A Med Tech Gives a TEDx Talk

Hello again everyone!

After a lot of positive responses and sharing on social media, my article last month got lots of people talking about annual meetings and how great they are for networking, learning, and advancing our profession. Not too long after the ASCP Annual Meeting in Phoenix, I was back in my Manhattan apartment working on my speech and graphics for a real life TEDx session hosted at my medical school.

Let’s pause here: if you either haven’t heard of the TED/TEDx brand or if you binge watch their 18 minute videos and want more links to watch now, now, now!

TED is a non-profit organization whose mission is to share “ideas worth spreading.” They’re about 35 years old and based in NYC stateside, and Vancouver in Canada. Basically, over the last few decades they hold conferences at those flagship sites called “TED talks” where selected speakers present on a myriad of topics. TEDx conferences are officially licensed but off-site events which operate under TED protocol and guidelines. There have even been spin-off conferences like TED MED, which focus solely on healthcare.

Image 1. What’s a TEDx talk? Basically, an off-site, officially sanctioned, “idea sharing” conference.

Some of the students at AUC School of Medicine, organized such a conference with official TED licensing and recruited me to join their list of speakers to deliver talks on their chosen theme: resilience. Officially called TEDxAUCMed, this conference included community members, students, artists, activists, and more discussing the human capacity for resilience in ways not commonly discussed. “Weathering the Storm” was the official event title, as the school located in the island nation of St. Maarten displays daily resilience especially since being hit by Hurricane Irma in 2016. Among their list of incredible speakers, I was humbled to be included! I titled my talk “Unrecognizable Medicine” and wanted to deliver a talk to students, clinicians, and those of us in medicine witnessing first-hand a tidal wave of new technologies and paradigms that redefine the way we discuss health. Oh, and since I’m a huge fan of #GraphicMedicine more and more each day, I hit that hashtag hard and decided to illustrate my whole talk!

Image 2. Title Card from my TEDx talk.

So what did I talk about, exactly…and what’s the big deal? I’m not going to re-hash my presentation for you in text—that’d be boring, and I’m obviously going to put a link at the bottom for you to watch it yourself. I got you, lab fam! But essentially, what I set up was a three-tiered template to assess and navigate that tidal wave of tech. Tools, skills, and strengths—three things inherent to the practice of medicine in any specialty.

Image 3. Red back-ligting. So intense. Thanks for coming to my TEDx Talk, literally!

There are untapped topics in medicine which are looming over the horizon. As medicine continues to evolve and change, the problems we face and the needs we must meet will become moving targets. New specialties will emerge, and new technologies will replace centuries old tools we cling to today. A shift in thinking is both proactive and healthy in a profession that mandates our commitment to preserving health and quality of life. I have spent years battling stereotypes in medicine and hope to challenge the fabric that places individuals in professional or academic boxes. Fresh first-years at some schools are already using point-of-care ultrasounds (POCUSes) instead of stethoscopes—which student sounds like they have better info on morning rounds, a student who maybe kinda-sorta heard some non-descript murmur, or a mini-pocket echocardiogram with an ejection fraction of 45%? Stereotypes have too long shaped the way students choose specialties, equating some areas to colloquial high school cliques! No offense to orthopedics or dermatology. Troponins used to be something you could hang your white coat on, but not anymore. What do you do with a new 5th generation Trop of 39 with a delta of 18? ACS or acute MI? Cancer therapy is exploding with personalized treatments being added every day! Any student right now would impress their heme/onc attending on rounds if they suggested PDL-1 and other immunotherapy testing for patients with newly diagnosed lung cancers. *Deep breath*

Ok. My point is, tomorrow’s medicine is going to have a lot of different therapies, tools, and even vocabulary that schools may never catch up with. How do you prepare for this explosion of knowledge? You look to yourself to take an inventory of your strengths and use those to guide your clinical sails. Addressing stereotypes head-on, learning on the spot, dealing with complex identities in your patients, and always practicing with compassion will lend itself to staying ahead and staying fulfilled.

Image 4. If you’re drawing cartoons of pathologists for an educational series, you probably make them look like you. Or in this case me, I guess. Keep an eye out for my #PathDoodles on social media!

Pretty heavy stuff right? But there’s something else that caught my attention in reflection on the TEDx talk… I’ve searched the TED library of videos, and while there are plenty of doctors, scientists, and pioneers in research discussing medical ideas, I haven’t seen any medical laboratory scientists. If you find any, please correct me. But, as I understand it, it’s just me. And that’s something special.

Image 5. My wife and I check-in for rehearsal at the TEDxAUCMed conference in sunny St. Maarten.

There’s a culture shift in our profession, and a lot of us are talking about it. Pathology and laboratory medicine are stepping out from behind the healthcare curtain and asserting itself as a champion for patients, truth, and the importance of data-driven medicine. Not only do I talk to groups of folks every time I get a stage, but I use social media to reach clinicians and patients! Yes, I’m one of few medical students-turned-residency applicants who didn’t change their name to hide their online presence for the winter. But instead of a secret twitter hibernation, I’ve used social media as a tool to network, engage, and connect.

One of my favorite new projects is something I call #PathDoodles where I break down the aspects of pathology and some specialty topics for those outside of medicine (and sometimes just outside our profession). I’ve already covered things like “what is pathology?” and the importance of autopsies, the role of medical laboratory scientists, and I continue to add more regularly!

Image 6. One of a growing list of #PathDoodles.

There’s a culture shift in our profession, and a lot of us are talking about it. Pathology and laboratory medicine are stepping out from behind the healthcare curtain and asserting itself as a champion for patients, truth, and the importance of data-driven medicine. Not only do I talk to groups of folks every time I get a stage, but I use social media to reach clinicians and patients! Yes, I’m one of few medical students-turned-residency applicants who didn’t change their name to hide their online presence for the winter. But instead of a secret twitter hibernation, I’ve used social media as a tool to network, engage, and connect.

One of my favorite new projects is something I call #PathDoodles where I break down the aspects of pathology and some specialty topics for those outside of medicine (and sometimes just outside our profession). I’ve already covered things like “what is pathology?” and the importance of autopsies, the role of medical laboratory scientists, and I continue to add more regularly!

Follow me on Twitter (@CEKanakisMD) and check out my TEDx talk:

My talk begins at 5:00:00. Enjoy!

Constantine E. Kanakis MD, MSc, MLS (ASCP)CM completed his BS at Loyola University Chicago and his MS at Rush University. He writes about experiences through medical school through the lens of a medical lab scientist with interests in hematopathology, molecular, bioethics, transfusion medicine, and graphic medicine. He is currently a 2020 AP/CP Residency Applicant and actively involved in public health and education, advocating for visibility and advancement of pathology and lab medicine. Follow him on Twitter @CEKanakisMD

Surgical Pathology Case Study: A 43 Year Old Female with a Lung Nodule Noted on Imaging Following Chest Congestion

Case History

The patient is a 43 year old woman who experienced chest congestion and presented to her local physicians office. A chest X-ray was ordered and demonstrated a lung abnormality. A follow-up CT scan confirmed a 1.9 cm smoothly marginated nodule in the upper lobe with no adenopathy and a normal liver and adrenal glands. The nodule was mildly hypermetabolic on PET scan. A bronchoscopy was performed, which was non-diagnostic. Two subsequent CT scans demonstrated no change in the size of the nodule. Overall, the patient feels well and denies cough, hemoptysis, dyspnea on exertion, and weight loss. Due to the suspicion of cancer, the patient has decided to undergo a lung lobectomy.

Diagnosis

Received in the Surgical Pathology lab for intraoperative consultation is a 30.0 x 7.2 x 2.2 cm lung lobectomy specimen. There is an attached 6.2 cm staple line, which is removed and the subjacent resection margin is inked blue. The entire pleural surface is inked black. The specimen is sectioned revealing a 2.1 x 1.7 x 1.0 cm white-tan, firm, round nodule that is 0.5 cm from the blue inked resection margin and 0.2 cm from the black inked pleural surface. The remainder of the specimen is composed of red-tan, spongy, grossly unremarkable lung parenchyma without nodules or other lesions. Photographs of the specimen are taken (Figure 1). A representative section of the nodule is submitted for frozen section and read out as “diagnosis deferred”. Representative sections of the specimen are submitted as follows:

A1FS:   Frozen section remnant

A2-A7:   Nodule, entirely submitted

A8-A10:   Grossly unremarkable lung parenchyma

Immunohistochemical stains show the epithelial cells in the lesion to be positive for CK7, TTF-1, and surfactant proteins A and B which supports these cells to be type 2 pneumocytes (all controls are appropriate). Based on the immunohistochemical stains and routine H&E slides, the case was signed out as a sclerosing pneumocytoma

Image 1. Gross presentation of the well-defined, round sclerosing pneumocytoma.

Discussion

Sclerosing pneumocytoma (SP) is a rare, benign pulmonary tumor that was first described in 1956 as a vascular tumor, but has since been found to be of primitive respiratory epithelium origin. In the past, SP has also been referred to as sclerosing hemangioma, pneumocytoma, and papillary pneumocytoma, but the 2015 World Health Organization classification of lung tumors states that the agreed upon term for this tumor should be a sclerosing pneumocytoma. SP is commonly seen in middle aged adults, with a female to male ratio of 5:1. There is no racial bias. Patients are usually asymptomatic, with the tumor incidentally found on screening chest radiographs. If the patient was to present with any symptoms, they would usually include a cough, hemoptysis and chest pain. Radiographically, SP appears as a solitary, well-defined, homogenous nodule along the periphery of the lung.

Grossly, most SPs appear as a solitary, firm, well-circumscribed, yellow-tan mass generally arising along the periphery of the lung. The majority of these tumors appear within the lung parenchyma, but there have been cases reported of endobronchial and pleural based SP tumors. Multifocal unilateral tumors and bilateral tumors are uncommon.

Histologically, SP consists of two epithelial cell types: surface cells and round cells. Surface cells are cuboidal, resembling type II pneumocytes, with finely stippled nuclear chromatin, indistinct nuclei, occasional nuclear grooves, and inclusions. The stromal round cells will have bland oval nuclei with coarse chromatin and eosinophilic cytoplasm (Figure 2). Both the surface cells and round cells will have a low mitotic rate, but can have moderate to marked nuclear atypia. Ciliated bronchial epithelium is often identified in the tumor. There are four architectural patterns identified within SP: papillary, sclerotic, solid and hemorrhagic, with over 90% of SPs displaying three of the patterns, and all of the tumors containing at least two of the patterns.

  • Papillary pattern: Complex papillae composed of surface cells covering a stroma of round cells
  • Sclerotic pattern: Papillae containing hyalinized collagen, either in solid areas or along the periphery of hemorrhagic areas (Figure 3)
  • Solid pattern: Sheets of round cells bordered by surface cells
  • Hemorrhagic pattern: Large blood filled spaces
Image 2. Photomicrograph demonstrating the cuboidal surface cells and round stromal cells.
Image 3. Photomicrograph of the papillary and sclerotic architectural patterns.

Immunohistochemical stains can be helpful in the diagnosis of SP, with both the surface cells and round cells exhibiting expression of thyroid transcription factor 1 (TTF-1) and epithelial membrane antigen (EMA). It should be noted that TTF-1 is also used for the diagnosis of pulmonary adenocarcinoma, increasing the risk of misdiagnosing SP. The surface cells will also express both pancytokeratin (AE1/AE3) and Napsin A, with the round cells being negative for AE1/AE3, but having a variable expression of cytokeratin 7 and the low molecular weight cytokeratin (CAM 5.2). Molecular pathology has demonstrated a frequent loss of heterozygosity at 5q, 10q and 9p, and an allelic loses at p16 in the surface and rounds cells. Although the immunohistochemical stains and molecular pathology results can be very helpful, diagnosis of a SP is still largely based on routine H&E slides showing the two epithelial cell types and four architectural patterns.

Electron microscopy will show abundant lamellar bodies similar to those in type II pneumocytes in the surface cells. Round cells will lack the lamellar bodies and instead will contain variably-sized electron-dense bodies that have been thought to represent the different stages of lamellar body maturation.

The differential diagnosis for SP includes a variety of benign and malignant neoplasms, which can be difficult to distinguish on cytology, small biopsies and intraoperative consultations. The cytologic features include moderate to high cellularity with a bloody background and foamy macrophages, occasional nuclear pleomorphism in the round cells, absent mitotic figures, and occasional necrosis with cholesterol clefts and calcifications. In the case of small biopsies, making a diagnosis of SP can be difficult if the papillary pattern is highly prevalent without one of the other three patterns present. With intraoperative consultations, the frozen section artifact can make it difficult to appreciate the two epithelial cell types or the four architectural patterns. The gross examination, as well as the radiographic findings of a well-circumscribed tumor can help point the Pathologist to favoring a benign neoplasm over a malignant one. The benign neoplasms that should be considered in the differential diagnosis include:

  • Clear cell tumor, which will have clear cells with scant stroma, thin-walled vessels and a strong expression of HMB-45
  • Pulmonary hamartoma, which will have a combination of cartilage, myxoid stroma, adipose tissue and trapped respiratory epithelium
  • Hemangiomas, which are rare in the lung, and will lack epithelial cells and contain either a cavernous or capillary morphology

The malignant neoplasms that should be considered in the differential diagnosis include:

  • Bronchioalveolar carcinoma, which can have a papillary pattern, but will not contain the two epithelial cell types and combination of the four architectural patterns
  • Metastatic papillary thyroid carcinoma, which is distinguished from SP by the presence of the characteristic Orphan Annie nuclei
  • Metastatic renal cell carcinoma, which will contain nuclear atypia and striking vascularity
  • Carcinoid, which will contain organoid and ribbon-like growth patterns

Currently, with the benign nature of SP, surgical excision is the preferred treatment choice to cure the patient. There have been cases reported of lymph node metastasis and recurrence, but neither of these appear to effect the prognosis. This just helps to highlight the need for a multidisciplinary approach to this benign tumor.

References

  1. Hisson E, Rao R. Pneumocytoma (sclerosing hemangioma), a Potential Pitfall. Diagn Cytopathol. 2017;45(8):744-749
  2. Keylock JB, Galvin JR, Franks TJ. Sclerosing Hemangioma of the Lung. Arch Pathol Lab Med. 2009;133(5):820-825.
  3. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 2015;10(9):1243-1260.
  4. Wu R. Sclerosing Pneumocytoma (Sclerosing Hemangioma). Pathology Outlines. http://www.pathologyoutlines.com/topic/lungtumorsclerosingheman.html. Revised February 19, 2019. Accessed June 6, 2019.

-Cory Nash is a board certified Pathologists’ Assistant, specializing in surgical and gross pathology. He currently works as a Pathologists’ Assistant at the University of Chicago Medical Center. His job involves the macroscopic examination, dissection and tissue submission of surgical specimens, ranging from biopsies to multi-organ resections. Cory has a special interest in head and neck pathology, as well as bone and soft tissue pathology. Cory can be followed on twitter at @iplaywithorgans.

Surgical Pathology Case Study: A 3 Year Old Male with a Suspicious Lesion on Imaging Following an Injury

Case History

The patient is a 3 year old male with no significant past medical history who presented to the ED with left lower extremity pain for 24 hours after falling while playing with family members. The patient’s mother was present at bedside providing the history, but was not present at the time of the fall. It is unclear how the patient injured his ankle, but family members noticed the child grabbing his ankle and suspected that he may have twisted it. After the fall, the patient was unable/unwilling to ambulate on the ankle. There is no history of fractures or cancer.

An x-ray and subsequent MRI were ordered of the ankle which demonstrated an expansile lytic lesion involving the metaphysis of the distal tibia measuring approximately 3.4 x 2.2 cm (Figure 1 and 2). The margins of this lesion are indistinct, and there is cortical irregularity at the anterior and lateral aspect of the distal metaphysis of the tibia, likely representing a pathologic fracture. The differential diagnosis includes infection, aneurysmal bone cyst, nonossifying fibroma, osteoblastoma and histiocytosis.

The patient and family then followed up with Orthopedics, who proceeded to perform a biopsy of the lytic lesion in order to determine the nature of the lesion. The results are below.

Figure 1. Xray of the distal tibia demonstrating the lesion.
Figure 2. MRI demonstrating the lytic lesion involving the metaphysis of the distal tibia.

Diagnosis

Received fresh for intraoperative consultation is a 1.1 x 0.6 x 0.5 cm aggregate of white-tan soft tissue fragments. Half of the tissue fragments are frozen and read out as “spindle cell proliferation. Consideration of low-grade vasoformative lesion. Defer to permanent,” with 3 pathologists consulting on the diagnosis. The remainder of the tissue not submitted for frozen section, as well as the entirety of a second container from the same lesion, is submitted for routine processing.

On microscopy, the biopsies demonstrate a moderately cellular proliferation of fasciculated spindle cells in a collagenous to myxoid stroma. Nuclei are predominantly oval with variably fine to granular chromatin. Many cells have moderate amounts of tapering eosinophilic cytoplasm, resembling strap cells. Inflammatory cells and osteoclast-like giant cells are admixed (Figure 3 and 4). Immunohistochemical stains demonstrate lesional spindle cells to be positive for CD31, ERG, and FLI1. AE1/AE3 and CAM5.2 highlight rare lesional spindle cells. SMA stains some stellate spindle cells, favored to represent associated myofibroblasts. Desmin, MDM2, CDK4, ALK, and S100 are negative in plump lesional cells (Figure 5 and 6). Overall, the features are consistent with pseudomyogenic hemangioendothelioma, a rare vascular tumor. Although more commonly present in soft tissue, primary bone cases have been reported. These neoplasms have some risk for local recurrence, but only rarely distant metastasis. A portion of tissue was sent to the University of Nebraska Medical Center to evaluate for a characteristic gene rearrangement (SERPINE1-FOSB) that is present in at least a subset of pseudomyogenic hemangioendotheliomas. This was negative.

The lesion was then curettaged by the surgical team.The patient and his family had two follow up office visits with the Orthopedics department. The first one, a week after surgery, was unremarkable. The second visit, two weeks after surgery, was notable for the patient developing a cutaneous rash on both arms and chest. Due to literature citing that these tumors generally arise in the soft tissue, the clinician suggested that the patient and family follow up with pediatric dermatology to ensure that this new rash is not related to the pseudomyogenic hemangioendothelioma. Unfortunately due to insurance, the patient and family had to see a dermatologist at a different institution, and no further visits have taken place.

Figure 3. Photomicrograph of the strap-like cells with tapering eosinophilic cytoplasm , and osteoclast-like giant cells.
Figure 4. Higher power photomicrograph demonstrating the appearance of the strap-like cells with tapering eosinophilic cytoplasmFigure 4.

Discussion

Pseudomyogenic hemangioendothelioma (PHE) is a rare vascular tumor that most commonly arises in the skin and soft tissues of the extremities. It is usually multifocal, appearing in multiple tissue planes, such as the mucosa, dermis, subcutis and skeletal muscle, in a variety of different anatomic sites. Although even less common, PHE can also involve bone (such as this case). PHE has a male predilection, typically appearing in the second to fourth decades of life. Of the most common symptoms that the patient presents with, pain appears to top the list, although it should be stated that only about half of the patients experience pain.

Grossly, skin and soft tissue PHE tumors appear firm, ill-defined and gray-white. When they involve bone, they appear as multiple discrete, pink-tan to dark brown hemorrhagic tumors with surrounding sclerosis, ranging from 0.1 to 6.5 cm in greatest dimension.

Histologically, PHE demonstrates plump spindle and rhabdomyoblast-like cells with densely eosinophilic cytoplasm that grows in sheets and fascicles. The cells can be mistaken as rhabdomyoblasts because of the eosinophilic cytoplasm that pushes the nucleus to the periphery of the cell. Immunohistochemical studies are very helpful in order to determine a diagnosis of PHE. AE1/AE3, ERG, FLI-1 and CD31 are positive, whereas CD34, desmin and S100 are negative. Karyotyping has revealed a fusion of genes SERPINE1-FOSB that corresponds to the recurrent translocation t(7;19)(q22;q13). In this case, the SERPINE1-FOSBgene rearrangement was negative, but could possibly be due to a variant fusion gene.

Making a histologic diagnosis can be difficult for a Pathologist, due to the wide variety of differential diagnoses that will need to be excluded first.

The differential diagnosis for a cutaneous tumor includes:

  • Cellular benign fibrous histiocytoma (lacks rhabdomyoblast-like cells and neutrophilic infiltrates, contains mitotic figures, and is negative for cytokeratin and CD31)
  • Spindle cell squamous cell carcinoma (usually in sun-damaged skin, with nuclear atypia and negative endothelial markers)
  • Epithelioid sarcoma (negative INI1, positive EMA and CD34, and a nodular architecture with central necrosis and more nuclear atypia)

The differential diagnosis for soft tissue tumors include:

  • Epithelioid sarcoma (see above)
  • Epithelioid hemangioendothelioma (usually intracytoplasmic vacuoles, positive CD34 and CAMTA1, and a t(1;3)(p36.3;q25) translocation resulting in WWTR1-CAMTA1 gene fusion)
  • Epithelioid angiosarcoma (vasoformative architecture with sheet-like pattern, nuclear atypia, high nuclear grade, frequent mitosis and irregular vascular channels)

 The differential diagnosis for bone tumors includes:

  • Epithelioid hemangioma (lacks rhabdomyoblast-like cells)
  • Giant cell tumor (lacks rhabdomyoblast-like cells and fascicles of spindle cells)
  • Osteoblastoma (lacks rhabdomyoblast-like cells and fascicles of spindle cells)

In a study by Inyang et al, when PHE involved bone, imaging would demonstrate multiple to innumerable discontinuous tumors throughout the affected bone, involving the cortex and/or medullary cavity of the epiphysis, metaphysis, or diaphysis. On x-ray and computed tomography, the lesions appeared as well circumscribed, lobulated and lytic, with a sclerotic rim on some of the lesions. On magnetic resonance imaging, T1-weighted images would appear dark, and T2-weighted images would appear hyperintense.

PHE has a tendency to recur locally, but rarely develops distant metastases. Since PHE presents as a multifocal disease and can be easily confused for a distant metastasis, care needs to be taken to ensure that a diagnosis of PHE is not overlooked.

Surgical ablation and excision is the standard treatment for a patient with PHE, with a few cases noted of patients being treated with radiotherapy and/or adjuvant chemotherapy, in addition to surgery. Everolimus and sirolimus have recently been found to be effective in cases of patient with PHE that had metastatic and relapsing multifocal PHE.

Figure 5. Immunohistochemical stains (part 1 of 2)
Figure 6. Immunohistochemical stains (part 2 of 2)

References

  1. Hornick JL, Fletcher CDM. “Pseudomyogenic Hemangioendothelioma: A Distinctive, Often Multicentric Tumor With Indolent Behavior.” Am J Surg Pathol. 2011; 35: 190201.
  2. Inyang A, et al. “Primary Pseudomyogenic Hemangioendothelioma of Bone.” Am J Surg Pathol. 2016; 40: 587598.
  3. Pradhan D. “Pseudomyogenic hemangioendothelioma of skin, bone and soft tissue; a clinicopathological, immunohistochemical, and fluorescence in situ hybridization study.” Hum Pathol. 2018; 71: 126134.
  4. Sugita S, Hirano H, Kikuchi N, et al. Diagnostic utility of FOSB immunohistochemistry in pseudomyogenic hemangioendothelioma and its histological mimics. Diagn Pathol. 2016;11(1):75. Published 2016 Aug 11. doi:10.1186/s13000-016-0530-2

-Cory Nash is a board certified Pathologists’ Assistant, specializing in surgical and gross pathology. He currently works as a Pathologists’ Assistant at the University of Chicago Medical Center. His job involves the macroscopic examination, dissection and tissue submission of surgical specimens, ranging from biopsies to multi-organ resections. Cory has a special interest in head and neck pathology, as well as bone and soft tissue pathology. Cory can be followed on twitter at @iplaywithorgans.

Surgical Pathology Case Study: A 2.5 Year Old Male Who Presents with Jaundice and Pruritus

Case History

The patient is a 2.5 year old male who is being evaluated for a liver transplant versus biliary diversion surgery. The patient was born at 2 kilograms and went home with mom one week after birth. The patient was readmitted back to the hospital for evaluation of jaundice and since then the patient has been intermittently hospitalized for episodes of worsening jaundice, acholic stools, scleral icterus, and pruritus. At 5 months of age, the patient was diagnosed with progressive familial intrahepatic cholestasis, type 2, and was placed on the liver transplant list. As a result of the liver failure, the patient has developed coagulopathy, hypocalcemia resulting in seizures, and pruritus. The family history is significant for no known congenital liver diseases.

Table 1. Pertinent lab findings.

The father was worked up for living donation and was found to be a suitable donor, and is donating the left lateral segment of his liver.

Diagnosis

Received in the Surgical Pathology laboratory is a 700 gm, 23.5 x 14.5 x 3.5 cm explanted liver with an attached 4.5 x 1.2 x 0.4 cm gallbladder. The liver specimen has a smooth, green-red liver capsule without any grossly identifiable nodules or lesions (Image 1). The gallbladder has a yellow-pink external surface and is opened to reveal a 1.5 x 0.7 x 0.4 cm dark brown stone with a small amount of brown-yellow bile fluid. The liver is sectioned to reveal a smooth green-red cut surface (Image 2). No lesions are identified and minimal hilar structures are included with the specimen. Portions of the specimen have been taken for electron microscopy and frozen for future diagnostic purposes. Submitted sections include:

Cassette 1 and 2:   Hilar structures

Cassettes 3-15:   Representative sections of liver parenchyma

Cassette 16:   representative section of gallbladder

Image 1. Posterior aspect of green-tinged liver
Image 2. Cut section of liver

On microscopy, the trichrome stain highlights the presence of portal and centrilobular fibrosis, with focal bridging. However, regenerative nodule formation is not evident. The portal tracts contain sparse mononuclear cell infiltrates. Significant bile ductular proliferation is also evident, as confirmed by a CK7 immunostain. However, the native bile ducts appear unremarkable. There is also considerable hepatocellular and canalicular cholestasis in the centrilobular regions. Occasional multinucleated hepatocytes are also seen within the centrolobular zones. No steatosis is evident.

This constellation of histologic features is consistent with the clinical history of progressive familial intrahepatic cholestasis, type II.

Discussion

Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders that affects bile formation and results in cholestasis of the liver, usually beginning in infancy and childhood. There are three types of PFIC, each related to a mutation in the liver transport system genes that are involved in bile formation. PFIC type 1 (PFIC1), which is also referred to as Byler disease, is due to impaired bile salt secretion related to a ATP8B1 gene that encodes the FIC1 protein. PFIC type 2 (PFIC2), which is referred to as Byler syndrome, is due to impaired bile salt secretion (similar to type 1), but is related to the ABCB11 gene that encodes the bile salt export pump, or BSEP. PFIC type 3 (PFIC3) is due to impaired biliary phospholipid secretion that is related to a defect in the ABCB4 gene that encodes the multi-drug resistant 3 protein, or MDR3.

PFIC is suspected to be the cause of cholestasis in 10-15% of children, and is also the underlying cause of liver transplants in 10-15% of children. The exact prevalence remains unknown, but is estimated to be between 1 in every 50,000-100,000 births. PFIC1 and PFIC2 account for 2/3 of all PFIC cases, with PFIC3 making up the other 1/3. PFIC is present worldwide, and there does not appear to be a gender predilection.

The main clinical manifestation in all forms of PFIC, hence the name, is cholestasis, and will usually appear in the first few months of life with PFIC1 and PFIC2. Recurring episodes of jaundice are also present in PFIC1, whereas permanent jaundice and a rapid evolution to liver failure are characteristic of PFIC2. In PFIC3, cholestasis is noted within the first year of life in 1/3 of all cases, but rarely will be present in the neonatal period. PFIC3 can also present later in infancy, childhood or even early adulthood, with gastrointestinal bleeding due to portal hypertension and cirrhosis being the main symptoms that the patient would present with. Pruritus is severe in PFIC 1 and 2, but has a more mild presentation in PFIC3. There have been multiple cases reported of hepatocellular carcinoma that are associated with PFIC2, but there so far have not been any cases of hepatocellular carcinoma reported that are associated with PFIC3. Other signs and symptoms that may be present in PFIC1 include short stature, deafness, diarrhea, pancreatitis and liver steatosis. When examining clinical laboratory results, patients with PFIC1 and PFIC 2 will have normal serum gamma-glutamyltransferase (GGT) levels, but patients with PFIC3 will have elevated GGT levels. PFIC1 and PFIC2 can be differentiated from each other by the higher transaminase and alpha-fetoprotein levels that are found in PFIC2. When analyzing the biliary bile salt concentrations, PFIC1 will have mildly decreased levels (3-8 mM), PFIC2 will have drastically decreased levels (<1 mM), and PFIC3 will have normal levels. In addition, the biliary bile salt:phospholipid ratio and the cholesterol:phospholipid ratio will be approximately 5 times higher in PFIC3 than in normal bile, due to the biliary phospholipid levels being dramatically decreased (normal phospholipid range = 19-24%, PFIC phospholipid range = 1-15%).

Histologically, PFIC1 and PFIC 2 will have canalicular cholestasis, an absence of true ductular proliferation, and periportal biliary metaplasia of the hepatocytes. In PFIC2, these manifestations are much more worrisome with more marked lobular and portal fibrosis, and inflammation, as well as having much more pronounced necrosis and giant cell transformation (Images 3 and 4). PFIC3 will show portal fibrosis and true ductal proliferation, with a mixed inflammatory infiltrate. In addition, cholestasis can be present in the lobule and in some of the ductules that contain bile plugs. Cytokeratin staining can help confirm the ductular proliferation within the portal tract. Mild or absent canalicular staining with BSEP and MDR3 antibodies will help to diagnose PFIC2 and PFIC3, respectively.

Image 3. Photomicrograph demonstrating cholestasis, centrilobular necrosis, lobular inflammation, and giant cells (H&E)
Image 4. Photomicrograph demonstrating portal, centrilobular and bridging fibrosis (Trichrome)

A diagnosis of PFIC is based on the clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests for excluding other causes of childhood cholestasis (such as biliary atresia, Alagille syndrome, cystic fibrosis and alpha-1 antitrypsine deficiency). Ultrasonography of the liver will be normal with the exception of a possible dilated gallbladder. At the time of the liver biopsy, a portion of tissue can be submitted for electron microscopy, which in the case of PFIC, can show canalicular dilatation, microvilli loss, abnormal mitochondrial internal structures, and varying intra-canalicular accumulations of bile. PFIC1 will have coarsely, granular bile on electron microscopy, whereas PFIC2 will have a more amorphous appearance. If biliary obstruction is noted on the liver biopsy, a cholangiography will need to be performed to exclude sclerosing cholangitis. If a normal biliary tree is observed, as in PFIC, bile can be collected for biliary bile salt analysis (which was discussed earlier in the laboratory results section). Differentiating between PFIC1, PFIC2 and PFIC3 can be quite troublesome, but luckily Davit-Spraul, Gonzales, Baussan and Jacquemin proposed a fantastic schematic for the clinical diagnosis of PFIC, which is presented as Figure 1.

Figure 1. Schematic proposed for the clinical diagnosis of progressive familial intrahepatic cholestasis

Ursodeoxycholic acid (UDCA) therapy should be considered in all patients with PFIC to prevent liver damage and provide relief from pruritus. Rifampicin and Cholestyramine can help in cases of PFIC3, but have been found to provide no improvement in PFIC1 or PFIC2. In some PFIC1 or PFIC2 patients, biliary diversion can also relieve pruritus and slow disease progression. The total caloric intake should be around 125% of the recommended daily allowance. Dietary fats should come in the form of medium chain triglycerides, and care should be taken to check the patient’s vitamin levels to look for signs of vitamin deficiency. Patients with PFIC2 should be monitored for hepatocellular carcinoma, beginning from the first year of life. Ultimately, most PFIC patients develop fibrosis and end-stage liver disease before adulthood, and are candidates for liver transplantation. Diarrhea, steatosis and short stature may not improve after liver transplantation, and could become aggravated from the procedure. Hepatocyte transplantation, gene therapy or specific targeted pharmacotherapy are possible alternative therapies for PFIC, but will require more research and studies to determine whether they are viable options.

References

  1. Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis. 2009;4(1). doi:10.1186/1750-1172-4-1
  2. Evason K, Bove KE, Finegold MJ, et al. Morphologic findings in progressive familial intrahepatic cholestasis 2 (PFIC2): correlation with genetic and immunohistochemical studies. Am J Surg Pathol. 2011;35(5):687–696. doi:10.1097/PAS.0b013e318212ec87
  3. Srivastava A. Progressive Familial Intrahepatic Cholestasis. J Clin Exp Hepatol. 2013;4(1):25-36. doi: 10.1016/j.jceh.2013.10.005

-Cory Nash is a board certified Pathologists’ Assistant, specializing in surgical and gross pathology. He currently works as a Pathologists’ Assistant at the University of Chicago Medical Center. His job involves the macroscopic examination, dissection and tissue submission of surgical specimens, ranging from biopsies to multi-organ resections. Cory has a special interest in head and neck pathology, as well as bone and soft tissue pathology. Cory can be followed on twitter at @iplaywithorgans.

I Had a Blast

Hi again everyone!

Welcome back. Last month I talked about a colleague of mine, a fellow student who’s pursuing a career in pathology. The month before that I wrote a bit about Just Culture and how those of us in laboratory medicine ought to act as leaders for patient advocacy—especially when it comes to putting the needs of patients first. And in the spirit of progressing career timelines and fortuitous transitions, this month I want to talk about a place where Just Culture is tangible, where “patient come first” is a mission statement, and where I just spent the last month rotating in their Department of Laboratory Medicine and Pathology: The Mayo Clinic.

Image 1. Commemorative statue of the Mayo brothers in a park in front of the main building of the downtown campus at Mayo Clinic in Rochester, MN.

Before I go any further, if you haven’t seen the PBS Ken Burns’ documentary, I highly suggest you do; it’s fantastic. There are also a few excellent books on the hospital’s history and vision here and here. But back to the rotation: I can’t express how lucky I feel having spent time there or convey how much of a privilege it was to see pathology in a uniquely Mayo way. What I can do is try to talk a little bit about my experience and what that translates to regarding a culture of advocacy and collaboration; and I’ll share a case conference I presented on my last day in a topic I find fascinating.

Image 2. Ken Burns presents The Mayo Clinic: Faith, Hope, and Science on PBS, which aired September 2018.

Mission, Vision, and Values

As with any hospital, academic center, clinic, etc., you’re always going to have a driving philosophy that anchors the values of that particular institution. Some of my experiences in larger academic centers tout their strides at the forefront of medicine and translational research, others advertise that they treat the whole person body and spirit. Community hospitals sometimes lean into their integral part of, well, their communities as a center for trust and health. Sometimes institutions have specific populations to cater to or work intensely with industry and boast strong contributions to medical science. At the Mayo Clinic you’d be hard pressed to miss the message (in various forms) that “The Patients Come First”—in fact that line from many years ago comes from Dr. William Mayo delivering a commencement speech at a Rush Medical College graduation. (I was so happy to see so many Chicago-Mayo Clinic connections!)

Image 3. Dr. W. Mayo articulated the concept of patients’ “needs come first” in a graduation speech at Rush Medical College in Chicago on June 15, 1910.

It becomes very obvious that this culture of advocacy permeates into the daily proceedings there. The hospital makes a strong point to celebrate outreach, education, and research; and clinicians are given a cultivated environment in which to flex muscles of compassion for patient outcomes. It makes you a better clinician, and I argue, person. Everyone at this hospital has a voice and a seat at the table. I was continuously encouraged to interact with staff, clinicians, residents, fellows, and patients and contribute what I thought would benefit patient care. A unique perspective as a visiting medical student with previous MLS experience was both noted and celebrated.

Leadership in Pathology

In many of my pieces on this blog, I frequently discuss how we should champion active roles in testing stewardship, policy advocacy, and promoting positive patient outcomes. Granted, when you find yourself in larger, resource-rich, tertiary academic centers you can really push the envelope for progress. But generally, those of us on the ‘scopes operate in this margin between clinical medicine and translational research. Where does our leadership come in? What does it look like? I think it comes in the form of prolific contributions to societal guidelines and interdisciplinary work. Nowhere have I seen this more than my month in Rochester.

So many of their residents contributed abstracts and presentations at this year’s USCAP conference, some winning awards. The academic cycle of producing something great requires strong support from your home institution and that’s exactly what I saw. Not only were folks supported for their trips to conferences per usual, they were celebrated—hallway handshakes, accolades at morning conference, discussions post-meeting, and social media shares. Which, by the way, social media is now a leadership staple. You can’t go far in the present day without utilizing technology both inside and out of your practice. The Pathologist recently celebrated their first #TwitterPathAward for residents like Dr. Tiffany Graham at UAB for contributions to medical education and advocacy in pathology. Mayo clinicians, including residents, consultants, pathologist’s assistants, and more share case studies, educational material, and cutting-edge pathology news in terabytes! I now find myself increasingly active on social media representing pathology and interests within our field.

Image 4. A spring 2015 issue of The Pathologist discussed the increasing presence of pathology in social media and the trends of utilization for medical laboratorians abound.

Side note: I’ve followed a number of these social media pages about cases in pathology for a while, and when I was fortunate enough to be part of ASCP’s Top 40 Under Forty 2017, I connected with lots of awesome laboratorians. Some of which I got to meet this month! Including a fellow blogger on this site, some celebrated path assistants, and a prolific parasite-discussing clinical microbiologist.

Case Conference

So, my presentation was intense! I’ve given plenty of case reports and conference discussions before, but this was an opportunity for me to explore quite a rare case in genetics and connect it with my interests in hematopathology. This was a case of a patient with Li-Fraumeni Syndrome (LFS) who developed therapy-related Acute Myeloid Leukemia. It’s not a current case and has since been signed-out and closed, but I’ll only be talking about the pathologic entities involved.

Image 5. Remember that power of social media I mentioned earlier? Well, what better way to share information for other medical students interested in pathology and interested in visiting Mayo Clinic! Having my presentation grab an honorable mention amidst their productive and busy residents was great! #path2path #hemepath #lablogatory

Essentially, this patient was found to have Li-Fraumeni after the second manifestation of an acute sarcoma—the first being osteosarcoma in her teenage years and the second breast cancer in her 30s. Both cancer diagnoses were treated accordingly, and this patient was going through routine work-up for anemia before being referred to the Mayo Clinic. By the time the patient reached there, the clinical investigation included a battery of testing for causes of anemia—all within normal limits—so a bone marrow examination was performed which revealed a significant, though not acute (<20% blasts), myelodysplastic process. A follow-up in-house bone marrow collection revealed hypercellular marrow, now in acute myeloid proliferation, with abnormal myeloid cell maturation and very complex cytogenetics. She had a very complex karyotype and several detectable mutations which were consistent with the WHO’s classification and description of therapy-related myeloid neoplasm as a sequale to the treatments she received for her prior cancers. In the setting of a patient with LFS, it is almost impossible to avoid malignancy. The following slides are a (very abridged) summary taken from my presentation of this patient’s case:

Figure 1. Official LFS and AML discussion. As mentioned, this is the case of a patient with a history of osteosarcoma and breast carcinoma, both treated, now presenting status-post initial work-up for evaluating possible causes for anemia. Ultimately, when reaching a bone marrow examination, certain myelodysplastic features were discovered, referring this case for close investigation and expanding the differential to include various hematologic malignancies.
Figure 2. This bone marrow biopsy was evaluated at an outside institution and was reported to this patient’s case at Mayo Clinic. Note the presence of myeloid lineage blasts cells in the peripheral blood (PB) and bone marrow (BM) evaluations, however, at less than 20% this would not immediately indicate any acute myeloid crisis. There is a definitive left-shift in maturity with myeloid dysplasia.
Figure 3. This bone marrow evaluation was done about a month after the previous reported one. Note the significant increase in myeloid blasts present in both peripheral and bone marrow specimens. This time, there was significant dysplasia noted in multiple lineages as well as particular changes in granulocytic lines including left-shift and pseudo Pelger-Huet cells present. This diagnosis was upgraded from myeloid dysplasia to acute myeloid leukemia in the setting of myelodysplasia. The blast count has now crossed the 20% threshold and there are marked changes to morphology in several cell lines. Hypercellularity and cytogenetic testing were also highly contributory in this diagnosis. Not included in this slide but CD34+ cells that previously expressed CD15, CD33, and CD38 were now negative for those three markers. This indicates decrease in maturity and a poorer prognostic and clinical assessment of this malignancy.
Figure 4. A peripheral blood smear at the time of the second bone marrow specimen. In almost every field photographed, there were myeloid blast cells present. No Auer rods were seen, but many blasts had granules. There was left shift, and some immature granulocytes were present. Erythroid immaturity was demonstrated with morphology and circulating nucleated RBCs. Abnormalities in granulocytic lineages were present with hypogranular neutrophils and pseudo Pelger-Huet morphology.
Figure 5. At nearly any age, this bone marrow needle core biopsy on H&E stain would qualify as hypercellular. At low to medium power this is clearly evident. At higher powers, note the presence of predominantly immature granulocytes (with very few, if any, mature PMNs) as well as numerous blasts—on H&E blasts appear differently, but appreciate the increased number of cells with active nuclei, condensing chromatin, and prominent nucleoli.
Figure 6. Back to traditional hematology staining, you can still appreciate this bone marrow aspirate’s hypercellularity. There is a labeled megakaryocyte (which appears slightly abnormal) to scale against the numerous, immature and left-shifted granulocytes which overrun the fields. Myeloid blasts are seen in high numbers, with granules and prominent nucleoli. Increased levels of mitotic activity, abundant (and some abnormal) myeloid precursors, and a highly proliferative picture is appreciated.
Figure 7. Li-Fraumeni Syndrome (LFS) is a rare genetic predisposition to soft-tissue sarcomas. It is a germline mutation of either TP53 or CHECK2, more often the former. The mutation usually has an autosomal dominant inheritance pattern and has very high penetrance, more so in females (possibly due to the fact that the most common presentation of tumor formation in LFS is breast cancer). Note that this patient had a clinical history significant for both breast carcinoma and osteosarcoma which were treated with chemotherapy and radiation.
Figure 8a. Patients with LFS often have a germline mutation in p53, a very significant tumor suppressor gene, which is implicated in a wide host of cellular functions. Located on the short arm of Chromosome 17, when mutated this gene affects a myriad of pathways including cell senescence, growth cycle response, proliferation, DNA damage repair from mutations, epigenetic, or exogenous causes, and programmed cell death. If this downstream protection against severe DNA compromise is lost, this becomes a highly pre-cancerous environment for Knudsen’s “second hit” to negatively affect cells and ultimately lead to a vast array of malignancies.
Figure 8b. I mean just look! P53 is a serious player in cell survival and DNA damage recovery. It is the archetype example of a tumor suppressor gene and is implicated in an ever-growing number of cell survival and growth cycle pathways—of course a loss of p53 function would set the stage for high-risk.
Figure 9a. The World Health Organization (WHO) and its updated guidelines for diagnosing and addressing hematologic malignancies now includes a lot of new data regarding the molecular biology of cancer. Its applications to diagnostics in hematopathology are growing daily. In these guidelines, the WHO classify AML into seven general categories. For reasons relating to her clinical history of cancers and treatment, as well as the timeline she presented with, t-MN or therapy-related myeloid neoplasm would be an appropriate diagnosis.
Figure 9b. The American Society of Hematology (ASH) and the College of American Pathologists (CAP) co-wrote guidelines for the diagnosis of AML and published a number of recommendations in The Hematologist in 2017-2018. Essentially, proper laboratory test utilization and incorporation with significant clinical history is crucial. Staying organized and operating within WHO guidelines for hematologic malignancy diagnosis is just as important. The ASH/CAP guidelines tell diagnosticians to think about several key questions when approaching AML which further underscores the values of consistency, efficiency, and appropriate utilization.
Figure 10a. The reason for establishing a diagnosis of therapy-related AML is a significant one. The use of Topoisomerase II inhibitors, alkylating agents, antimetabolites, and radiation therapy all affect the genetic components relating to this particular leukemia. To correlate further, the patient had a 5q deletion, a complex karyotype, a history of receiving all treatments related to this entity, and a presentation of myelodysplasia which rapidly progressed to AML.
Figure 10b. LFS can cause leukemia on its own, AML can present as a hematologic malignancy on its own too; but this patient’s clinical history and treatment history lean the diagnosis away from de novo cancer to a myeloid process in response to a latent treatment effect.

Why All of This Matters

There are two main reasons why all of this is important enough to discuss in a case conference. First, as clinicians from the bench to the bedside we should all strive to talk through the toughest diagnoses and share with each other what best practices, lessons, and goals we can reach together. In the setting of Li-Fraumeni Syndrome it becomes critical to evaluate new onset (especially myeloid) neoplasms. TP53 mutations are associated with the lowest survival rates in acute myeloid leukemia, which has its own diagnostic and prognostic classifications set forth by the World Health Organization. Furthermore, understanding appropriate patient history, clinical information, and what appropriate lab investigation means is crucial. It not only keeps the needs and interests of the patient first, but also translates to the proper utilization of resources for the best results in the best timelines. Potential future implications of concurrent ongoing work in hematopathology and molecular genetics may yield therapeutic and diagnostic benefits we are not yet aware of—we must constantly include updates as we practice.

Second, this was an opportunity to share insights into the diagnosis and discussion of AML that came from my clinical experiences before rotating there. I previously mentioned the demonstrated value of including clinical viewpoints for the benefit of patient care outcomes, so appropriately I incorporated these topics into this case conference and included the following points to consider:

  • Hematologic premetastatic niches

When I was in graduate school at Rush University in Chicago, I did some research in hematopoietic responses to various therapies in the context of proliferation and understanding mobilization for transplant and engraftment. In this work, I became familiar with the concept of a reactive stroma and a “pre-metastatic niche.” There are small microenvironments in which hematopoietic, mesenchymal, and endothelial cell lines in the bone marrow thrive and develop which are full of cytokines and cell-cell interactions. My work focused on mobilizing all three lines with a CXCR4 target, but the concept holds true when considering germline and somatic mutability. In effect, those cells with pre-malignant mutations can cluster and affect the environment of other cells maturing in the same setting. The same way invasive cells can break through barriers to metastasize and spread past their in situ conditions, the same mobilizing spread can grow from pre-metastatic clusters. This, again, opens the discussion for treatment targets in future LFS and/or AML patients as molecular pathology expands.

  • Acute Myeloid Leukemia and Myeloid Sarcoma

In a recently published paper in Histopathology, I was part of a team at the UAB hospital’s department of pathology which discussed their experience with patients diagnosed with myeloid sarcomas (MS). The point was to look for correlations with MS to connect the entity with age, sex, location of tumor, AML status, genetics, etc. Ultimately, what became the highest predictor of disease was a complex karyotype, consistent with other concurrent literature. With respect to this patient, what if there was another soft tissue (or other location) sarcoma alongside her myelodysplastic picture. What if she had a low blast count, or hypocellular bone marrow, or necrosis/fibrosis, or had received G-CSF? Would AML with myeloid sarcoma be considered in this diagnostic setting, would myeloid sarcoma be something to worry about in her future or in her clinical history as a misdiagnosis? The take-home message would be to pay close attention to patient clinical history and stay both focused on the current diagnostic work-up but also open enough to avoid pitfalls in diagnostic challenges.

  • Misdiagnosis in clinical settings

In a case report from 2017 I discussed a patient who had bilateral lung nodules several years after being treated for breast carcinoma. It was initially thought to be relapse but was later correctly diagnosed as de novo peripheral T-cell lymphoma (PTCL). This could have very well been the same clinical scenario, with a different cell lineage. The lesson gleaned here is the same as those ASH/CAP guidelines: stay organized, consistent, and purposeful with your testing and investigation. What came down to a few immunohistochemical markers in this PTCL case could make all the difference in another case. Missing the clinical history and specific genetic mutations present in this LFS/AML patient could have led to a diagnosis of a myelodysplasia related AML instead of a therapy-related one, especially in the setting of such a severe germline pre-disposition.

  • Future plans for this patient

I thought it was ultimately important to discuss the patient’s future plans with the audience. In pathology we often sign-off after we sign-out. So, in order to make sure we emphasize the patient’s best interests moving forward from a poor prognostic diagnosis, we discussed her enrollment in a trial aimed at improving bone marrow donor matching based on HLA and KIR combination typing. This a relatively new and promising concept in the literature which I hold high hopes for.

If anything, this was something I learned last month: in order for you to call the quality of care the highest possible, you have to uphold many standards, both clinical and non-clinical. Clinically we all have to share with each other the latest and greatest in modern literature and advances in interdisciplinary or translational research. Aside from this, however, we have to keep each other human and connected to our patients. I never like to hear the stereotypes in pathology that place us in lab medicine miles away from patient care; instead, we do things every day that impact our patients’ lives greatly. And when we keep ourselves connected to that fact, like the philosophy at the Mayo Clinic, then we can boast our quality of care—from small community hospital to academic trauma center. Because its not the size of the lens on the scope, it’s the vast scope of impact we look through in a lens of compassion.

There you have it. That’s my month at Mayo and a case conference in a nutshell. It was a fantastic experience and I have to say it—I had a blast!

Thanks for reading, I’ll see you next time!

And have a Happy Lab Week 2019!

–Constantine E. Kanakis MSc, MLS (ASCP)CM graduated from Loyola University Chicago with a BS in Molecular Biology and Bioethics and then Rush University with an MS in Medical Laboratory Science. He is currently a medical student actively involved in public health and laboratory medicine, conducting clinicals at Bronx-Care Hospital Center in New York City.

Gastric Cancer: A Multidisciplinary Approach

Maryam Zenali1*, Dmitriy Akselrod2, Eric Ganguly3, Eswar Tipirneni4 and Christopher J. Anker5*

1 Department of Pathology, 2 Department of Radiology, 3 Division of Gastroenterology, and 5 Division of Radiation Oncology, The University of Vermont Medical Center (UVMMC), Burlington, VT and 4 Department of Hematology Oncology, Central Vermont Medical Center (CVMC), The University Of Vermont Health Network, Adult Primary Care, Berlin, VT

*corresponding authors

A 57 year old woman with a personal and family history of breast cancer presented with early satiety and dysphagia for 5 months. Her abdominal computed tomography (CT) scan (Image 1 A) showed marked thickening of an apparently featureless gastric wall (A, blue arrows indicating the mucosal [rightward pointing] and serosal [leftward pointing] aspects of the gastric wall). Prominent gastrohepatic lymph nodes were noted as well. Her fluoroscopic upper GI study (Image1 B), following administration of barium and effervescent crystals (a double contrast effect to allow for mucosal evaluation), showed thickened rugal folds (B red arrow) and pooling of barium within an antral ulcer (B blue arrow). A subsequent CT scan (Image 1 C) after administration of intravenous and enteric contrast, confirmed marked diffuse gastric wall thickening (C blue arrows again indicating the mucosal [rightward pointing] and serosal [leftward pointing] aspects of the gastric wall) (Image 1, composite radiographs A-C).

The gastric body distended poorly with insufflation and demonstrated thickened, erythematous, edematous folds with erosions (Image 2, endoscopy image). On endoscopic ultrasound, the total thickness of the stomach was 12 mm with expanded wall layers in the proximal stomach to the antrum and a thickness of 3.5 mm in spared areas. Biopsies were obtained; the corresponding H&E and keratin stains are provided (Image 3, composite photomicrographs A-B).

Image 1. Composite radiographs.
Image 2. Endoscopy image.
Image 3. Composite photomicrographs.

Based on the original radiographic imaging that led to the biopsy, what are the differential diagnoses?