Case History / 01

L. Priya Kunju / GU Pathology

Clinical History:
65-year-old male, pelvic peritoneum biopsy (status post radical cystectomy at an outside institution).

Case History / 02

Andy Sciallis / Breast Pathology

Clinical History:
A 68-year-old female with a left breast mass.

Case History / 03

Henry Appelman / Gastrointestinal Pathology

Clinical History:
A 35-year-old man with ulcerative colitis for 12 years, requiring frequent change in medication to achieve symptomatic control. Also has primary sclerosing cholangitis. Surveillance colonoscopy was performed with the finding of pancolitis with marked erythema, absent vascular pattern, friability, and erosions. 40 biopsies were obtained from throughout the colon. These are typical of all the biopsies.

Case History / 04

Sara Abbott / Breast Pathology

Clinical History:
Each slide represents a breast excision (lumpectomy or mastectomy) from a different female patient status-post neoadjuvant chemotherapy.

Case History / 05

Karen Choi / Gastrointestinal Pathology

Clinical History:
45-year-old woman. Liver biopsy for "elevated liver enzymes."

Case History / 06

Carol Farver / Thoracic Pathology

Clinical History:
66-year-old female with a history of cough, wheezing and some productive sputum; chest CT scan revealed 4.5 cm left hilar mass.

Case History / 07

Richard Cantley / Cytopathology

Clinical History:
A 45-year-old man is noted to have a soft palate lesion on routine dental examination. The mass is 1.5 cm, soft, non-ulcerated, and non-tender. He has no history of malignancy, and he is a non-smoker. Fine needle aspiration was performed, and a ThinPrep slide from the aspiration material is provided for review.

Case History / 08

Kristine Konopka / Thoracic Pathology

Clinical History:
The patient is a 32-year-old woman, who presents with left-sided chest pain and is found to have a large left pneumothorax.

Case History / 09

Sarah Choi / Hematopathology

Clinical History:
A 40-year-old woman with a history of Hashimoto’s thyroiditis presents with a mesenteric mass found incidentally on imaging.

Case History / 10

Scott Bresler / Dermatopathology

Clinical History:
A 74-year-old man with a history of type 2 diabetes mellitus and colon cancer status post resection presented with a blistering rash that healed with scarring and involved the bilateral hands, arms, abdomen, bilateral thighs, and oral mucosa. Focal areas on the dorsal hands showed milia formation. Two biopsies of the left wrist were performed, one submitted for routine histopathologic evaluation, the other for direct immunofluorescence.

Case History / 11

Daniel Boyer / Hematopathology

Clinical History:
The patient is an 82-year-old man with past medical history of hypertension, obstructive sleep apnea and prostate cancer diagnosed 2 years ago. For the past month, he and his wife noticed episodes of word-finding difficulty and nonsensical speech. MRI of the brain demonstrated a 2.3-cm enhancing mass lesion in the left parietal lobe with surrounding edema. Lumbar puncture was performed, yielding clearcolorless cerebrospinal fluid with RBC count of 1 per microliter, WBC count of 4 per microliter, protein 18 mg/dL and glucose 65 mg/dL.

Case History / 12

Paul Harms / Dermatopathology

DIAGNOSIS: Adjacent, clonally distinct borderline melanocytic tumors

Clinical History:
Tumor 1: A 52-year-old woman with no history of melanoma presented to her dermatologist with a scabbed mole on her upper arm. Shave biopsy was obtained.  No residual lesion was found upon re-excision.

Tumor 2: At her 12-month follow-up visit, the dermatologist noticed another lesion in proximity to the excision scar, of uncertain duration.  Shave biopsy was obtained.

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Microscopic Description:
Tumor 1: At low magnification, the shave biopsy demonstrated a traumatized, predominantly dermal melanocytic proliferation. Lesional melanocytes demonstrated irregular crowded growth, accompanied by cytologic atypia including hyperchromasia and mild pleomorphism.  A rare dermal mitotic figure was identified. Although the base was partly transected, the lesion appeared to mature where the base was visualized. The overlying epidermis demonstrated no evidence of melanoma in situ. No aberrancy was identified by HMB45, p16, and Ki67/MART1 immunohistochemistry. The findings raised a differential diagnosis of traumatized nevus, melanocytic tumor of uncertain malignant potential, or nevoid melanoma.

Tumor 2: At low magnification, the shave biopsy demonstrated an asymmetric, inflamed predominantly dermal melanocytic proliferation extending to margins. Lesional melanocytes displayed a spitzoid morphology characterized by large spindled to epithelioid cells with abundant amphophilic cytoplasm. Marked cytologic atypia was present in the form of pleomorphism and hyperchromasia. A rare dermal mitotic figure was identified. No aberrancy was identified by HMB45, p16, and Ki67/MART1 immunohistochemistry. The findings raised a differential diagnosis of inflamed atypical Spitz nevus, atypical Spitz tumor, spitzoid melanoma, or a satellite metastasis from Tumor #1.

Molecular Analysis
Single-nucleotide polymorphism (SNP) array analysis of Tumor 1 demonstrated NRAS Q61R mutation and no chromosomal numerical abnormality. In Tumor 2, SNP array demonstrated a distinct set of molecular changes, specifically wild-type NRAS accompanied by chromosome 1q gain and 9q loss. The SNP array results did not reach a threshold for diagnosis of melanoma in either tumor. The sum of microscopic and molecular findings supported the classification of these tumors as clonally unrelated melanocytic lesions, most compatible with adjacent unrelated nevi.

Discussion
Although the majority of melanocytic lesions can be classified as benign (nevus) or malignant (melanoma), a small percentage of melanocytic lesions display indeterminate histopathologic features. Definitive diagnosis may also be challenging in the setting of traumatized or incompletely sampled melanocytic lesions. Accurate risk stratification is essential because both under- and overdiagnosis carry risk of harm, particularly in the era of adjuvant immunotherapy for melanoma.

Melanomas display chromosomal instability, resulting in the presence of multiple segmental chromosomal gains and losses in the majority of cases.  In addition, melanomas may display specific oncogene amplification events (RREB1, CCND1, MYC) or tumor suppressor losses (homozygous CDKN2A deletion) not observed in nevi. In contrast, nevi demonstrate few or no chromosomal numerical abnormalities. Molecular tests for melanoma diagnosis have hence predominantly focused on chromosomal copy aberrations, either genome-wide by array comparative genomic hybridization (aCGH)/SNP analysis, or changes specific to melanoma by fluorescence in situ hybridization (FISH). Molecular risk stratification has been further refined in atypical Spitz tumors (ASTs), which are indeterminate melanocytic proliferations sharing features of Spitz nevi and spitzoid melanoma. In ASTs, homozygous CDKN2A deletion and TERT promoter mutation have been associated with an aggressive course; gains in RREB1 or CCND1 are also associated with risk of adverse outcome.  Based on the results of molecular analysis, challenging melanocytic tumors may be classified as low/no risk (similar to nevi) or high risk (similar to melanoma). However, molecular results must always be considered in the context of clinical, microscopic, and immunohistochemical features of a lesion.

In addition to risk stratification, our case also demonstrates a second utility for molecular analysis: evaluation of tumor clonality for staging purposes. In melanoma, primary-metastasis pairs demonstrate shared chromosomal copy number changes in the majority of cases.  When present, NRAS mutation is also shared between primary and metastasis in 92% or more of cases. Likewise, BRAF mutations are also shared in the majority of cases, although the exact frequency has been debated. This evidence suggests that aCGH/SNP analysis may be useful in evaluating the likelihood that two melanocytic lesions are related.

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References

• Balázs M et al.  Chromosomal imbalances in primary and metastatic melanomas revealed by comparative genomic hybridization. Cytometry 46:222–232 (2001)
• Bastian B et al. Classifying melanocytic tumors based on DNA copy number changes. Am J Pathol. 2003 Nov;163(5):1765-70.
• Bruno et al. BRAF mutation status may be discordant between primary-mets, although technical artifact may be a factor in this phenomenon. Oncotarget. 2017 Jan 31; 8(5): 8069–8082.
• Gerami P et al. Risk assessment for atypical spitzoid melanocytic neoplasms using FISH to identify chromosomal copy number aberrations. Am J Surg Pathol. 2013 May;37(5):676-84.
• Gerami P et al. Histomorphologic assessment and interobserver diagnostic reproducibility of atypical spitzoid melanocytic neoplasms with long-term follow-up. Am J Surg Pathol. 2014 Jul;38(7):934-40.
• Grzywa TM et al. Intratumor and Intertumor Heterogeneity in Melanoma. Transl Oncol. 2017 Dec; 10(6): 956–975.
• Harms KL et al. Atypical Spitz Tumors: A Diagnostic Challenge. Arch Pathol Lab Med. 2015 Oct;139(10):1263-70.
• Harms PW et al. Loss of p16 expression and copy number changes of CDKN2A in a spectrum of spitzoid melanocytic lesions. Hum Pathol. 2016 Dec;58:152-160
• Lee S et al.  TERT Promoter Mutations Are Predictive of Aggressive Clinical Behavior in Patients with Spitzoid Melanocytic Neoplasms. Sci Rep. 2015 Jun 10;5:11200.
• Ludgate MW. The atypical Spitz tumor of uncertain biologic potential: a series of 67 patients from a single institution.  Cancer. 2009 Feb 1;115(3):631-41.
• Pedersen MI, Wang N. Chromosomal evolution in the progression and metastasis of human malignant melanoma. A multiple lesion study. Cancer Genet Cytogenet. 1989 Sep;41(2):185-201.
• Requena C et al. TERT promoter mutations are not always associated with poor prognosis in atypical spitzoid tumors. Pigment Cell Melanoma Res. 2017 Mar;30(2):265-268.
• Schuler A et al. A Case of Adjacent, Clonally Distinct Borderline Melanocytic Tumors on the Arm. Am J Dermatopathol. 2019 Jun 28.
• Turajlic S, et al. Whole genome sequencing of matched primary and metastatic acral melanomas. Genome Res. 2012;22: 196–207.

Case History / 13

Riccardo Valdez / Hematopathology

Diagnosis: Atypical Chronic Myeloid Leukemia

Clinical History:
A 78-year-old man underwent a tooth extraction and was prescribed amoxicillin after his procedure.   He presented to an emergency room three days later with abdominal pain and weakness. A CBC revealed a white blood cell count (WBC) of 17 K/uL with a normal hemoglobin level and platelet count.  His workup was otherwise unremarkable, and he was discharged home. Five days later, he was admitted to the hospital due to severe diarrhea, where he was diagnosed with Clostridium difficile colitis and started on vancomycin.  His WBC reached 60 K/uL during his nine-day hospital admission.  Given that his WBC was normal two months before developing infectious colitis, the marked leukocytosis due to absolute neutrophilia and left-shift was attributed to a leukemoid reaction.  His WBC and absolute neutrophil counts, however, remained variably elevated following recovery (WBC ranging from 10-20 K/uL) prompting referral to the hematology clinic.  The work-up was notable for the absence of splenomegaly and a negative RT-PCR test for BCR/ABL1 fusion.  The WBC continued to fluctuate over the next several months, but when the patient developed anemia, thrombocytopenia, and rare circulating blasts, the decision was made to perform a bone marrow biopsy.

—

Microscopic Description and Ancillary Testing
The CBC at the time of the biopsy showed the following:  WBC 88.3 K/uL, HGB 11.9 g/dL, MCV 94.1 fl, and PLT 81 K/uL.  The leukocytosis was due to absolute neutrophilia; the absolute monocyte and basophil counts were in the normal range. 

The peripheral blood smear revealed a granulocytic left-shift with 2% circulating blasts and occasional nucleated red blood cells. Blasts with Auer rods were not found. Dysgranulopoiesis and thrombocytopenia with few hypogranular platelets were present.

The bone core biopsy was nearly 100% cellular due to a prominent myeloid expansion.  The aspirate smears confirmed an increased myeloid to erythroid ratio and showed a myeloid left-shift without an increase in blasts.  Dysmorphic changes were found in all three cell lines, including dyserythropoiesis with few ringed sideroblasts, and notably, prominent dysgranulopoiesis.  Conventional cytogenetics revealed the following karyotype: 46,XY,del(20)(q11.2q13.3)[15]/46,XY[5]. Interphase fluorescence in-situ hydridization (FISH) showed no abnormalities of BCR/ABL1, PDGFRA/FIP1L1, PDGFRB, or FGFR1. Molecular testing was negative for mutations in JAK2 V617F, JAK2 exon 12, MPL, and CALR.  Next-generation sequencing revealed a gain-of-function mutation in SRSF2 and loss-of-function mutation in ASXL1.

Discussion
Atypical chronic myeloid leukemia (aCML) is a neoplasm with overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). The MDS/MPN syndromes may present with clinical and morphologic features of both MDS (peripheral cytopenia and/or dysplastic bone marrow) and clonal proliferation (leukocytosis, thrombocytosis or organomegaly) as seen in MPNs. The overlap syndromes were initially recognized as a unique entity in the third edition of WHO classification of myeloid neoplasms. This group initially consisted of three disorders:  chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), and juvenile myelomonocytic leukemia. The fourth entity, MDS/MPN with ringed sideroblasts and thrombocytosis (MDS/MPN-RS-T, previously known as RARS-T), was added in the 2016 revision of WHO classification. The MDS/MPN category currently also includes a fifth group, MDS/MPN unclassifiable, which is inclusive of all other MDS/MPN -like syndromes that do not meet diagnostic criteria for the other included entities.

There is a paucity of epidemiological data on aCML. The incidence is estimated to be approximately 1–2% of BCR-ABL1-positive CML, with a median survival of 15 months (range 12.4–37 months). The median age at diagnosis is in the sixth and seventh decade of life with several studies demonstrating a slight male predominance. In the largest series of WHO-defined aCML, shorter survival was associated with older age (>65 years), female gender, leukocytosis >50 K/uL, and the presence of circulating precursors. The natural history of aCML is characterized by increasing leukemic cell burden, organomegaly, anemia, and bone marrow failure with transformation to acute myeloid leukemia (AML) in 30–40% of cases.

The following are the current WHO-defined diagnostic criteria for atypical CML:

• Peripheral leukocytosis >13 K/uL due to increased neutrophils and their precursors (accounting for greater than >10% of leukocytes).
• Dysgranulopoiesis, which may include abnormal nuclear chromatin clumping.
• Minimal or absent absolute basophilia (basophils <2% of leukocytes).
• Minimal or absent absolute monocytosis (monocytes <10% of leukocytes).
• Hypercellular bone marrow with myeloid proliferation and granulocyte dysplasia, with or without dyserythropoiesis or dysmegakaryocytopoiesis.
• Less than 20% blasts in the blood or bone marrow.
• Absence of BCR-ABL1 or PCM1-JAK2 fusion genes, PDGFRA, PDGFRB, or FGFR1 rearrangements.
• The WHO diagnostic criteria for BCR/ABL1-positive chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, or primary myelofibrosis are not met

These diagnostic criteria help distinguish aCML from other entities in the differential diagnosis, which should include a leukemoid reaction in addition to the neoplastic entities listed above.  The minimal absolute monocytosis and presence of >10% immature myeloid cells with dysplasia in aCML helps to distinguish aCML from CMML and CNL, respectively.

As noted above, the diagnostic evaluation of patients with suspected aCML should include conventional cytogenetics (karyotype), fluorescence in situ hybridization (FISH), and mutational analysis. The frequency of chromosomal abnormalities in aCML is widely variable, ranging from 20-88% in several series. Recurrent karyotypic abnormalities include aneuploidy in one third of patients. Trisomy 8 is most commonly found, but loss of chromosomes 5 and 7, del (20q), and isochromosome i(17)(q10) may also be seen. Driver mutations associated with MPNs (including mutated JAK2, CALR, and MPL) are typically absent in the MDS/MPN disorders, with the exception of JAK2V617F which has been reported in approximately 4–8% of aCML cases. Given the low incidence, JAK2V617F is unlikely to be a driver mutation in the pathogenesis of aCML. The largest category of somatically mutated genes in MDS/MPN, especially in aCML, are mutations that activate signaling pathways and likely drive pathogenesis. The earliest mutations identified were those involving RAS (KRAS and NRAS), which mediate the MAP kinase signaling cascade, and are seen in about 10–30% of patients with aCML.

Technologic advances in mutational profiling and next-generation sequencing have begun to reveal several molecular distinctions further differentiating aCML from its MDS/MPN overlap and MPN counterparts. The molecular fingerprint of aCML appears to be heterogeneous, including recurrent somatic mutations affecting genes involved in growth factor signaling and epigenetic regulation of DNA methylation and histone modification.  The most common mutations detected in aCML include ASXL1 (20–70%), SETBP1 (25–30%), and TET2 (43%).  SETBP1 mutations show a preference for MDS/MPN overlap syndromes, especially those with del(20q), −7, and iso-chromosome i(17)(q10) abnormalities, suggesting its use as a biomarker for these syndromes. There is a strong correlation of mutated SETBP1 with mutations involving ASXL1 (a histone modification gene), suggesting a potential cooperative role in leukemic progression in aCML. Multiple studies have shown that mutated SETBP1 is associated with a more adverse clinical profile (higher WBC count, lower hemoglobin level, thrombocytopenia) and overall worse prognosis in both aCML and CMML patients, perhaps indicating this mutation is not only relevant to leukemogenesis but also an important prognostic factor for clinical decision making in these diseases. A high frequency of SRSF2 mutations (40%) was reported among a cohort of 60 patients with aCML, while its frequency has been reported variably in other studies. SRSF2 mutation appears more frequently associated with ASXL1 and SETBP1 mutations in aCML as compared to other MPN/MDS entities, including CMML. Mutations in the granulocyte-colony stimulating factor 3 receptor (CSF3R), an important cellular signaling pathway oncogene, are mostly associated with chronic neutrophilic leukemia, but also rarely present in aCML (less than 10%). Mutations in ETNK1 (ethanolamine kinase 1) have been recently described in approximately 9% of aCML patients. These mutations are less commonly found in closely related clonal diseases such as CMML, and absent in healthy donors, MPN, and MDS/MPN overlap syndromes. This recurrent somatic mutation has never before been reported in cancer and its mutated locus is highly conserved across many species suggesting a critical, yet unknown, functional role in the pathogenesis of aCML. The presence of this molecular heterogeneity may provide pathogenetic insight and a rationale for development of novel therapeutic agents against these targets in patients with aCML.

There is currently no standard of care for the treatment of aCML. The challenges in the management of this relatively rare MDS/MPN stem from its heterogeneous clinical and genetic features, high rate of transformation to AML, and absence of sufficient randomized clinical trial data to support treatment recommendations. As with other MDS/MPN entities, participation in therapeutic clinical trials whenever possible is recommended given the absence of established treatment guidelines. When clinical trials are unavailable, the current treatment approach incorporates current strategies used for MDS and MPN including use of hematopoietic stem cell transplantation, conventional chemotherapy, and adjunctive agents for disease cytoreduction.

Several experimental targeted therapies have emerged based on insights from NGS data. Given the poor prognosis of aCML, eligibility for allogeneic HSCT should be one of the first considerations in the treatment algorithm as this is the only potentially curative treatment strategy for this disease. Current data supporting the use of HSCT remains extremely limited due to the low disease incidence. Until recently, most of this data was based on series of patients with heterogeneous MDS/MPNs showing overall survival (OS) and disease free-survival (DFS) rates at 2–5 years of 42–47%, and 37–52%, respectively.  For those ineligible for HSCT or clinical trials, or those in need of immediate treatment from highly symptomatic disease (e.g. leukocytosis, anemia, splenomegaly, constitutional symptoms), strategies used previously in MDS and/or MPN hydroxyurea, interferon-alpha, erythropoiesis stimulating agents, and hypomethylating agents (e.g. azacitidine and decitibine), have been adopted to induce palliative disease cytoreduction in aCML. The most commonly administered adjunct therapy is hydroxyurea typically utilized to control leukocytosis or symptomatic splenomegaly. There have been multiple reports of both hydroxyurea and IFN-α inducing complete and partial hematologic response in aCML; however, the duration of response is usually limited to months.

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References

• Arber DA, Orazi A, Hasserjian R, Borowitz MJ, Le Beau MM, Bloomfield CD, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016;127(20):2391–406.
• Aujla A, Linder K, Iragavarapu C, Karass M, and Liu D. SRSF2 mutations in myelodysplasia/myeloproliferative neoplasms. Biomarker Research (2018) 6:29.
• Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick H, et al. The chronic myeloid leukaemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American-British cooperative leukaemia group. Br J Haematol 1994;87(4):746–54.
• Dao K-HT, Tyner JW. What's different about atypical CML and chronic neutrophilic leukemia? Hematology Am Soc Hematol Educ Program. 2015;2015:264-271.
• Dao, K. T., Tyner, J. W. & Gotlib, J. Recent progress in chronic neutrophilic leukemia and atypical chronic myeloid leukemia. Curr. Hematol. Malig. Rep.12,432–441 (2017).
• Gelsi-Boyer V, Brecqueville M, Devillier R, Murati A, Mozziconacci, MJ, Birnbaum D. Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases. J Hematol Oncol. 2012;5:12.
• Gotlib J, Maxson JE, George TI, Tyner JW. The new genetics of chronic neutrophilic leukemia and atypical CML: implications for diagnosis and treatment. Blood. 2013;122(10):1707-1711.
• Koldehoff M, Beelen DW, Trenschel R, et al. Outcome of hematopoietic stem cell transplantation in patients with atypical chronic myeloid leukemia. Bone Marrow Transplant. 2004;34(12):1047-1050.
• Makishima H, Yoshida K, Nguyen N, et al. Somatic SETBP1 mutations in myeloid malignancies. Nat Genet. 2013;45(8):942-946.
• Maxson JE, Gotlib J, Pollyea DA, et al. Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML. N Engl J Med. 2013;368(19):1781-1790.
• Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al.WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. Lyon: International Agency for Research on Cancer (IARC), 2008.
• Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
• Wang SA, Hasserjian RP, Fox PS, et al. Atypical chronic myeloid leukemia is clinically distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms. Blood. 2014;123(17):2645-2651.

Case History / 14

Angela Wu / GU Pathology

Clinical History:
53-year-old woman with a 3.8 cm renal mass.

Case History / 15

Drew Pratt / Neuropathology

Clinical History:
A 54-year-old female presents with a two-week history of worsening headache and two-day history of worsening gait. Head CT showed a large heterogeneously enhancing right temporal mass. MRI brain showed a large necrotic mass centered in the right temporal lobe with surrounding edema and mass effect with uncal herniation and an 8mm midline shift. She underwent craniotomy for biopsy.

Case History / 16

Jiaqi Shi / GI Pathology

Clinical History:
75-year old male presented with worsening epigastric pain, bloating, nausea, vomiting, fever, and chills. Lab tests showed CEA <1, CA19-9=4. MRI abdomen showed gastric outlet obstruction secondary to a 21 cm multilocular cystic epigastric mass of unclear origin. Biopsy diagnosis: spindle cell proliferation and low-grade epithelial proliferation worrisome for low-grade pancreatic adenocarcinoma

Case History / 17

Kathleen Cho / Gynecologic Pathology

Clinical History:
A 60-year-old woman presented with abdominal bloating and discomfort. Abdominal/pelvic CT showed a large pelvic mass, ascites, and omental caking. Following three cycles of carboplatin/Taxol neoadjuvant therapy, an exploratory laparotomy, total hysterectomy, bilateral salpingo-oophorectomy, omental biopsies, and partial colectomy were performed.

Case History / 18

Julia Dahl / Gynecologic Pathology

Clinical History:
Female infant and placenta delivered to 36-year-oldG2P2103 mother. Mother is B=, antibody screen negative. Rubella immune, and RPR negative. Other prenatal testing not available.

Female infant delivered at 36 w and 6 days (LMP, ultrasound) with recent ultrasound detecting pericardial effusion and hepatosplenomegaly. Clinical concern for hydrops fetalis.

Case History - Case 18B (Bonus case): Female infant and placenta delivered to 23-year-oldG1P1001 mother who presents with fatigue, abnormal CBC and possible gestational hypertension. Infant delivered by C-Section at 32 weeks.

Case History / 19

Andy Sciallis / Gynecologic Pathology

Clinical History:
A 45-year-old female with anemia and abnormal pap screening.

Case History / 20

Stephanie Skala / Gynecologic Pathology

Clinical History:
A 72-year-old woman with a history of uterine prolapse and cystocele underwent a hysterectomy.

Case History / 21

Robert H. Young / Gynecologic Pathology

Clinical History:
A 35-year-old woman was found to have a unilateral 6 cm multilobulated ovarian mass which had a tan whorled sectioned surface.

Break Out Case History / 01

Sara Abbott & Andy Sciallis / Breast Pathology

Case 1 / Clinical History: 51F with a right breast mass.
Case 2 / Clinical History: 59F with a left breast mass.
Case 3 / Clinical History: 55F with a right breast mass.
Case 4 / Clinical History: 60F with multiple right breast masses.
Case 5 / Clinical History: 63F with suspicious left breast calcifications.
Case 6 / Clinical History: 66F with an infiltrative right breast mass.
Case 7 / Clinical History: 71F with a suspicious left breast mass.
Case 8 / Clinical History: 55F with an ill-defined left breast mass.
Case 9 / Clinical History: 61F with an ill-defined right breast mass.
Case 10 / Clinical History: 71F with a history of right breast cancer metastatic to axillary lymph nodes. She had an incidental right axillary mass which was excised.
Case 11 / Clinical History: 69F with a right breast mass.
Case 12 / Clinical History: 61F with a well-defined right breast mass.
Case 13 / Clinical History: 59F with a well-circumscribed left breast mass.
Case 14 / Clinical History: 60F with a circumscribed right breast mass.
Case 15 / Clinical History: 23F with a circumscribed right breast mass.
Case 16 / Clinical History: 65F with a circumscribed right breast mass.
Case 17 / Clinical History: 57F with a fleshy but circumscribed left breast mass.
Case 18 / Clinical History: 53F with a 13.2 cm flesh left breast mass.

Break Out Case History / 02

Jeffrey Myers / Thoracic Pathology

Case 1 / Clinical History: Pre-operative diagnosis: Cancer of bronchus right upper lobe.

Case 2 / Clinical History: A 68-year-old woman was referred for ongoing care for stage IIIB (cT4 N3 MO) lung adenocarcinoma. Her story began in January 2016 when a CT scan of her chest showed a 3.2 cm right upper lobe lung mass with tracheal invasion. A core needle biopsy showed a TTF-1 positive adenocarcinoma. She underwent concurrent chemoradiation resulting in a partial response (RUL mass reduced to 1.8 cm with no adenopathy). Follow-up CT at 2 years was stable showing no significant change. Follow-up PET/CT scan performed 5 months later showed an FDG-avid enlarging RUL mass (4.7 cm) and an FDG-avid LUL nodule. Biopsy of her RUL mass (slide A) showed only apical cap and was negative for malignancy. Repeat PET/CT scan 3 months later (January 2019) showed interval progression of her right apical opacity for which she underwent wedge resection (slide B).

Case 3 / Clinical History: A 66-year-old man with radiologic findings consistent with interstitial lung disease. His past medical history is significant for right-sided spontaneous pneumothorax in December 2018 for which he underwent VATS with blebectomy and talc pleurodesis. He also has a history of tobacco abuse. On physical examination, his lungs were described as clear to auscultation. A CT scan of his chest reported, "Findings consistent with chronic interstitial lung disease with bilateral bulla and peripheral honeycombing in both lung bases."

Case 4 / Clinical History: A 44-year-old man presented with abdominal pain, weight loss, and abdominal distention. His past medical history includes no previous malignancies. A CT scan of his chest, abdomen and pelvis showed adenopathy throughout with omental caking and a small right pleural effusion. He had no masses in his organs.

Case 5 / Clinical History: A 31-year-old woman presented with exertional dyspnea. Her past medical history is most significant for common variable immunodeficiency (CVID), managed with IVIG. She is a former smoker. A CT scan of her chest performed with contrast was described as showing "patchy interstitial alveolar nodular type infiltrates" and splenomegaly.

Case 6 / Clinical History: A 42-year-old woman presented for ongoing management of multiple lung nodules. Her past medical history is significant for previous resections of histologically similar tumors from her uterus and elsewhere for which she carried a diagnosis of a leiomyoma with disseminated leiomyomatosis. Others had proposed a diagnosis of metastatic low-grade leiomyosarcoma. Her oncologist was requesting comprehensive molecular profiling of her lung tumors.

Case 7 / Clinical History: A 78-year-old man presented with new-onset seizures and was discovered to have clinical stage IV lung cancer with brain metastases. A CT scan of his chest showed a 4.4 cm spiculated lesion in his right upper lobe and 1.1 cm. spiculated nodule in his left upper lobe.

Case 8 / Clinical History: A 55-year-old woman initially presented in February of this year with increasing shortness of breath. She was diagnosed with interstitial lung disease for which she was started on steroids. Serologic studies were negative for connective tissue disease-associated markers. Her symptoms progress and were not relieved by supplemental oxygen. Her chest x-ray and CT scan confirmed extensive chronic interstitial lung disease with marked progression.

Break Out Case History / 03

Scott Owens / GI Pathology

Case 1 / Clinical History: 42-year-old man with a history of fatigue, hepatitis C, elevated liver enzymes, and a liver lesion.

Case 2 / Clinical History: 62-year-old man with multiple polyps found on screening colonoscopy.

Case 3 / Clinical History: 55-year-old man with abnormal MRI findings in the abdomen, suggestive of “mesenteric panniculitis”. Patchy abnormalities found in jejunal mucosa on endoscopy.

Case 4 / Clinical History: 61-year-old man with rectal polyp found on screening endoscopy.

Case 5 / Clinical History: 40-year-old woman with chronic diarrhea and an endoscopically normal colon.

Case 6 / Clinical History: 41-year-old woman with diabetes and gastroparesis, found to have elevated liver enzymes (AST 156, ALT 206, alkaline phosphatase 442). Weakly positive ANA.

Case 7 / Clinical History: 54-year-old woman with a rectal mass.

Case 8 / Clinical History: 69-year-old man with a history of prostate cancer and obstructive jaundice found to have a mass around the bile duct.

Case 9 / Clinical History: 66-year-old man with abnormal CT findings in the GI tract. There were ulcers in the cecum and at the splenic flexure. Past history of a lung transplant.

Case 10 / Clinical History: 83-year-old woman who presented with gastric outlet obstruction. An antral mass was found and resected. This is a regional lymph node from that resection.

Case 11 / Clinical History: 80-year-old man with gastric resection for an invasive adenocarcinoma found in a polyp in the gastric body. These sections are from the stomach around the polypectomy site.

Case 12 / Clinical History: 90-year-old woman with a “slowly growing anal polyp.”

Case 13 / Clinical History: 59-year-old man with vague right lower quadrant and pelvic pain, cramping, diarrhea, weight loss, and anemia. Abdominal lymphadenopathy and splenomegaly were seen on CT scan and the duodenum appeared “inflamed” on endoscopy.

Case 14 / Clinical History: 53-year-old woman with a history of colon polyps and perianal inflammation. Rectal biopsy.

Break Out Case History / 04

Douglas Fullen / Dermatopathology

Cutaneous Adnexal Tumor Case Histories

Case 1 / Clinical History: 42 y.o. female with papule on her nose. DDx: R/O BCC

Case 2 / Clinical History: Nodule on the flank of a 63 y.o. man. DDx: Cyst, R/O malignancy

Case 3 / Clinical History: Nodule on the eyelid of a 65 y.o. female. DDx: Cyst vs Neoplasm

Case 4 / Clinical History: Nodule on the cheek of a 55 y.o. male. DDx: R/ONMSC

Case 5 / Clinical History: Lesion on the cheek of a 42 y.o. female. DDx: SK, R/O BCC

Case 6 / Clinical History: Tumor on the trunk of a 75 y.o. female. DDx: BCC vs SCC vs other

Case 7 / Clinical History: Yellowish papueon the left cheek of a 59 y.o. male. DDx: Sebaceous hyperplasia vs sebaceous neoplasm vs BCC vs nevus

Case 8 / Clinical History:  Nodule on the finger of a 47 y.o. male. DDx: NUB, cyst

Case 9 / Clinical History: Scalp tumor nodule in a 77 y.o. woman. No prior history of cancer. DDx: R/O malignancy

Case 10 / Clinical History:  Long-standing nodule on the scalp of a 38 y.o. male. DDx: R/O neoplasm or cyst.

Break Out Case History / 05

Lauren Smith & Anamarija Perry / Hematopathology

Case 1 / Clinical History: 23-year-old male with cervical lymphadenopathy

Case 2 / Clinical History: 31-year-old male with cervical lymphadenopathy

Case 3 / Clinical History: 34-year-old male with an axillary mass

Case 4 / Clinical History: 23-year-old male with inguinal lymphadenopathy

Case 5 / Clinical History: 3-year-old female with cervical lymphadenopathy

Case 6 / Clinical History: 67-year-old male with diffuse lymphadenopathy and pancytopenia

Case 7 / Clinical History: 31-year-old male with nasal mass

Case 8 / Clinical History: 68-year-old female with axillary lymphadenopathy

Case 9 / Clinical History: 55-year-old female with diffuse lymphadenopathy

Case 10 / Clinical History: 82-year-old male with hepatosplenomegaly and pancytopenia; splenectomy performed

Case 11 / Clinical History: 59-year-old female with cervical lymphadenopathy

Case 12 / Clinical History: 80-year-old male with inguinal lymphadenopathy

Case 13 / Clinical History: 58-year-old female with a mediastinal mass

Break Out Case History / 06

Tao Huang / GYN Pathology

Case 1 / Clinical History: A 56-year-old woman presented with a left ovarian mass. On gross examination, the left ovary measures 13.5 cm and is multicystic with multiple papillary excrescences on the surface and cyst lining.

H&E slides: A-Representative section of left ovarian mass B-Section of the uterine serosa C-Biopsy of peritoneum D-Biopsy of pelvic lymph node

Case 2 / Clinical History: 58-year-old woman presented with right-sided abdominal pain. A CT scan revealed a right adnexal complex cystic mass measuring 9.4 cm. She underwent TAH, BSO, pelvic and para-aortic lymphadenectomy, omentectomy, and implant biopsies.

H&E slides: A-Representative section of right ovarian mass (frozen section control) B-Representative section of right ovarian mass C-Section of uterine serosa D-GBiopsies of implants H-J Representative sections of omentum K-Section of the right fallopian tube L-Biopsy of pelvic lymph node

Case 3 / Clinical History: 57-year-old woman presented with increasing abdominal pain and MRI demonstrated a complex left ovarian complex cystic mass measuring 11 cm. She underwent TAH, BSO, pelvic and para-aortic lymphadenectomy, omentectomy.

H&E slides: A-B: Representative sections of the left ovarian mass

Case 4 / Clinical History: 49-year-old woman presented with menorrhagia and a pelvic ultrasound demonstrated multiple large fibroids with the largest one measuring 10 cm as well as a 6.5 cm right ovarian cyst. She underwent TAH and BSO. Intraoperatively, an enlarged, irregular, 20-week size uterus with normal ovaries and fallopian tubes wasnoted.

H&E slides: A-Section of the left fallopian tube and ovary B-Section of the right fallopian tube and ovary C-Additional section of the right ovary

Case 5 / Clinical history: A 63-year-old woman presented with a pelvic mass and underwent TAH/BSO with a tumor staging procedure

H&E slides: A-Representative section of the pelvic mass

Case 6 / Clinical History: 36-year-old woman underwent TAH for abdominal/pelvic pain and menorrhagia. She continued to have abdominal/pelvic pain after TAH. Two years later, she underwent a diagnostic laparoscopy, lysis of adhesions, and peritoneal biopsies. Intraoperatively, numerous peritoneal implants were found, for which pathology showed low-grade serous neoplasm. Two months later, she underwent exploratory laparotomy, BSO, omentectomy, pelvic and para-aortic lymphadenectomy with optimal debulking to no measurable disease. Intraoperatively, the fallopian tubes and ovaries were both noted to be in situ with small surface excrescences. There were also multiple small, firm peritoneal implants in the cul-de-sac extending onto the pelvic sidewalls, rectal serosa, mesorectum, and serosal surface of the distal ileum.

H&E slides: A-Section of left ovary B-Section of left ovary C-Biopsy of pelvic implant D-Biopsy of small bowel serosal implant

Case 7 / Clinical history: 71-year-old woman presented with ascites and pelvic mass. Histologically, it is a low-grade serous carcinoma, arising from a serous borderline tumor with micropapillary architecture, involving bilateral ovaries and fallopian tubes.

H&E slides: A-Sections taken from a well-circumscribed nodule of the ovarian low-grade serous carcinoma

Case 8 / Clinical history: 46-year-old woman presented with an abdominal mass. She underwent TAH, BSO, and omentectomy. On gross examination, the bilateral ovarian surfaces show multiple implants measuring up to 3 cm. Omentum also shows multiple nodules measuring up to 7 cm.

H&E slides: A-Representative section of the ovary