Lung Tumor Cases: Common Problems and Helpful Hints Brandon T. Larsen, MD, PhD Senior Associate Consultant Department of Laboratory Medicine and Pathology Mayo Clinic Arizona Arizona Society of Pathologists Spring 2018 Meeting April 7, 2018 2013 MFMER slide-1 Disclosures Relevant financial relationships: None Off-label usage: None 2013 MFMER slide-2 1
Case 1 69 y.o. F with an enlarging 1.4-cm partially ground-glass, partially solid nodule in RUL Core bxs obtained 2013 MFMER slide-3 2013 MFMER slide-4 2
2013 MFMER slide-5 2013 MFMER slide-6 3
2013 MFMER slide-7 2013 MFMER slide-8 4
2013 MFMER slide-9 2013 MFMER slide-10 5
2013 MFMER slide-11 2013 MFMER slide-12 6
ARS Polling Question How would you classify this lesion? 1. Peribronchiolar metaplasia / reactive 2. AAH 3. AIS 4. MIA 5. Adenocarcinoma, with at least focal invasion 2013 MFMER slide-13 2013 MFMER slide-14 7
2013 MFMER slide-15 Case #1: My Diagnosis Adenocarcinoma, with at least focal invasion 2013 MFMER slide-16 8
Common Problem #1 PB metaplasia, AAH, AIS, MIA, or invasive adenocarcinoma? Helpful Hints Have a low threshold for calling invasive if stromal reaction or alveolar wall expansion is present AIS is extremely rare Know the CT findings AIS 2013 MFMER slide-17 Case 2 73 y.o. M with history of bx-proven small cell carcinoma in LUL 6 months ago Now with large consolidative opacity in RML/RLL 2013 MFMER slide-18 9
2013 MFMER slide-19 2013 MFMER slide-20 10
2013 MFMER slide-21 2013 MFMER slide-22 11
2013 MFMER slide-23 2013 MFMER slide-24 12
2013 MFMER slide-25 2013 MFMER slide-26 13
2013 MFMER slide-27 ARS Polling Question How would you classify this lesion? 1. Malignant 2. Suspicious 3. Atypical 4. Benign 5. Unsure I need stains 2013 MFMER slide-28 14
Additional Clinical History Recent etoposide and radiation therapy Clinical suspicion: Must be an adverse reaction to etoposide and/or radiation 2013 MFMER slide-29 2013 MFMER slide-30 15
2013 MFMER slide-31 Case #2: My Diagnosis Organizing acute lung injury with striking reactive atypia and vacuolization of pneumocytes, consistent with reaction to drug (? etoposide) and/or radiation 2013 MFMER slide-32 16
Common Problem #2 Reactive or cancer? Helpful Hints If acute lung injury is present, think twice before diagnosing cancer DAD, AFOP, OP Know the clinical history 2013 MFMER slide-33 Case 3 64 y.o. M with diffuse bilateral pulmonary nodules Clinical impression: Granulomatous disease vs. metastases Transbronchial bxs obtained 2013 MFMER slide-34 17
2013 MFMER slide-35 2013 MFMER slide-36 18
2013 MFMER slide-37 2013 MFMER slide-38 19
2013 MFMER slide-39 ARS Polling Question How would you classify this tumor? 1. Goblet cell metaplasia 2. Atypical but insufficient for dx recommend re-biopsy 3. AIS, mucinous type 4. Invasive mucinous adenocarcinoma 5. I have no idea 2013 MFMER slide-40 20
2013 MFMER slide-41 2013 MFMER slide-42 21
Case #3: My Diagnosis Invasive mucinous adenocarcinoma 2013 MFMER slide-43 Common Problem #3 Bland mucinous lesion Helpful Hints Remember, mucinous adenoca is: Deceptively bland Deceptively lepidic, but high-grade, aggressive, and virtually always invasive Deceptively enteric 2013 MFMER slide-44 22
CDX2 2013 MFMER slide-45 Case 4 91 y.o. M with bulky lung mass, pleural effusion, hilar lymphadenopathy, and possible metastasis to adrenal gland Pleural bxs obtained 2013 MFMER slide-46 23
2013 MFMER slide-47 2013 MFMER slide-48 24
2013 MFMER slide-49 Positive Vimentin Pankeratin CAM5.2 CD68 IHC Results Negative S100 HMB45 Melan-A CK5/6 MOC31 CEA BerEP4 CD15 B72.3 desmin CD3 CD20 CD45 CD79a MUM1 CD34 Bcl-2 Calretinin D2-40 SMA 2013 MFMER slide-50 25
ARS Polling Question How would you classify this tumor? 1. Sarcomatoid carcinoma 2. Undifferentiated pleomorphic sarcoma 3. Sarcomatoid melanoma 4. Sarcomatoid malignancy, NOS 5. I want more stains 2013 MFMER slide-51 TTF-1 2013 MFMER slide-52 26
Case #4: My Diagnosis Sarcomatoid carcinoma, most likely of pulmonary origin with pleural metastasis 2013 MFMER slide-53 Common Problem #4 Spindle cell lesion in lung Helpful Hints For pleomorphic spindle cell tumors in the lung, sarcomatoid carcinoma is most likely Don t forget lymphoma and metastasis (melanoma, GYN, etc.) 2013 MFMER slide-54 27
Case 5 68 y.o. M with a 20-pack-year smoking hx, with a 3.5 cm round, well-circumscribed, pleuralbased mass Core bx obtained 2013 MFMER slide-55 2013 MFMER slide-56 28
2013 MFMER slide-57 2013 MFMER slide-58 29
2013 MFMER slide-59 2013 MFMER slide-60 30
ARS Polling Question What is the most likely diagnosis? 1. Solitary fibrous tumor 2. Malignant solitary fibrous tumor 3. Sarcomatoid mesothelioma 4. Sarcomatoid carcinoma 5. Something else / not sure 2013 MFMER slide-61 2013 MFMER slide-62 31
2013 MFMER slide-63 S100 2013 MFMER slide-64 32
CD34 2013 MFMER slide-65 Case #5: My Diagnosis Schwannoma, with degenerative changes 2013 MFMER slide-66 33
Common Problem #5 Spindle cell lesion in pleura Helpful Hints Think twice about malignancy when a pleomorphic spindle cell tumor lacks mitoses and necrosis Don t forget the chest wall with pleural lesions Know the clinical hx and imaging findings 2013 MFMER slide-67 Case 6 39 y.o. F in motor vehicle accident Incidentally discovered 1.6 cm round, wellcircumscribed nodule in LUL, faintly FDG-avid Wedge resection performed 2013 MFMER slide-68 34
2013 MFMER slide-69 2013 MFMER slide-70 35
2013 MFMER slide-71 2013 MFMER slide-72 36
2013 MFMER slide-73 2013 MFMER slide-74 37
2013 MFMER slide-75 2013 MFMER slide-76 38
2013 MFMER slide-77 ARS Polling Question What is the most likely diagnosis? 1. Pulmonary hamartoma 2. Myoepithelioma 3. Primary pulmonary myxoid sarcoma 4. Extraskeletal myxoid chondrosarcoma 5. I have no idea 2013 MFMER slide-78 39
SMA 2013 MFMER slide-79 IHC Results Positive SMA (weak, focal) Negative AE1/AE3 Desmin Cd34 S100 TTF-1 FISH Testing Positive for EWSR1 rearrangement Negative for NR4A3 rearrangement 2013 MFMER slide-80 40
FISH Interpretation Caution! Tumors with EWSR1 gene rearrangement Ewing sarcoma / PNET Clear cell sarcoma of soft tissue Clear cell sarcoma-like tumor of GI tract Desmoplastic small round cell tumor Angiomatoid fibrous histiocytoma Myoepithelial tumors Extraskeletal myxoid chondrosarcoma Primary pulmonary myxoid sarcoma Hyalinizing clear cell carcinoma of salivary / bronchial glands Mesothelioma Hemangioma of bone Low-grade fibromyxoid sarcoma / Sclerosing epithelioid fibrosarcoma Myxoid liposarcoma Osteosarcoma, small cell variant Clear cell odontogenic carcinoma 2013 MFMER slide-81 FISH Interpretation Caution! Tumors with EWSR1-CREB1 translocation Primary pulmonary myxoid sarcoma Angiomatoid fibrous histiocytoma Hyalinizing clear cell carcinoma of bronchial submucosal glands Clear cell sarcoma of soft tissue Clear cell sarcoma-like tumor of the GI tract Hyalinizing clear cell carcinoma of salivary gland 2013 MFMER slide-82 41
Case #6: My Diagnosis Primary pulmonary myxoid sarcoma 2013 MFMER slide-83 Common Problem #6 Bland myxoid lesion Helpful Hints FISH is essential, but insufficient; combination of IHC and FISH needed EWSR1 rearrangements and even EWSR1-CREB1 translocations seen in many tumor types 2013 MFMER slide-84 42
Case 7 48 y.o. M with extensive smoking history, 7 cm mass in the right lung Core bxs obtained 2013 MFMER slide-85 2013 MFMER slide-86 43
2013 MFMER slide-87 2013 MFMER slide-88 44
2013 MFMER slide-89 AE1/AE3 2013 MFMER slide-90 45
TTF-1 2013 MFMER slide-91 p40 2013 MFMER slide-92 46
CD34 2013 MFMER slide-93 CD45 2013 MFMER slide-94 47
ARS Polling Question How would you classify this tumor? 1. AdenoCa, poorly diff. 2. Squamous cell Ca, poorly diff. 3. High-grade lymphoma 4. High-grade angiosarcoma 5. I give up maybe I should retire early 2013 MFMER slide-95 NUT 2013 MFMER slide-96 48
NUT 2013 MFMER slide-97 Case #7: My Diagnosis NUT carcinoma 2013 MFMER slide-98 49
Common Problem #7 The immunos don t make sense Helpful Hints Repeat markers, maybe in another lab Vascular, melanoma, lymphoma markers Remember tumors with weird IHC patterns: NUT carcinoma SMARCA4-deficient thoracic sarcoma 2013 MFMER slide-99 50