Surgical Pathology Case Study: A 64 Year Old Man with History of Loose Stools and Abdominal Pain

Case History

A 64 year old male presented with a one year history of loose stools, lower abdominal crampy/gassy pain that improved with defection, and an unclear history of melena. A colonoscopy revealed a circumferential, villous, carpet-like lesion extending from 15 cm to the anal verge, with biopsies demonstrating fragments of a villous adenoma. A follow-up CT scan was negative for metastatic disease. The decision was then made to proceed with a low anterior resection with hand-sewn colo-anal anastomosis and diverting loop ileostomy.

Diagnosis

Upon opening the rectum, a 13.8 cm long circumferential, carpet-like lesion is identified, extending to the distal margin (Image 1). Sectioning demonstrated a lesion with a maximum thickness of 1.0 cm, which grossly appears to be confined to the mucosa. Due to the prior biopsy history of a villous adenoma, the entire lesion was completely submitted. This required 116 blocks to be submitted, which were then mapped out to show where each block would have been taken from (Image 2). Although there were many foci of intramucosal carcinoma present, clear cut submucosal invasion was not identified, and the specimen was signed out as a villous adenoma (Image 3).

Image 1. Opened rectum demonstrating the 13.8 cm-long carpet-like lesion.
Image 2. Mapping the lesion to show from where each block is taken.
Image 3. Photomicrograph showing the transition from normal mucosa (black arrow) to villous adenomatous tissue (red arrow).

Discussion

Polyps are an abnormal tissue growth that is a common occurrence within the colon, although they can also be found throughout the small intestine, stomach and esophagus. Polyps can be further classified as being neoplastic or non-neoplastic based on the histological pattern of the cells. The most common types of neoplastic polyps found within the GI tract are colonic adenomas, which are benign polyps that serve as precursors to the majority of colorectal cancers. Nearly half of adults in the Western world will develop adenomas by the age of 50, and there is no gender predilection. It is because of this that it is recommended that all adults get a colonoscopy by the age of 50 (even earlier when there is a family history of developing colorectal cancer).

Most polyps are small, measuring 0.5 cm or less, but can grow to be over 10 cm in size (as seen in this case). When a colonoscopy is performed, these polyps can appear as sessile, meaning flat, or pedunculated, meaning on a stalk. Due to the abnormal epithelial growth of the mucosa, the surface of an adenoma can have a velvety appearance, resembling that of a raspberry. Most patients will not demonstrate any symptoms from their polyps, with the exception of occult bleeding and anemia which are associated with larger polyps.

Dysplasia, which literally means “disordered growth”, occurs when the individual cells lose their uniformity and architecture, often resulting in cells with a hyperchromatic nuclei and a high nuclear to cytoplasmic ratio. The presence of dysplasia contained within the epithelium of a polyp is what classifies the polyp as an adenoma (Image 4). Based on their epithelial growth pattern, adenomas can be classified as either tubular adenomas or villous adenomas. Tubular adenomas tend to be smaller polyps, with a smoother surface and rounded glands on histologic examination. Villous adenomas, in contrast, tend to be larger polyps with long, slender villi noted on histology (Image 5). If an adenoma contains a mixture of tubular and villous elements, they are classified as tubulovillous adenomas. When a dysplastic cell is no longer contained within the epithelium, and instead breaches the basement membrane which separates the epithelium from the underlying tissue, it is termed invasive.

Image 4. Photomicrograph of the villous adenoma, demonstrating the dysplasia that is confined to the mucosa and not extending to the deeper tissue.
Image 5. Photomicrograph of the long, slender villi that are commonly seen in villous adenomas.

What makes this case so interesting is that there is a direct correlation between the size of an adenoma, and the risk of developing colorectal cancer. This is not true with most other cancers, however, as size plays no part in determining whether the tumor is cancerous or not. With colon polyps, the larger the polyp, the greater the chance of developing invasive carcinoma (i.e. cancer). This is why screening colonoscopies are so important. Studies have shown that regular colonoscopies, combined with the removal of the polyps found on the exam, reduce the incidence of colorectal cancer. Why this case is so interesting is that you could assume based on the size of this polypoid lesion, you would find some invasive component. However, after reviewing 116 blocks, not a single focus of invasion could be identified.

It should be stated that although there is a correlation between an adenomas size and the risk of developing cancer, the majority of adenomas will not progress to cancer, and in fact, there are no tools currently available that help to determine why one patient’s adenoma will progress to cancer, while another patient’s adenoma will not.

References

  1. Association of Directors of Anatomic and Surgical Pathology, adapted with permission by the American Cancer Society. Understanding Your Pathology Report: Colon Polyps (Sessile or Traditional Serrated Adenomas). cancer.org. https://www.cancer.org/treatment/understanding-your-diagnosis/tests/understanding-your-pathology-report/colon-pathology/colon-polyps-sessile-or-traditional-serrated-adenomas.html. Accessed February 14, 2019.
  2. Colon Polyps. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/colon-polyps/symptoms-causes/syc-20352875. Accessed February 14, 2019.
  3. Turner JR. Polyps. In: Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran Pathologic Basis of Disease, 8th edition. Philadelphia, PA: Elsevier, Inc; 2010: 815-820

-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.


Hematopathology Case Study: A 33 Year Old Man with a Mass Behind the Ear

Case History

A 33 year old man of Japanese ethnicity presents with a 2 month history of a mass behind the right ear. Examination reveals a non-tender local with no other local or generalized adenopathy or hepatosplenomegaly. Laboratory investigations reveal an elevated ESR, serum IgE and peripheral blood eosinophilia. The lesion is excised.

Biopsy Findings

H&E stained sections demonstrate a follicular hyperplasia. The germinal centers demonstrate polarity and tingible body macrophages (A). Focally, follicular centers reveal eosinophilic microabscesses (B, C). Immunohistochemical analysis with an IgE stain reveals deposition in germinal centers (D). A diagnosis of Kimura disease is rendered.

Discussion

Kimura disease, also known as eosinophilic lymphoid follicular hyperplasia is a rare, chronic inflammatory disorder of unknown etiology. While an infectious etiology has been suggested, no pathogen has been identified to be causal, to date. Historically, Kimura disease was considered to be the same as Angiolymphoid Hyperplasia with Eosinophilia (ALHE); however, these entities are not the same.

Generally occurring in Asian males, Kimura disease is most common in the 3rd decade of life and in a head/neck site. It presents as painless, slow-growing adenopathy. An association with nephrotic syndrome has been reported. Peripheral blood eosinophilia, elevated ESR, and serum IgE are common findings. Histologically, nodes reveal hyperplastic follicles with well-formed germinal centers and mantle zones with deposition of IgE and eosinophilic microabscesses, as seen in this case. Perinodal soft tissue may be involved. Necrosis may be present, but is not extensive. Cytologically, FNA material may reveal polymorphous cell population with many eosinophils.

Prognosis is indolent; however, most cases recur after excision and radiation therapy usually yields best outcome.

References:

  1. Zhou P. et al. Kimura disease. Dermatol Online J. 2017 Oct 15;23(10).
  2. García Carretero R et al. Eosinophilia and multiple lymphadenopathy: Kimura disease, a rare, but benign condition. BMJ Case Rep. 2016 Aug 31;2016. pii: bcr2015214211. doi: 10.1136/bcr-2015-214211.
  3. Sun QF et al. Kimura disease: review of the literature. Intern Med J 2008;38:668–72.  

Kamran M. Mirza, MD, PhD, MLS(ASCP)CM is an Assistant Professor of Pathology and Medical Education at Loyola University Health System. A past top 5 honoree in ASCP’s Forty Under 40, Dr. Mirza was named to The Pathologist’s Power List of 2018. Follow him on twitter @kmirza

Just Culture: Growing Trend or Lab Requisition?

Hello again everyone!

Last month, I discussed some really interesting topics at the intersection between psychiatry and pathology—two fields that aren’t exactly the closest; more so “diverged” in the hospital milieu as if in a poem by Robert Frost. This month I’d like to bring the conversation back to a topic I’ve addressed before: improving multidisciplinary medicine and creating a Just Culture in medicine.

Not exactly culture with a swab or agar dish, a Just Culture is an all-encompassing term for system-based thinking and process improvement not at the expense of individuals. In a post I made last July, the topic of high reliability organizations (or HROs) is one that addresses communication and accountability in high stakes environments—like healthcare!

Just Culture isn’t a stranger to lab medicine. The American Society of Clinical Laboratory Science (ASCLS) published a position paper in 2015 utilizing this trending healthcare buzzword. On the subject of patient safety, ASCLS believes “Medical Laboratory Professionals must adopt a ‘fair and just culture’ philosophy, recognizing that humans make errors, and understanding the science of safety and error prevention.” (Source: ASCLS 2015, https://www.ascls.org/position-papers/185-patient-safety-clinical-laboratory-science) We all know how we maintain patient safety in the lab, right? We do that through quality control, QA measures, competencies (both internal and from accrediting bodies like CAP), and continuing education. Raise your hand if your lab is getting inspected, just finished getting inspected, will be inspected soon, or if you’ve recently done competency/proficiency testing yourself, CE courses for credentialing, or are reading this blog right now! We’re all “continuing” our education in health care ad infinitum because that’s how it works—we keep learning, adjusting, and ensuring best practices concurrent with the latest knowledge. And, instead of punishing lab professionals when we make errors, we try to be transparent so that each error is a learning opportunity moving forward.

Image 1. I’d panic too if my lab was being inspected by 007. What, you wouldn’t?

I’m currently in my OB/GYN rotation at Bronx-Care and during the most recent Grand Rounds we had someone talk about “Just Culture”—a sort of continuation on the themes of the same lecture series that inspired my article on HROs. Essentially, the theme is that disciplining employees for violating rules or causing error(s) in their work is less effective than counseling, educating, and system-oriented and best-practice-informed care. In this talk, we watched a short video (embedded below) which walked us through approaching faults or errors in medicine in a way that empowers and educates. A story from MedStar Health, a Maryland-based health system, demonstrates how systems-based thinking can be the best way to solve problems in healthcare.

Video 1. “Annie’s Story” has become a widespread example of Just Culture for nearly twenty years. Being serious about high reliability and just culture means adopting a system’s approach to analyzing near misses and harm events—shame and discipline are becoming antiques. Learn more about Quality and Patient Safety (http://ow.ly/M1aZk) and Human Factors Engineering in Healthcare (http://MedicalHumanFactors.net)

Annie, a nurse in the MedStar Hospital system, is the spotlight story in this video. She came across an error message on a glucometer after checking someone who was acutely symptomatic. She double checked it and made clinical decisions, with her providing team, to give insulin. This sent the patient into a hypoglycemic event which required ICU support. In the story, she was actually suspended and reprimanded for her “neglect”—other nurses made the same error just days later. This prompted some action, inciting nursing managers and other administrators to investigate further, ultimately involving the biomedical engineers from the company to weigh in on this systemic fault in glucose POCT. Annie returned to work, and the problem was recognized as not user-error, but system error; she went on to talk about how she felt unsure of her clinical competency after being reprimanded. Imagine if you accidentally reported the presence of blast cells in a manual differential in a pediatric CBC while you were alone on a night shift only to find out from the manager on days that you made a pretty big mistake with clinical implications. Then imagine you were suspended for a few weeks instead of simply asked to explain and identify opportunities to increase your knowledge. Pretty harsh, right? I’m glad the MLS who did that didn’t lose his job and only had to do a few more competency trainings…yep.

Fine. It was me. I mentioned mistakes in my discussion on HROs and discussed that particular mistake in part of a podcast series called EA Shorts with a clinical colleague of mine. Everyone makes mistakes, especially in training, and that’s okay! It’s how we deal with them that matters.

Image 2 (a, b). Take a look at that glucometer. Would you have caught the error? Did you catch the “LO” value in the background vs. the out-of-range foreground prompt? Or was the screen prompt as distracting for you as it was for Annie? Who was responsible for this error: nurse, lab, or engineer?

Anyone else notice a stark absence of professional laboratory input in the video? I assume many of you sharp-sighted lab automation veterans didn’t miss the glaring “LO” behind the dialogue box on the glucometer. And, to me, that begs the question: was there any lab input on this instrument, its training, or its users? Nurse Annie made a mistake—but she’s not alone, according to a Joint Commission study from November last year, close to 11% of users make mistakes when prompted with error messages compared to 0% of users misinterpreting normal values on screens of a particular model of glucometer. And that’s just one type of instrument. Imagine 1 in 10 nurses, medical assistants, or patients misinterpreting their glucose readings. (Source: The Joint Commission Journal on Quality and Patient Safety 2018; 44:683–694 Reducing Treatment Errors Through Point-of-Care Glucometer Configuration) This should also be a good opportunity to remind us all of CLIA subpart M, the law that outlines who can accredit, use, and report point-of-care results. Herein lies another problem, stated well by the American Association for Clinical Chemistry (AACC) in 2016, “… another criteria for defining POCT—and possibly the most satisfactory definition from a regulatory perspective—is who performs the test. If laboratory personnel perform a test, then this test typically falls under the laboratory license, certificate, and accreditation, even if it is performed outside of the physical laboratory space, and regardless of whether the test is waived or nonwaived. On the other hand, waived or nonwaived laboratory tests performed by non-laboratory personnel are nearly always subject to a different set of regulatory and accreditation standards, and these can neatly be grouped under the POCT umbrella,” and that can mean trouble when we’re all trying to be on the same clinical page.

In previous posts, I’ve mentioned the excellent knowledge contained within the Lab Management University (LMU) program. One of the modules I went through discussed this topic exactly: Empowerment as a Function of Leadership and Peak Performance. In short, if we want to be good leaders in the lab, we have to set expectations for positive patient outcomes, including safety. Good leadership should empower their staff with education, support, and resources. Poor management can create toxic environments with staff that can be prone to mistakes. If we can be dynamic leaders, who adapt to ever-improving best practices and respond with understanding and compassion to mistakes, then our colleagues become just as reliable as your favorite analyzer during that CAP inspection I mentioned.

Image 3. LMU class module for promoting Just Culture and inciting positive behavior in your department.

I often get clinician input about how the processes between the bedside and the lab can be improved. Often, they include comments about the need to share relevant clinical data for improving diagnostic reporting or improving a process between specimen collection and processing. But what often gets left out is the human element: the scientist behind the microscope, the manager behind the protocol, and the pathologist behind the official sign out report. Let’s continue to incorporate all of the feedback our colleagues provide while maintaining a safe and empowered culture for ourselves, our staff, and our patients.

What do you think? How does your lab, hospital, clinic, etc. address POCT safety or patient safety at large? Do you operate within a Just Culture? Share and comment!

Thanks and see you next time!

–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.

Hematopathology Case Study: A 60 Year Old Man with Recurrent Bronchitis

Case History

60 year old man with recurrent bronchitis and extensive smoking history underwent CT scan. The CT scan showed an incidental finding of a 2.2 x 1.4 cm anterior mediastinal mass.

Excision

H&E4x
H&E 4x
H&E10x
H&E 10x
H&E20x
H&E 20x
cytokeratin cocktail
Cytokeratin cocktail
CD3
CD3
CD20
CD20
TdT
TdT

Diagnosis

The tissue shows nodules of epithelial cells in a lymphocyte-rich background. The epithelial cells have round to somewhat spindle shaped nuclei, vesicular chromatin and small mostly inconspicuous nucleoli. There is no high grade cytologic atypia, mitotic figures or necrosis seen. The nodules contain very few interspersed lymphocytes, but are surrounded by abundant lymphocytes which are small and mature appearing. A cytokeratin cocktail highlights the epithelial nodules and shows an absence of epithelial cells in the lymphocyte-rich areas. CD20 highlights stromal B-lymphocytes around the epithelial nodules which are arranged in follicles. CD3 highlights stromal T-lymphocytes, which surround the B-cell follicles and the epithelial nodules. TdT highlights only a very small subset of immature T-cells which are found scattered around the rim of the epithelial cell nodules. Overall, the findings are consistent with a micronodular thymoma with lymphoid stroma.

Discussion

The differential diagnosis for an anterior mediastinal mass includes thymoma, lymphoma, germ cell tumors, neurogenic tumors and benign cysts among other less common entities. Patients usually present with cough, chest pain, fever/chills or dyspnea and localizing symptoms are generally secondary to local tumor invasion. Typically, CT scans are the best modality to evaluate the mediastinum. Thymomas are the most common primary neoplasm of the anterior mediastinum, but are less than 1% of all adult malignancies. Patients are generally over 40 years old and between 30-50% of patients with a thymoma have myasthenia gravis, which occurs more frequently in women.1

The WHO has classified thymomas into 5 categories based on the morphology of the neoplastic epithelial cells along with the lymphocyte to epithelial cell ratio. Type A thymomas are composed of bland spindle/oval tumor cells with few or no admixed immature lymphocytes. Type B1 thymoma resembles normal thymus and has scattered epithelial cells in a dense background of immature T-cells. Type B2 thymoma is composed of epithelial cells in small clusters with a lymphocyte-rich background. Type B3 thymoma is primarily composed of mild to moderately atypical epithelial tumor cells in a solid growth pattern with few intermingled immature T-cells. Type AB thymomas are composed of lymphocyte-poor spindle cell (Type A) components as well as lymphocyte-rich (Type B) components.2

Micronodular thymoma with lymphoid stroma (MTWLS) is a rare type of thymoma and accounts for only 1% of all cases. Patients tend to be asymptomatic and the finding is usually incidental. The tumor tends to be well circumscribed and encapsulated with a tan cut surface. The histopathology is characterized by solid nests or nodules of epithelial tumor cells in a background of abundant lymphoid stroma. The tumor cells are bland spindle or oval cells without significant atypia or mitotic activity. The epithelial tumor cells are positive for pancytokeratins. The lymphoid stroma typically lacks keratin positive cells and consists of predominantly CD20 positive mature B-cells in follicles with admixed CD3 positive and TdT negative mature T-cells. There is typically a population of rare TdT positive immature T-cells that surrounds the epithelial nodules, as seen in this case. 2

Due to the rarity of MTWLS with only 74 cases reported since the first case described in 1999, there is limited data on its pathophysiology and prognosis. However, most cases are diagnosed as stage I/II disease according to the Masaoka-Koga staging criteria, involving only micro or macroscopic invasion into thymic or surrounding fatty tissue without invasion into neighboring organs.  Patients tend to have a very favorable prognosis with most patients alive without recurrence or metastasis many years after diagnosis.3

References

  1. Juanpere S, Cañete N, Ortuño P, Martínez S, Sanchez G, Bernado L. A diagnostic approach to the mediastinal masses. Insights Imaging. 2012;4(1):29-52.
  2. Travis WD, Brambilla E, Burke AP, et al. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart (Revised 4th edition). IARC: Lyon 2015.
  3. Qu L, Xiong Y, Yao Q, Zhang B, Li T. Micronodular thymoma with lymphoid stroma: Two cases, one in a multilocular thymic cyst, and literature review. Thorac Cancer. 2017;8(6):734-740.

Chelsea Marcus, MD is a Hematopathology Fellow at Beth Israel Deaconess Medical Center in Boston, MA. She has a particular interest in High-grade B-Cell lymphomas and the genetic alterations of these lymphomas.

Neuroendocrine Neoplasms of the Pancreas: A Multidisciplinary Approach

Authors: Dr. Maryam Zenali (Department of Pathology), Dr. Eric Ganguly (Department of Gastroenterology), and Dr. Christopher J. Anker (Division of Radiation Oncology), University of Vermont Medical Centerr

Case 1: Patient 1 is a 75 year old man with a history of gastroesophageal reflux disease (treated with a proton-pump inhibitor) who had an episode of diaphoresis and altered mental status at 3:30 am. He was found to have a glucose of 20 when rescue arrived. He was brought to the ED and symptoms resolved after glucose administration. Work-up showed fasting C-peptide of 3.5 (normal range: 1.1-4.4 ng/mL) ruling out excess insulin use; proinsulin was elevated at 300 (normal range: 3-20 pmol/L). Serum chromogranin A was noted to be mildly elevated. He had a CT scan of the abdomen that did not show any abnormal enhancement or concerning lesion. Endoscopic ultrasound (EUS) imaging demonstrated a slightly hypoechoic mass in the pancreatic head with a hyperechoic halo margin. The mass was adjacent to, although not invading, the portal vein. The remainder of the pancreatic head had a normal echotexture (figure 1A). Fine needle aspiration and biopsy of the lesion were performed; microscopic images are provided (figures 1B and 1C).

Histology: A relatively monotonous, well-differentiated tumor with regular, round salt-and-pepper chromatin and eosinophilic cytoplasm. There were only rare apoptotic cells and no mitosis. 1% of tumor nuclei were immunoreactive with MIB-1 (Ki67 K2 Leica). Tumors cells were diffusely and strongly positive for synaptophysin (27G12, Leica), chromogranin (LK2H10, Ventana) and keratin (AE1-AE3, Biocare) but negative for makers such as TTF1, CK7, Beta-catenin and GATA-3.

What is most likely the diagnosis?

Albumin Values in Transgender Men and Women

This month our study results were published in a special edition of Clinical Chemistry describing how laboratory values in transgender men and women when taking hormone therapy. While retrospective, we hope that this information will help improve transgender medicine.

There were many interesting results found in the study and I hope to describe bits of them in greater detail each month.

We wondered what we might find if we took a broad, unbiased approach comparing all laboratory parameters commonly measured by physicians. Just because there are no sex-specific differences in analytes, changes could still occur secondary to exogenous hormone use.

Albumin, which is the principle protein in our blood, was found to be decreased in transgender women after taking at least 6 months of estradiol therapy (p<0.0001)1. This was unexpected, because one reference range for albumin is used for cisgender males and females.

Frequently, changes in lab values move in opposite directions for transgender patients taking estradiol vs. testosterone (ex. hemoglobin goes up with testosterone and down with estradiol). We wondered if a similar opposite change might occur in albumin for transgender men taking testosterone. However, there was no change in albumin levels from baseline for transgender men.

The cause of decreased albumin was not readily available, but several factors could be influential. Albumin levels reflect the long term nutritional status of a patient as it has a long half life for turnover (t½= 3-4 weeks). Thus, the change in albumin could reflect a dietary change in transgender women. However, in the chart review there was nothing to suggest a substantial change in diet. While several of the patients would go on diets and lose weight, the weight loss was (unfortunately) often short lived (< 1 year). Looking towards a more objective reflection of dietary changes, the body mass index was nearly the same for transgender women pre-hormone therapy vs. while on hormone therapy (BMI: 27 vs 29, p>0.05).

Some studies have shown an increased prevalence of disordered eating behaviors among transgender individuals2, which could affect overall nutritional status as reflected in albumin. However, this should be controlled for by the control group, which is just transgender patients who haven’t taken hormones previously. 

Another consideration is that body composition changes in transgender patients such that transgender women lose lean mass and have an increase in body fat percent3. Although this could affect the metabolic profile (which it didn’t in our study), changes in fat percent don’t explain altered albumin levels.

Albumin levels are also low in patients with chronic liver disease, but this would be inconsistent with the patients’ medical history or other lab results. Frank nephrotic syndrome is unlikely as there were no reports of this disease within our population, but we did not have data on urinalysis, so we can’t say for certain.

One study did show that males (TW baseline equivalent) have higher albumin than females at younger ages (<60 y.o.) that equilibrates in later decades4. This sex-specific difference shows how estradiol decreases albumin to cisgender female levels. However, the reverse effect (increased albumin) does not occur with testosterone in transgender males. This demonstrates how sex-specific reference intervals cannot be simply reversed for transgender patients.

In a normal set of outpatients in the UK, oral contraception use (which includes estradiol) in women decreased their albumin levels by 0.2 g/dL, which is a smaller magnitude than found in our study, but supports a hormonal basis for sex-specific differences in albumin4.

Although the decrease in albumin for our cohort was not clinically significant (did not pass lower limit of normal albumin reference interval), it would be important to monitor albumin levels in older or elderly transgender females on hormone therapy. Elderly patients are at increased risk of hypoalbuminemia, especially when hospitalized5.

Summary:

  1. Albumin is decreased in transgender women taking estradiol therapy.
  2. Albumin levels do not fall below normal ranges.
  3. This could be more important in older or elderly transgender patients who are already at risk of hypoalbuminemia.

References

  1. SoRelle JA, Jiao R, Gao E et al. Impact of Hormone Therapy on Laboratory Values in Transgender Patients. Clin Chem. 2019; 65(1): 170-179.
  2. Diemer EW, Grant JD, Munn-Chernoff MA et al. Gender Identity, Sexual Orientation, and Eating-Related Pathology in a National Sample of College Students. J Adolesc Health. 2015; 57(2):144-9.
  3. Auer MK, Cecil A, Roepke Y et al. 12-months metabolic changes among gender dysphoric individuals under cross-sex hormone treatment: a targeted metabolomics study. Sci Rep. 2016; 6: 37005.
  4. Weaving G, Batstone GF, Jones RG. Age and sex variation in serum albumin concentration: an observational study. Annals of Clinical Biochemistry 2016, Vol. 53(1) 106–111.
  5. Cabrerizo S, Cuadras D, Gomez-Busto F et al. Serum albumin and health in older people: Review and meta analysis. Maturitas. 2015; 81(1):17-27.

-Jeff SoRelle, MD is a Molecular Genetic Pathology fellow at the University of Texas Southwestern Medical Center in Dallas, TX. His clinical research interests include understanding how the lab intersects with transgender healthcare and advancing quality in molecular diagnostics.

Hematopathology Case Study: A 65 Year Old Male with a Skin Lesion on the Right Shoulder

Case History

A 65 year old Caucasian male presents with a skin lesion on his right shoulder. Physical examination reveals a 3 .0 cm  ×  1.5  cm hyperpigmented plaque with mild hyperkeratosis on his right shoulder and multiple scattered erythematous macules and plaques on the trunk and back Skin biopsy reveals involvement by Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). PET scan reveals no extracutaneous involvement.

The patient undergoes CHOP chemotherapy followed by autologous hematopoietic stem cell transplantation. He is subsequently treated systemically with lanolidomide, venetoclax, and idelalisib due to relapses of disease.

The patient returns to clinic three years later for follow-up. While his original cutaneous lesions are completely resolved, new lesions are noted on his back (representative lesion, Image 1). Hematologic evaluation is remarkable for pancytopenia with hemoglobin 8.7gm/dL, white blood cells 1.4 K/uL, and platelets 39 K/uL. A biopsy of the bone marrow is performed.

Image 1. Skin lesion on back.

Biopsy Findings

Core biopsy
CD56
Aspirate

H&E stained sections demonstrate a normocellular bone marrow with diminished trilineage hematopoiesis and sheets of amphophilic, blastoid cells with irregular borders occupying most of the marrow cells. Immunohistochemistry demonstrates a cellular population with CD56. The aspirate smears show similar findings with numerous clustered blastoid cells (92%) with a monocytoid appearance, often with basophilic vacuolated cytoplasm. There is also a decrease in myeloid and erythroid precursors.

Flow cytometric analysis performed on the bone marrow aspirate reveals a dim CD45 population with expression of CD4, CD56, partial CD7, dim and partial CD5, and CD38. The same population lacks expression of immaturity markers such as CD34, MPO, and TdT. The morphologic and phenotypic findings found in the marrow specimen are diagnostic of extensive involvement of the marrow by BPDCN.

Discussion

BPDCN is a rare and highly aggressive malignancy derived from precursors of plasmacytoid dendritic cells. Its nomenclature has constantly changed over years as the understanding of this entity has been improved. It has been variously known as blastic natural killer cell lymphoma/leukemia, agranular CD4+ natural killer cell leukemia, and CD4+CD56+haematodermic neoplasm. It is currently classified under acute myeloid leukemia and related precursor neoplasms in the most recent WHO classification of tumours of haematopoietic and lymphoid organs.

Limited data exist regarding the incidence of BPDCN; however, it is estimated to account for 0.7% of primary cutaneous skin lymphomas and 0.44% of all hematological malignancies. This hematodermic malignancy predominantly affects elderly male patients with mean age ranging from 60 to 70; however, a few cases have also been reported in childhood and infancy. As demonstrated in our case, the patients typically present with multiple violaceous skin lesions, which may be associate with erythema, hyperpigmentation, purpura, or ulceration. Extracutaneous involvement is reported to occur in the bone marrow, peripheral blood, and lymph nodes.

Diagnosis of BPDCN relies on histological and immunophenotypic findings. Histologically, BPDCN may show a monomorphic infiltrate of medium-sized immature blastoid cells with round nuclei, finely dispersed chromatin, and cytoplasmic vacuoles. They typically display immunophenotypic expression of markers CD4, CD56, CD123, and T-cell leukemia/lymphoma 1 (TCL1) without any lineage-specific markers of T cells or B cells. Chromosomal abnormalities involving 5q, 12p,13q, 6q, 15q, and 9p have been reported. The differential diagnosis entails, but is not limited to, mature T-cell lymphoma, nasal-type NK/T-cell lymphoma, myeloid sarcoma/acute myeloid leukemia and T-cell lymphoblastic lymphoma/leukemia

The clinical course of BPDCN is aggressive, with a median survival of 9 to 16 months. The patients with disease limited to the skin may have a better prognosis, while advanced age and advanced clinical stage are indicators of poor prognosis.  There is currently no consensus on optimal management and treatment because of low incidence of BPDCN; however, most patients are treated with regimens used for other hematopoietic malignancies (i.e. CHOP and hyperCVAD) followed by allogeneic stem cell transplantation for eligible patients. They often respond well to chemotherapy with complete resolution of skin lesions; however, relapse of disease can occur due to resistance to chemotherapeutic agents, which may have happened in our case.

References

  1. Lim MS, Lemmert K, Enjeti A. Blastic plasmacytoid dendritic cell neoplasm (BPDCN): a rare entity. BMJ Case Rep. 2016;2016:bcr2015214093.
  2. Grushchak S, Joy C, Gray A, Opel D, Speiser J, Reserva, Tung R, Smith SE. Novel treatment of blastic plasmactoid dendritic cell neoplasm: a case report. Medicine (Baltimore). 2017 Dec;96(51):e9452.
  3. Dhariwal S, Gupta M. A case of blastic plasmacytoid dendritic cell neoplasm with unusual presentation. Turk J Haematol. 2018 Jul 24. doi: 10.4274/th.2018.0181.
  4. Shi Y, Wang E. Blastic plasmacytoid dendritic cell neoplasm: a clinicopathologic review. Arch Pathol Lab Med. 2014 Apr;138(4):564-9.
  5. Bulbul H, Ozsan N, Hekimgil M, Saydam G, Tobu M. Report on three patients with blastic plasmactoid dendritic cell neoplasm. Turk J Haematol. 2018 Sep;35(3):211-212.
  6. Kerr D 2nd, Sokol L. The advances in therapy of blastic plasmacytoid dendritic cell neoplasm. Expert Opin Investig Drugs. 2018 Sep;27(9):733-739.
  7. Pagano L, Valentini CG, Pulsoi A, Fisogni S, Carluccio P, Mannelli F, et al. Blastic plasmactoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study. Haematologic. 2013 Feb;98(2):239-246.

-Jasmine Saleh, MD MPH is a pathology resident at Loyola University Medical Center with an interest in dermatopathology and hematopathology. Follow Dr. Saleh on Twitter @JasmineSaleh.

-Kamran M. Mirza, MD PhD is an Assistant Professor of Pathology and Medical Director of Molecular Pathology at Loyola University Medical Center. He was a top 5 honoree in ASCP’s Forty Under 40 2017. Follow Dr. Mirza on twitter @kmirza.