8 June 2023: Textbook Updates

We have posted updates of the following topics:

Bladder, ureter & renal pelvis > Glandular neoplasms > Urachal adenocarcinoma
by Rugvedita Parakh, M.D., Maria Tretiakova, M.D., Ph.D.
Topic summary: Adenocarcinoma arising from the epithelium lined tubular structure known as urachus, an embryological derivative of the urogenital sinus and allantois that connects the bladder to the umbilicus; diagnosis of urachal adenocarcinoma is usually established after excluding other mimics. Rare, < 1 case per 1 million of population. Clinical features: hematuria and irritative bladder symptoms with voiding difficulties (hematuria, dysuria, nocturia, frequency, suprapubic pain). Urachal adenocarcinoma is a clinicopathologic diagnosis. Staging is different than bladder carcinoma; local recurrence and metastatic disease are common. Treatment: umbilectomy with partial cystectomy, possibly laparoscopic.

Cervix > Inflammatory / infectious > Lactobacillus
by Hiba Al Dallal, M.B.Ch.B., Ziyan T. Salih, M.D.
Topic summary: Lactobacillus spp. is normal vaginal flora that is commonly seen in cervical Pap smears; they are beneficial because they produce lactic acid, which reduces the vaginal pH and possibly protects from infection by Candida and other pathogens. Lactobacillus is predominant during the second half of the menstrual period (luteal phase). They are blue thick rods usually found on the top of the intermediate squamous cells.They can lyse glycogen rich intermediate cells which may cause cytolysis. Excessive lactobacterial cytolysis can be associated with vaginosis-like symptoms (cytolytic vaginosis) and may cause vulvovaginal itching, burning and discharge. No treatment is needed.

CNS & pituitary tumors > Gliomas, glioneuronal tumors, and neuronal tumors > Neuronal and mixed neuronal-glial tumors > Central neurocytoma
by Daniel D. Child, M.D., Ph.D., Rebecca Yoda, M.D.
Topic summary: Rare, well differentiated, intraventricular neoplasm with neuroepithelial differentiation, typically arising near the foramen of Monro. Microscopically appears as sheets of uniform, small – medium, round cells with fine chromatin stippling (salt and pepper) and occasional perinuclear clearing, interspersed with patches of fibrillary matrix. ~0.1 – 0.5% of all primary brain tumors; mean age at presentation: 20 – 34 years. Most common presenting symptoms are related to increased intracranial pressure that is due to obstructive hydrocephalus. Generally favorable prognosis: 5 year overall survival rate: 96%; 10 year overall survival rate: 82%. Surgical resection is standard of care; when complete resection is not possible, adjuvant radiotherapy improves survival.

Informatics, digital & computational pathology > Laboratory information systems > LIS fundamentals
by Ugochukwu John Jonah, M.B.B.S., Anil Parwani, M.D., Ph.D., M.B.A.
Topic summary: A laboratory information system (LIS) is computer software that processes, stores and manages data from all stages of medical processes and tests: patient check in, order entry, specimen processing, results entry and patient demographics. It reduces the turnaround time of laboratory tests and significantly decreases errors. LIS is only certified to be of functional capacity when it meets the meaningful use program criteria of the 2009 Health Information Technology for Economic and Clinical Health (HITECH) Act; such certified LIS is usually referred to as an electronic health record [EHR] module. Ideal LIS will prevent unauthorized access in order to preserve the confidentiality of health records and ensure that only legitimate users can be granted access to the system.

Oral cavity & oropharynx > Benign epithelial tumors & processes > Verruca vulgaris
by Molly Housley Smith, D.M.D.
Topic summary: Benign epithelial proliferation of squamous mucosa; associated with human papilloma virus (HPV) types 2 and 4. Mostly found on the skin but uncommonly may be seen in the oral cavity; similar to cutaneous lesions both histopathologically and microscopically. M > F; wide age range, although more frequent in younger populations. Asymptomatic, well delineated, often white papule or nodule with a papillary or pebbled surface. Lips, palate, anterior tongue most common but can affect any intraoral location. HPV is thought to gain access to epithelial cells via microabrasion or trauma. Treatment: excision (via surgery, cryosurgery or electrosurgery); spontaneous regression has been reported. Good prognosis; rare recurrence attributed to incomplete removal of lesional tissue.

7 June 2023: Strategic Plan to Substantially Reduce Cancer Deaths

We have revised our strategic plan to substantially reduce cancer deaths at pathologyoutlines.com/ccnstrategicplan.html. Our plan is summarized at natpernick.substack.com/p/our-strategic-plan-to-substantially and below:

This strategic plan, created in February 2021, aims to substantially reduce cancer deaths in the United States from 600,000 projected for 2023 to 100,000 per year. After 50 years of fighting the War on Cancer, we need to “dare greatly” and to determine our desired cancer related goals and how we might attain them, even if many steps are unknown. Thus, our strategic plan differs from “challenge goals” that are based on “applying known interventions broadly and equitably”.

This strategic plan is essentially a management plan to use all of the treatment and public health approaches possible that may impact cancer deaths. It is not sensible to focus on a “silver bullet” or other miracle treatment. Success will likely arise from combinations of an expanding number of modest improvements.

Our specific strategies are:

1. Treatment should target as many individual biologic networks as possible that contribute to the cancer itself, directly or indirectly. In addition, our public policies must optimize all aspects of our healthcare system that affect cancer deaths.
2. Successful treatment will likely require combinations of combinations of therapy, each attacking a different aspect of the malignant process.
3. We should initially focus on aggressive cancers that cause the most cancer deaths.
4. We should reduce cancer deaths that occur shortly after diagnosis.
5. We should incorporate therapeutic strategies that delay cancer deaths.
6. We should focus on reducing age related cancer deaths.
7. We should attempt to enroll every patient in a clinical trial so physicians can learn and improve.
8. We should make our prevention programs more effective.
9. We should develop better screening programs for cancers with high mortality.

The full strategic plan with references is at pathologyoutlines.com/ccnstrategicplan.html.

Our blog version of this essay is at natpernick.substack.com/p/our-strategic-plan-to-substantially.

Email Dr. Pernick your comments to Nat@PathologyOutlines.com.

6 June 2023: Meet the Editor – Farres Obeidin, M.D.

Please introduce yourself.

Hi there! I’m a current attending pathologist at Northwestern University, Feinberg School of Medicine in Chicago. My main area of expertise is bone and soft tissue pathology, but I also sign out other surgical specialties, including head and neck and thoracic. Originally from Georgia, I decided to brave the arctic chill and move up to Northwestern for residency. My bone and soft tissue fellowship was completed at UCLA in 2020, and since then, I’ve moved back because the West Coast was just a little too nice. 🙂

Why did you become a pathologist?

I entered medical school relatively undifferentiated. I knew I wanted to have a stronger understanding of the underlying disease process, but I wasn’t sure where that would most apply. Going into my clinical years, I realized that I really enjoyed almost all of my rotations, which I thought would make my decision harder! But ultimately, I found that the underlying thread of interest in each of those specialties was the pathology that underpins the practice of medicine. I took a few path rotations from there and was absolutely hooked. I guess I’m also just a very visual and tactile learner, and pathology really fits my style.

What do you like most about being a pathologist?

I love so much of what I do, but if I had to pick one thing that I find most interesting, I would say it’s that moment when you’re sitting down at the scope with a resident, watching them puzzle through what they’re seeing. I get the chance to see where their mindset is at and help them to better organize the information in their head so they can have a deeper understanding of it. And next time, they’ll explain it to their co-residents or to the clinical team! That discussion and interplay at the microscope or grossing bench make it all worth it for me.

What is special about your subspecialty?

Bone and soft tissue pathology has seen a bit of a surge in popularity lately because of the growth of molecular classifications, which give the specialty a complex and rewarding day-to-day experience. It’s a lot of fun to learn about and make these extremely complicated diagnoses.

But I would say the most special thing to me about BST is that it takes a very big-picture approach to understand rather than just looking at a histology slide in isolation. I’m not a detail-oriented person (shocking, I know), and with BST, you can’t just focus on the small, high-power details. At high power, everything in BST looks “wrong”. I like that the focus is architectural and that the radiology and clinical information is often a requirement for making diagnoses.

How does your typical day go?

A typical day on my service is pretty variable, so I don’t always know what to expect when I get into work. I usually sign out with the fellows or residents for about an hour or two in the morning and the same for follow-ups in the afternoons. Throughout the day, I can expect calls from the gross room when there are complex cases and fairly consistent consultations from my colleagues. Because BST is often the wastebasket service, we’ll often be the final step after all other options have been exhausted. Depending on the day, the rest of the time is spent in prep for the next tumor board, meetings for our medical education committee that I chair, or research.

What is the most memorable experience you’ve had at work?

It’s tough to pick one particular experience or case since we get so many rare and fascinating cases on this service. Here’s one example that I found really memorable though. A consult was sent in to us for a patient with a history of breast cancer, which they treated with a mastectomy. Years later she presents with a mass in her rib underlying the previous mastectomy site, all signs pointing to recurrence. It was diffusely pankeratin positive with some GATA3 positivity, and the outside favored diagnosis was recurrent carcinoma. Looking through it, a few vacuolated cells and some vague vasoformative features popped out on my review, although the cytology was quite bland and had a prominent myxoid background. Some vascular markers confirmed and we made the diagnosis of an epithelioid hemangioma in the bone. Just reminds me to stay on my toes when it comes to IHC staining in mesenchymal tumors.

What most surprised you about being a pathologist?

The amount of talking, haha. I thought I’d just be hiding behind the scope, but I’m almost always in constant discussion with my colleagues and clinicians about the care of these patients.

Is there anything you know now that you wish you had known when you began working as a pathologist?

To myself as a resident, I would say, “Don’t be afraid of mistakes, don’t be afraid of being wrong, don’t be afraid of learning.”

What do you think you would be doing if you weren’t doing this?

Honestly, not sure. Maybe art? I think it’d be fun to be in animation. That or a career counselor at a university. I like trying to work out with someone what their goals are and how to achieve them.

Could you say a few words about your association with PathologyOutlines.com?

I started contributing to PathologyOutlines.com back in residency through the recommendation of a friend who was an author for the site at the time. I enjoyed the process, and throughout residency, I wrote more topics and participated in the Fellow / Resident Advisory Board. Recently, I was invited to the Editorial Board as a bone and soft tissue content editor. Check out the new update on molecular analysis in BST for my latest work!

You can follow Dr. Obeidin on Twitter / Twitch @anisapling.

To sign up for future Spotlight On e-newsletters and more, visit our Newsletters page and type your email in the box.

Note: This interview was originally emailed to our e-newsletter subscribers on May 4, 2023.

5 June 2023: Textbook Updates

We have posted updates of the following topics:

CNS & pituitary tumors > General > WHO classification
by Maria Martinez-Lage, M.D.
Topic summary: 2021 WHO classification, 5th edition (WHO CNS5) builds upon the updated fourth edition published in 2016 and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW). This fifth edition incorporates major changes including further advancing the role of molecular information in the diagnosis of CNS neoplasms, introducing the concept of CNS WHO grade distinct from WHO grade, grading within tumor type, endorsing the use of Arabic numerals for grading instead of Roman numerals and defining new entities based on molecular and histological characteristics. In addition to NOS (not otherwise specified), NEC (not elsewhere classified) is introduced.

Informatics, digital & computational pathology > Digital and whole slide imaging > WSI commercial platforms
by Nat Pernick, M.D.
Topic summary: Whole slide imaging has become increasingly adopted by pathologists as a tool to digitalize pathology. Here major manufacturers of whole slide scanners and 2 of each of their representative products are listed as a resource for the pathology community. Manufacturers listed here include 3DHISTECH, Akoya Biosciences, Bionovation Biotech, Grundium, Hamamatsu Photonics, Huron Digital Pathology, KFBIO Digital Pathology, Leica Biosystems, Mikroscan Technologies, Motic Digital Pathology, Nikon, Objective Imaging, OptraSCAN, Philips Healthcare, Pramana, PreciPoint, Roche Diagnostics, Scopio Labs, Visiopharm.

Small intestine & ampulla > Infectious disorders > Giardia lamblia
by Iresha Vithanage, M.B.B.S., M.D., Saroona Haroon, M.B.B.S.
Topic summary: Protozoan disease caused by Giardia lamblia / Giardia intestinalis, a common parasite that can be detected in small bowel biopsies; it can also be detected in stool. Asymptomatic colonization or acute or chronic diarrheal illness; can be histologically confirmed by visualization of the organisms. Common in areas with poor sanitation and limited water treatment facilities. Giardia intestinalis infection causes enterocyte damage and loss of brush border of the epithelial cells of the small intestine, which leads to shortening of microvilli and altered epithelial barrier function. Overall prognosis is good with treatment; dehydration can be life threatening for infants and pregnant women. Commonly treated by antibiotics such as metronidazole, tinidazole and nitazoxanide.

Soft tissue > Vascular > Benign > Lymphangioma
by Farres Obeidin, M.D.
Topic summary: Benign localized or diffuse vascular proliferation composed of lymphatic vessels. May be either microcystic or macrocystic in nature. Wide age range but predominant in children and young adults. Many lymphatic malformations show somatic mutations in PIK3CA. Clinical history and imaging studies can suggest a lymphangioma; usually diagnosed on simple excision or incidentally on biopsy. Benign with a generally excellent prognosis in adults; locally recurrent potential (~20% of tumors): younger age and presence of associated symptoms of infection, dyspnea, dysphagia or hemorrhage are associated with higher rates of recurrence. Treatment depends heavily on the clinical presentation, size and location; small or localized lesions are generally amenable to surgical resection.

Transfusion medicine > Therapeutic apheresis > Leukocytapheresis
by Brian D. Adkins, M.D., Garrett S. Booth, M.D., M.S.
Topic summary: Leukocytapheresis is the removal of white blood cells via apheresis. Therapeutic leukocytapheresis is performed to acutely lower a patient’s white blood cell (WBC) count due to symptoms associated with hyperleukocytosis or increased viscosity. Usually associated with acute myeloid leukemia (AML) with WBC > 100,000/μL, lymphoblastic leukemia / lymphoma (ALL) with WBC > 400,000/μL. Patients may present with disseminated intravascular coagulation (DIC), tumor lysis syndrome or hypoxic ischemic type injury. Usually performed emergently using femoral apheresis or a dialysis catheter, which do not require radiographic confirmation. Chemotherapy should be initiated as quickly as possible and should supersede leukocytapheresis if patients are asymptomatic.

2 June 2023: Weekly Roundup #122

Here’s what you need to know about PathologyOutlines.com this week:

1. Worldwide Directory of Pathologists Update

Congratulations to our Image Contest winners! Check out the winning images here.

We are excited about how our Worldwide Directory of Pathologists will help pathologists learn about each other and work better together. However, we are also concerned about keeping information as private as possible despite our free, no registration website. Towards this end, we prohibit anyone from copying or compiling Directory data to create their own databases or the equivalent and will take action against any violators. We intentionally do not provide lists of complete data for any searches and have restricted emails to show up only one at a time on an individual profile, not in any lists. Let us know if you have any comments or questions at Comments@PathologyOutlines.com.

2. Dr. Pernick’s Essay on HPV Related Cancers

Dr. Pernick’s new post on human papillomavirus (HPV) related cancers is important because almost every unvaccinated person who is sexually active will get HPV at some time in their life. Read it at natpernick.substack.com/p/human-papillomavirus-hpv-related and email any comments or questions to Nat@PathologyOutlines.com.

Electron microscopy of HPV type 16 capsid protein (Image source, Wikipedia page)

3. How Do Cancer Metastases Arise?

Dr. Pernick has posted Part 1 of a 4 part series, from a pathologist’s perspective, at pathologyoutlines.com/ccnblog/howmetastasesarise1.html. He welcomes your questions and comments at Nat@PathologyOutlines.com but unfortunately cannot provide medical advice.

1 June 2023: Textbook Updates

We have posted updates of the following topics:

Appendix > Appendicitis > Interval appendicitis
by Pu Ni, M.D., Qingqing Liu, M.D., Ph.D.
Topic summary: Interval appendectomy is usually performed in patients with complicated appendicitis (i.e., rupture) who are clinically stable; these patients are treated with initial antibiotic therapy or drainage followed by a delayed appendectomy. Clinical symptoms caused by acute appendicitis (e.g., abdominal pain, fever, poor appetite, etc.) usually improve after initial nonsurgical management. Interval appendectomy is often performed to exclude an appendiceal neoplasm. Radiological findings after initial nonsurgical management include normal appendix to inflamed appendix, presence of residual abscess or resolution of the abscess. Conservative treatment is effective in a high percentage of patients with acute appendicitis, with success rates ranging from 68% to 95% and a relative low recurrence rate of ~10%.

Cytopathology > Lung > Nondiagnostic
by Mir Yousufuddin Ali Khan, M.D., Vinod Shidham, M.D.
Topic summary: Lung cytopathology involves the assessment of specimens that can be categorized into exfoliative cytology (sputum, bronchial brushing, bronchial wash and bronchoalveolar lavage) and FNA cytology (percutaneous transthoracic and endobronchial ultrasound guided). Nondiagnostic / inadequate / insufficient specimen lacks sufficient material in quantity or quality for a reliable diagnosis. Most common causes are insufficient cellularity, cellular degeneration, poor preservation of cells and hemorrhagic samples. Bronchoalveolar lavage with fewer than 10 alveolar macrophages per 2 mm² using a high power field diameter of 0.5 mm, is considered inadequate. Risk of malignancy is 40% for a nondiagnostic specimen.

Kidney nontumor / medical renal > Glomerular disease > Focal segmental glomerulosclerosis (FSGS) > Focal segmental glomerulosclerosis-general
by Giorgio Cazzaniga, M.D., Vincenzo L’Imperio, M.D.
Topic summary: Group of podocytopathies with different etiologies presenting with focal and segmental glomerulosclerosis (FSGS) along with nephrotic or subnephrotic proteinuria. Distinction should be made between the nonimmune complex mediated disease (FSGS) and the pattern of injury (segmental and focal sclerosis) due to other underlying glomerular conditions (e.g., immune complexes). Recently proposed clinicopathological classification divided FSGS based on etiology into 3 categories: primary, secondary and genetic. ~30 – 60% of patients will inexorably progress to end stage kidney disease (ESKD) over a 5 – 10 year period of observation. High dose oral glucocorticoids is the first line immunosuppressive treatment for primary FSGS.

Prostate gland & seminal vesicles > Acinar / ductal adenocarcinomas > Microcystic adenocarcinoma
by Ankur Sangoi, M.D.
Topic summary: One of the unusual histological patterns of acinar adenocarcinoma; while often easier to recognize at radical prostatectomy given the juxtaposition to usual pattern acinar adenocarcinoma (incidence of 11%), deceptive morphology can be challenging to recognize on prostate biopsy (incidence of 1%). Cystic glands with marked dilatation at low power magnification but often showing luminal crystalloid, blue intraluminal mucin and prominent nucleoli at higher power magnification. Diagnosis: core needle biopsies or transurethral resection of the prostate; immunohistochemistry may be used to confirm the absence of basal cells. One of the important deceptively bland histological patterns of prostate cancer, alongside atrophic, pseudohyperplastic and foamy gland prostatic adenocarcinoma.

Soft tissue > General > Staging
by Borislav A. Alexiev, M.D.
Topic summary: Includes soft tissue tumors of intermediate (locally aggressive and rarely metastasizing) potential and malignant soft tissue tumors. Sarcomas arising within the confines of the dura mater, including the brain, are not optimally staged by this system. Locally aggressive soft tissue neoplasms, which may recur locally but have either no risk of metastatic disease or an extremely low risk of metastasis, are excluded from the AJCC soft tissue sarcoma staging system. Reporting of pT (tumor), pN (lymph node) and (when applicable) pM (metastasis) categories is based on information available to the pathologist at the time the report is issued; as per the AJCC, it is the managing physician’s responsibility to establish the final pathologic stage based upon all pertinent information.

31 May 2023: Image Quiz #109

Authors: David Suster, M.D., Alexander Craig Mackinnon, Jr., M.D., Ph.D.

A 62 year old patient presented with a 9 cm anterior mediastinal mass (see image below). What would help differentiate this lesion from a metastasis from a head and neck lymphoepithelioma-like thymic carcinoma?

Select an answer:

A. Detailed clinical history

B. Immunohistochemistry for p63 and cytokeratins

C. In situ hybridization for EBER

D. In situ hybridization for HPV

E. Next generation sequencing

See the answer

To sign up for our biweekly image quiz e-newsletters and more, visit pathologyoutlines.com/subscribe.html.

Note: This image quiz was originally emailed to our e-newsletter subscribers on May 30, 2023.

30 May 2023: Textbook Updates

We have posted updates of the following topics:

Bone & joints > Other chondrogenic tumors > Enchondroma
by Borislav A. Alexiev, M.D.
Topic summary: Enchondroma is a benign hyaline, cartilaginous tumor that arises within the medullary cavity of bone. Histology with typical encasement pattern (deposition of bone surrounding the tumor lobules, a sign of indolent growth). 20% of all cartilaginous tumors, second only to osteochondroma (30%); most common in 20 – 50 year olds. Increased levels of D-2-hydroxyglutarate (D-2-HG) can be detected in cartilage tumors with an IDH1 or IDH2 mutation. Most common presenting symptoms are pain, swelling and deformity. Asymptomatic enchondromas can be followed clinically and do not need to be treated. Management of symptomatic enchondroma lesions typically involves surgical management in the form of simple curettage with bone grafting.

CNS nontumor > Toxic and metabolic disorders > Radiation injury
by Palgun Nisarga, M.D., Kymberly A. Gyure, M.D.
Topic summary: Radiation therapy is commonly used as adjuvant therapy for malignant CNS neoplasms. Radiation injury mainly affects white matter and includes autonomic, cognitive and functional deficits. Typically classified based on time of appearance of symptoms: acute radiation induced brain injury (days to weeks); early delayed radiation induced brain injury (weeks to 3 – 6 months); late radiation induced brain injury (focal and diffuse, > 3 – 6 months). Unknown predisposing intrinsic factors (location treated, age, clinical status, tumor diagnosis and genetic susceptibility); partly identified extrinsic factors (dose / therapy technique). Oral corticosteroids used for symptomatic cases; resection with frozen section diagnosis; no known medical therapy for cognitive impairment.

CNS & pituitary tumors > Cysts > Arachnoid cyst
by Saman Seyed Ahmadian, M.D.
Topic summary: Arachnoid cysts are nonneoplastic, intracranial cerebrospinal fluid (CSF) filled spaces lined with arachnoid membranes. They are classified as primary developmental or secondary cysts. Primary developmental cysts occur due to the splitting of arachnoid membranes in utero, resulting in abnormal collections of CSF; 50 – 65% present in the middle cranial fossa / Sylvian fissure. Secondary cysts are less common and often occur after trauma, infection or surgery. CT and MRI are used for radiologic assessment; surgical resection is required for a definitive diagnosis. Clinical features depend on size and location: headaches are the most common symptom; arachnoid cysts can also be asymptomatic. Treatment: surgery if symptomatic.

Molecular markers > MYD88
by Yan Chen Wongworawat, M.D., Ph.D., Kevin E. Fisher, M.D., Ph.D.
Topic summary: MYD88 innate immune signal transduction adaptor; MYD88 gene (NM_002468.5) is located on chromosome 3p22.2 and has 5 exons. Somatic activating mutations in MYD88 are the most frequent molecular alteration in patients with lymphoplasmacytic lymphoma (LPL) and Waldenström macroglobulinemia (WM) and are seen in > 90% of cases. Inherited / germline mutations in this gene are associated with immunodeficiency 68 (ID68), an autosomal recessive primary immunodeficiency characterized by severe systemic and invasive bacterial infections beginning in infancy or early childhood. Detection of MYD88 activating mutations requires sequencing based methods such as Sanger sequencing, next generation sequencing or pyrosequencing.

Uterus > Endometrial hyperplasia > Progestin therapy related changes
by Carlos Parra-Herran, M.D.
Topic summary: Hysterectomy is the standard treatment for endometrial intraepithelial neoplasia (atypical hyperplasia) and low grade endometrial endometrioid adenocarcinoma. Hormonal therapy is a valid alternative for premenopausal women who desire to preserve fertility, as well as patients in which surgical treatment is not feasible. 2 main types of fertility sparing treatment are oral progestins and a levonorgestrel releasing intrauterine device. Factors associated with higher likelihood of remission under progestin therapy: young age, previous pregnancy, infertility, index diagnosis of endometrial intraepithelial neoplasia / atypical hyperplasia (versus endometrioid carcinoma) and treatment with megestrol acetate (versus other forms of treatment).

25 May 2023: Textbook Updates

We have posted updates of the following topics:

Anus & perianal area > Carcinoma > Adenocarcinoma
by Raul S. Gonzalez, M.D.
Topic summary: Rare adenocarcinoma that primarily involves the anal canal (not rectal adenocarcinomas with downward spread). May arise from anal glands, from congenital anorectal duplications or along a fistula tract. 5% of anorectal malignancies; slightly more common in white men. Proposed etiologic associations include chronic fistula, anal Crohn’s disease and anal sexual intercourse. Often a long history of perianal fistulas, abscesses, surgery; indolent course with gradual progression. Poor prognosis associated with advanced T and N category disease and higher histologic grade. Standard treatment includes abdominoperineal resection; adding chemotherapy and radiation improves outcome.

Anus & perianal area > Carcinoma > Paget disease
by Raul S. Gonzalez, M.D.
Topic summary: Intraepithelial tumor usually of apocrine or possibly eccrine gland origin. Intraepidermal neoplastic cells, sometimes linked to anal malignancy (secondary) but may also be primary disease. More common in older patients. Typically indolent but often recurs. Up to 40% of patients with anal Paget disease have secondary disease (associated with an underlying malignancy); usually adenocarcinoma but sometimes other forms, such as neuroendocrine carcinoma. Arises anywhere between the dentate line and the perianal skin. May be related to epithelial – mesenchymal transition. Diagnosis: tissue sampling. Treatment: wide local excision or radiotherapy.

Molecular markers > RAS Q61R IHC
by Leila Moayed-Alaei, M.D., Andrew J. Colebatch, M.B.B.S., Ph.D.
Topic summary: NRAS (neuroblastoma RAS viral oncogene homolog) is a proto-oncogene located on chromosome 1p13.2; mutant NRAS was first identified as a transforming gene in a neuroblastoma cell line (SK-N-SH). Strong and diffuse cytoplasmic or membranous staining of RAS Q61R is interpreted as positive staining. Diffuse and strong cytoplasmic or membranous staining is confined to myoepithelial cells in salivary gland neoplasms. Pitfall in IHC: the immunohistochemistry is not specific for NRAS Q61R mutation and will stain HRAS Q61R and KRAS Q61R as well. RAS Q61 immunohistochemistry is used by pathologists to identify mutation in codon 61 of HRAS, KRAS and NRAS gene.

Skin melanocytic tumor > Melanoma > Nodular melanoma
by Bethany R. Rohr, M.D.
Topic summary: Nodular melanoma (NM) is an aggressive histologic subtype of invasive malignant melanoma; it accounts for 16 – 25.6% of primary cutaneous melanomas. Nodular melanoma mutations overlap with other melanoma subtypes (both low and high cumulative sun damage). Most common in light skinned adults with history of intermittent or chronic sun damage. Pigmented or nonpigmented (pink) papule or nodule with rapid growth; frequently ulcerated. Diagnosis: scoop shave biopsy or excisional biopsy preferred; histopathologic diagnosis is gold standard. Thicker (Breslow) depth is the most important adverse prognosis indicator. Treatment includes excision with or without sentinel lymph node biopsy; additional treatment based on stage.

Soft tissue > Adipose tissue tumors > Liposarcoma > Dedifferentiated liposarcoma
by Susan Potterveld, D.O., M.P.H., Michael R. Clay, M.D.
Topic summary: Well differentiated liposarcoma (WDL) with transition, either in the primary tumor or as a recurrence to a sarcoma that is typically nonlipogenic. Molecularly characterized by ring or giant marker / rod chromosomes composed of material from 12q13-15; results in localized amplification of several neighboring genes, including MDM2. Although these tumors were originally all considered high grade, low grade dedifferentiation is now a recognized phenomenon. Typically occurs in older adults, with a slight predilection for men. Better prognosis than other high grade pleomorphic sarcomas but still recurs in 40 – 75% of cases, metastasizes in 10 – 15% of cases and is associated with a 28% mortality rate. Resectable disease is treated with surgery to obtain negative margins.

22 May 2023: Case of the Month #527

Thanks to Dr. Raul Gonzalez, Emory University School of Medicine, Atlanta, Georgia, USA for contributing this case and discussion and to Dr. Naziheh Assarzadegan, University of Florida, Gainesville, Florida, USA for reviewing the discussion.

Clinical history:

A 45 year old man presents to a gastroenterologist complaining of constipation and rectal bleeding. A single ulcerated rectal lesion is found on colonoscopy and is biopsied.

Click here for the case

All cases are archived on our website. To view them sorted by case number, diagnosis or category, visit our main Case of the Month page.

To subscribe to Case of the Month or our other email newsletters, visit pathologyoutlines.com/subscribe.html.

Note: This case was originally emailed to our e-newsletter subscribers on May 18, 2023.