiolocentric
Slow cure by
antimycobacterials
SELECTED REFERENCES, ANNOTATED:
1. Kahana LM, Kay JM, Yakrus MA, Waserman S. Mycobacterium avium complex infection in an
immunocompetent young adult related to hot tub exposure. Chest 1997 Jan; 111(1):242-5.
 This is the first case report published, differentiating it from sarcoidosis.
2. Hanak V, Kalra S, Aksamit TR, et al. Hot tub lung: presenting features and clinical course of 21
patients. Respir Med 2006 Apr; 100(4):610-5.
 Case series of 21 patients, clinical and radiological resolution via hot tub abstinence.
3. Khoor A, Leslie KO, Tazelaar HD, et al. Diffuse pulmonary disease caused by nontuberculous
mycobacteria in immunocompetent people (hot tub lung). Am J Clin Pathol 2001 May; 115(5):755-62.
 Case series of 10 patients, clinical and radiological resolution via corticosteroids,
antimycobacterials, or both.
4. Aksamit TR. Hot tub lung: infection, inflammation, or both? Semin Respir Infect 2003 Mar;18(4):33-9.
5. Embil J, Warren P, Yakrus M, et al. Pulmonary illness associated with exposure to Mycobacteriumavium complex in hot tub water. Hypersensitivity pneumonitis or infection? Chest 1997 Mar;
111(3):813-6.
 These both discuss pathophysiology of hot tub lung.
6. Leslie KO, Wick MR, (eds). Practical Pulmonary Pathology: A Diagnostic Approach. Second edition.
Elsevier Saunders: Philadelphia, 2011.
 Textbook provides clinical, radiological, and histopathologic information (including images) on
differential diagnoses discussed: Sarcoidosis, Hypersensitivity pneumonitis, Berylliosis,
Granulomatous infection, and Hot tub lung.
ADDITIONAL REFERENCES:
7. Rickman OB, Ryu JH, Fidler ME, Kalra S. Hypersensitivity pneumonitis associated with
Mycobacterium avium complex and hot tub use. Mayo Clin Proc 2002 Nov; 77(11):1233-7.
8. Mangione EJ, Huitt G, Lenaway D, et al. Nontuberculous mycobacterial disease following hot tub
exposure. Emerg Infect Dis 2001 Nov-Dec; 7(6):1039-42.
9. Katzenstein A-LA. Surgical Pathology of Non-neoplastic Lung Disease. Fourth ed. Elsevier
Saunders: Philadelphia, 2006.
Case #4
PRESENTER: Saman S. Ahmadian, MD
ATTENDING: John M. Lee, MD PhD
CASE HISTORY: 23 y/o female came to the clinic with a history of headaches for 10 years which were
changing in frequency and in pattern since 3 months before admission. Physical examination including
neurologic examination was normal.
DIAGNOSIS: Pleomorphic xanthoastrocytoma (PXA; WHO Grade II)
IMPORTANT DIFFERENTIAL DIAGNOSES:
 Ganglioglioma
 Infiltrative astrocytoma
KEY DIAGNOSTIC FEATURES:
 Rare cause of astrocytic neoplasm (1%) which presents in an atypical pattern similar to
infiltrative astrocytoma
o Infiltrative pattern
o Mild pleomorphism
o No xanthomatous changes
o No eosinophilic granular bodies
 Special studies include:
o GFAP, S100, synaptophysin, reticulin
o BRAF V600E, MGMT promoter methylation
SUMMARY: PXA and infiltrative astrocytoma can present with similar histopathological features on H&E
examination but their treatment approaches are different. While primary PXA (without features of
anaplasia) is best treated with complete removal of the tumor alone, infiltrative astrocytoma usually needs
surgery along with chemo-radio therapy. Furthermore, the presence of new targeted treatment methods
against BRAF V600E makes the differentiation of these two neoplasms important.
REFRENCES:
1. Camelo-Piragua S, Jansen M, Ganguly A, et al: A sensitive and specific diagnostic panel to
distinguish diffuse astrocytoma from astrocytosis: chromosome 7 gain with mutant isocitrate
dehydrogenase 1 and p53. J Neuropathol Exp Neurol 2011 Feb; 70(2):110-5.
2. WHO Classification of Tumours of the Central Nervous System. Louis DN, H. Ohgaki, O. D. Wiestler,
W. K. Cavenee, eds. World Health Organization, 2007.
3. Rosai, Juan. Rosai and Ackerman's Surgical Pathology. Mosby, 2011.
4. Kepes JJ, Rubinstein LJ, Eng LF: Pleomorphic xanthoastrocytoma: a distinctive meningocerebral
glioma of young subjects with relatively favorable prognosis. A study of 12 cases. Cancer 1979 Nov;
44(5):1839-52.
5. Giannini C, Scheithauer BW, Lopes MB, et al. Immunophenotype of pleomorphic xanthoastrocytoma.
Am J Surg Pathol 2002 Apr; 26(4):479-85.
6. Neuropathology: A Reference Text of CNS Pathology, Edition 3. Ellison D, ed. Mosby, 2013.
7. Horbinski C. To BRAF or not to BRAF: Is that even a question anymore? J Neuropathol Exp Neurol
2013 Jan; 72(1):2-7.
8. Pahapill PA, Ramsay DA, Del Maestro RF. Pleomorphic xanthoastrocytoma: case report and analysis
of the literature concerning the efficacy of resection and the significance of necrosis. Neurosurgery
1996 Apr; 38(4):822–8.
9. Koga T, Morita A, Maruyama K, et al. Long-term control of disseminated pleomorphic
xanthoastrocytoma with anaplastic features by means of stereotactic irradiation. Neuro Oncol 2009
Aug;11:446–51.
10. Giannini C, Scheithauer BW, Burger PC, et al. Pleomorphic xanthoastrocytoma: what do we really
know about it? Cancer 1999 May 1; 85(9):2033–45.
11. Chang HT, Latorre JG, Hahn S, et al. Pediatric cerebellar pleomorphic xanthoastrocytoma with
anaplastic features: a case of long-term survival after multimodality therapy. Childs Nerv Syst 2006
Jun; 22:609–13.
12. Lindboe CF and Hansen HB: Epiperikaryal synaptophysin reactivity in the normal human central
nervous system. Clin Neuropathol 1998 Sep-Oct; 17(5):237-40.
13. Gianni C, Scheithauer BW, Lopes MB, et al. Immunophenotype of pleomorphic xanthoastrocytoma.
Am J Surg Pathol 2002 Apr; 26(4):479-85.
14. Gururangan S, Fisher MJ, Allen JC, et al. Temozolomide in children with progressive low-grade
glioma. Neuro Oncol 2007 Apr; 9(2):161-8.
Case # 5:
PRESENTER: Myra Khan, DO
ATTENDING: Mohamed Eldibany, MD
CASE HISTORY:
The patient is an 84 year old female who presented in October 2013 with a 6 month history of abdominal
pain and constipation
 EGD revealed an infiltrative and ulcerated non-circumferential mass on the greater curvature of
the gastric body
 CT scan with contrast displayed a perforated ulcer on the gastric fundus with marked mural
thickening
HISTOLOGY:
 Gastric biopsies showed infiltrative cellular elements of intermediate to large size, oval to round
cells, dark nuclei, fine chromatin, minimal cytoplasm, and easily identified mitosis
STAINS:
 Positive: c-MYC, BCL-6, Ki67 100%, and CD10
 Negative: BCL-2, CD3, TdT, and MUM-1
DIAGNOSIS: Double Hit Lymphoma (DHIT)
DEFINITION: DHIT is a subset of B-cell lymphoma unclassifiable characterized by a MYC translocation
with either BCL2 t(14;18) or BCL6 t(3;8) that is confirmed by FISH or cytogenetics
DIFFERENTIAL DIAGNOSES:
 Burkitt Lymphoma (BL)
 Diffuse Large B-cell Lymphoma (DLBCL)
 Double Hit Lymphoma (DHIT)
KEY DIAGNOSTIC FEATURES:
 DHIT morphology:
o “BL Like”-starry sky appearance with monomorphous, slightly larger to intermediate size
cells, with irregular nuclei and prominent nucleoli
o DLBCL-NOS -predominately large cells, irregular nuclei, with prominent nucleoli
 DHIT clinical signs and symptoms:
o Age and gender: 55-65 years old, extremely rare in children and young adults
o Presents initially as advanced lymphoma or leukemia with extranodal involvement
o LDH is elevated and greater than 3 times in comparison to patients with BL or DLBCL
o Not associated with immunosuppression
o Can arise de novo or the patient may have a history of or a current lymphoma
o Clinical course is rapidly progressive and a refractory disease despite aggressive therapy
TREATMENT:
 No treatment has been established. Trials that compare patients receiving R-CHOP or R-HyperCVAD did not show any difference in survival. Median overall survival is 4.5 months to 1 year
 Features that correlate with a more favorable prognosis are: No bone marrow involvement, a
translocation that arises de novo, and MYC translocation partner is a non-IG gene
REFERENCES:
1. Aukema SM, Sibert R, Schuuring E, et al. Double-hit B-cell lymphomas. Blood 2011 Feb 24; 117(8):
2319-31.
2. Bertrand P, Bastard C, Maingonnat C, et al. Mapping of MYC breakpoints in 8q24 rearrangements
involving non-immunoglobulin partners in B-cell lymphomas. Leukemia 2007 Mar; 21(3):515-23.
3. Choi S-Y, Kim SJ, Kim WS, et al. Aggressive B cell lymphomas of the gastrointestinal tract:
clinicopathologic and genetic analysis. Virchows Arch 2011 Nov; 459(5): 495-502.
4. Johnson NA, Al-Tourah A, Brown CJ, et al. Prognostic significance of secondary cytogenetic
alterations in follicular lymphomas. Genes Chromosomes Cancer 2008 Dec; 47(12):1038-48.
5. Johnson NA, Savage KJ, Ludkovski O, et al. Lymphomas with concurrent BCL2 and MYC
translocations: the critical factors associated with survival. Blood 2009 Sept 10;114(11):2273-9.
6. Kanungo A, Medeiros LJ, Abruzzo LV, Lin P. Lymphoid neoplasms associated with concurrent
t(14:18) and 8q24/c-MYC translocation generally have a poor prognosis. Mod Pathol 2006 Jan;
19(1):25-33.
7. Le Gouill S, Talmant P, Touzeau C, et al. The clinical presentation and prognosis of diffuse large B-cell
lymphoma with t(14:18) and 8q24 c-MYC rearrangement. Haematologica 2007 Oct; 92(10):1335-42.
8. Li S, Lin P, Fayad LE, et al. B-cell lymphomas with MYC/8q24 rearrangements and
IGH@BCL2/t(14:18)(q32;q21): an aggressive disease with heterogeneous histology, germinal center
B-cell immunophenotype and poor outcome. Mod Pathol 2011Oct; 25(1):145-56.
9. Lin P, Dickerson TJ, Fayad LE, et al. Prognostic value of MYC rearrangement in cases of B-cell
lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and
Burkitt Lymphoma. Cancer 2012 Mar15; 118(6):1566-73.
10. Lu B, Zhou C, Yang W, et al. Morphological, immunophenotypic and molecular characterization of
mature aggressive B-cell lymphomas in Chinese pediatric patients. Leuk Lymphoma 2011 Dec;
52(12):2356-64.
11. Macpherson N, Lesack D, Klasa R, te al. Small noncleaved, non-Burkitt’s (Burkitt-Like) lymphoma:
cytogenetics predict outcome and reflect clinical presentation. J Clin Oncol 1999 May; 17(5):1558-67.
12. Snuderl M, Kolman OK, Chen Y-B, et al. B-cell lymphomas with concurrent IGH-BCL2 and MYC
rearrangements are aggressive neoplasms with clinical and pathological features distinct from Burkitt
lymphoma and diffuse large B-cell lymphoma. Am J Surg Pathol 2010 Mar; 34(3):327-40.
Case # 6:
PRESENTER: Sharda Thakral, MD
ATTENDING: William Watkin, MD
CASE HISTORY:
A 76 year old female presented with fatigue, decreased appetite, and weakness of insidious onset. Work
up revealed anemia, thrombocytopenia, elevated liver enzymes, an enlarged uterus, and a 4 cm liver
mass. A liver biopsy, bone marrow biopsy, and endometrial curettage were performed, all of which
demonstrated tumor.
HISTORY:
Tumor composed of sheets of epithelioid cells with clear to eosinophilic cytoplasm, centrally-placed
nucleus, nuclear pleomorphism, multinucleated tumor cells, and frequent mitotic figures.
DIFFERENTIAL DIAGNOSES:
 Clear cell carcinoma
 Leiomyosarcoma
 Choriocarcinoma
 Melanoma
 Endometrial stromal sarcoma
 Perivascular epithelioid cell neoplasm (PEComa)
IMMUNOHISTOCHEMISTRY:
 Positive stains:
o HMB 45, Caldesmon, Calponin
 Negative stains:
o AE1/AE3, ER, S100, SOX 10, Desmin, Smooth Muscle Actin, CDX 2, PAX 8, CD 10,
Inhibin, Chromogranin, Synaptophysin
DIAGNOSIS: Malignant perivascular epitheloid cell neoplasm (PEComa)
DISCUSSION:
 PEComa:
o Mesenchymal neoplasm composed of histologically and immunohistochemically
distinctive perivascular epithelioid cells (PEC). Neoplasms show myomelanocytic
differentiation by IHC.
 PEComa Family:
o These include angiomyolipoma (AML), clear cell “sugar” tumor of the lung (CCST),
lymphangioleiomyomatosis (LAM). May occur at various visceral and soft tissue sites
including the gynecologic tract.
 Histopathology:
o The architecture is nested or in sheets. Epithelioid cells demonstrate abundant clear to
granular eosinophilic cytoplasm, a centrally placed nucleus, and have a tendency
perivascular distribution. These tumors may have a variable spindled cell component.
 Gynecologic PEComas:
o May present with vaginal bleeding. Approximately 50 cases described.
 Immunohistochemistry of Gynecologic PEComa:
o Positive stains: HMB 45, MiTF, MelanA, Smooth Muscle Actin, Desmin, Caldesmon
o Negative stains: S100 (often), AE1/AE3, PAX 8
 Transcription factor E3 (TFE3) Translocation:
o The overexpression of TFE3 occurs with a translocation involving its locus at Xp11. This
has been demonstrated in alveolar soft part sarcoma, in a subset of renal cell
carcinomas, and recently demonstrated in a subset of gynecologic PEComa which also
fail to express desmin and smooth muscle actin. PEComas harboring TFE3 translocation
theoretically may not respond to conventional therapy inhibiting mammalian target of
rapamycin (mTOR). This patient’s tumor was positive by IHC for a TFE3
translocation.
REFERENCES:
1. Gennatas C, Michalaki V, Kairi PV, et al. Successful treatment with the mTOR inhibitor everolimus in
a patient with perivascular epithelioid cell tumor. World J Surg Oncol 2012 Sep 3;10:181.
2. Hornick JL and Fletcher CD. PEComa: what do we know so far? Histopathology 2006 Jan; 48(1):7582.
3. Nucci MR and BJ Quade. Uterine mesenchymal tumors. In: Crum CP, Nucci MR, Lee KR, editors.
Diagnostic Gynecologic and Obstetric Pathology. Elsevier Inc; 2011. p. 628-29.
4. Schoolmeester JK, Dao LN, Sukov WR, et al. TFE3 Translocation-associated Perivascular Epithelioid
Cell Neoplasm (PEComa) of the Gynecologic Tract: Morphology, Immunophenotype, Differential
Diagnosis. Am J Surg Pathol 2015 Mar; 39(3):394-404.
5. Schoolmeester JK, Howitt BE, Hirsch MS, et al. Perivascular epithelioid cell neoplasm (PEComa) of
the gynecologic tract: clinicopathologic and immunohistochemical characterization of 16 cases. Am J
Surg Pathol 2014 Feb; 38(2):176-88.
6. Vang R, Kempson RL. Perivascular epithelioid cell tumor ('PEComa') of the uterus: a subset of HMB45-positive epithelioid mesenchymal neoplasms with an uncertain relationship to pure smooth muscle
tumors. Am J Surg Pathol 2002 Jan; 26(1):1-13.