8 May 2024: Cancer Precursor Project – Characteristics of Premalignant Precursors, Part 3a (Dermatopathology)

Our cancer precursor project is intended to better understand how cancer arises by compiling a regularly updated spreadsheet of all distinct human cancers (now 1,232) and their precursors (now 191).

In part 1, we noted that the percentage of identified precursors varies widely by pathology subspecialty and we discussed precursors for subspecialties with epithelial sites (breast, head & neck, gyn, GI / liver, GU / adrenal and thoracic).

Epithelial malignancies, whether carcinomas or melanomas, typically have known risk factors associated with chronic inflammation, DNA changes, constitutive hormone production or immune system dysfunction. These risk factors promote changes in molecular pathways that produce intraepithelial neoplasia or dysplasia, in situ carcinoma and ultimately invasive malignancies.

In part 2, we discussed neuropathology related malignancies and their lack of precursors and speculated that contrary to current thinking, most nonepithelial malignancies may lack precursors. These nonepithelial malignancies often have no known risk factors and may arise from random processes or bad luck.

In the skin, of the 79 distinctive malignancies identified to date, only 6 malignancies have known precursors (5 melanocytic, 1 nonmelanocytic).

More text, images and links can be found at https://www.pathologyoutlines.com/dw/Cancerprecursorproject-characteristicsofpremalignantprecursorspart3adermatopathology.pdf.

Email any thoughts you have about this project to Nat@PathologyOutlines.com.

1 May 2024: Cancer Precursor Project – Characteristics of Premalignant Precursors, Part 2 (Brain and Eye Tumors)

The goal of our cancer precursor project is to better understand how cancer arises by compiling a regularly updated spreadsheet of all distinct human cancers (currently 1,232) and their premalignant precursors (currently 191).

In part 1 of this series, we noted that the percentage of identified precursors varies widely by pathology subspecialty and discussed precursors for subspecialties with epithelial sites (breast, head & neck, gyn, GI / liver, GU / adrenal and thoracic). In this essay, we discuss actual and possible malignant precursors associated with neuropathology.

Based on our work, it now appears that most brain and eye malignancies do not have a morphologic precursor. They may be initiated by a defining mutation in a single stem or progenitor cell or small cluster of cells that multiplies and acquires additional malignant properties over time. Due to its small size, detection may not be possible, at least with current methods, until it is large enough to be clinically evident.

Read more at pathologyoutlines.com/dw/Cancerprecursorproject-characteristicsofpremalignantprecursorspart2brainandeyetumors.pdf.

26 April 2024: Weekly Roundup #143

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

1. Curing Cancer Network April Newsletter

Make sure to read our Curing Cancer Network April newsletter here. If you’re interested in more, sign up to have these newsletters delivered directly to your inbox at lp.constantcontactpages.com/su/onz6IND.

2. New Board of Reviewers Appointments

Dr. Anna Biernacka was recently appointed to our new Board of Reviewers for Breast Pathology. Dr. Biernacka is an Assistant Professor of Pathology at the University of Chicago Medicine. She earned her M.D., Ph.D. from the Medical University of Lodz in Poland and then worked as a postdoctoral research fellow at MD Anderson Cancer Center and Albert Einstein College of Medicine. She then completed a residency in anatomic pathology at Baylor College of Medicine in Houston, followed by fellowships in cytopathology at Dartmouth-Hitchcock Medical Center and breast pathology at Massachusetts General Hospital.

Dr. Carlos Murga-Zamalloa was recently appointed to our new Board of Reviewers for Hematopathology. Dr. Murga-Zamalloa is an Assistant Professor of Pathology at the University of Illinois, Chicago. He obtained his M.D. at San Martin de Porres University (Lima, Peru). Dr. Murga-Zamalloa completed an anatomic and clinical pathology residency and a hematopathology fellowship at the University of Michigan, Ann Arbor. Dr. Murga-Zamalloa has an NIH funded research laboratory that focuses on the biology of T cell lymphomas, and he participates in multi-institutional international research projects to discover novel biomarkers and therapies in T cell lymphomas.  

3. Images of the Week

Here are some of our favorite images from topics posted recently:

Cervix > Clear cell carcinoma: Papillary pattern: papillae with central hyaline fibrous tissue cores are lined by hobnail cells with hyperchromatic nuclei (200x).
Contributed by Nadia Hameed, M.D.

CNS & pituitary tumors > Ependymoma: Perivascular pseudorosette with tightly packed processes is highly characteristic on smear prep.
Contributed by Chunyu Cai, M.D., Ph.D.

17 April 2024: Cancer Precursor Project – Characteristics of Premalignant Precursors (Part 1)

The goal of our cancer precursor project is to better understand how cancer arises by compiling a regularly updated spreadsheet of all distinct human cancers (1,232 as of April 12, 2024) and their premalignant precursors (191 identified to date).

Although premalignant precursors have been identified for 15.6% of distinct malignancies, the percentage varies widely by pathology subspecialty, from 1.8% to neuropathology (brain / eye) to 41.3% for thoracic (lung, heart, mediastinum).

We believe that studying these precursor lesions will help identify precursor lesions that we believe exist but are currently unknown, such as in the CNS (central nervous system or brain) and soft tissue.

This essay gives examples of precursors for carcinomas of the pancreas and lung and lists common precursors at other epithelial sites. More at pathologyoutlines.com/dw/Cancerprecursorproject-characteristicsofpremalignantprecursorspart1carcinomas.pdf.

3 April 2024: Cancer Precursor Project – Premalignant Precursors for Glioblastoma

The goal of our cancer precursor project is to better understand how cancer arises by compiling a regularly updated spreadsheet of all distinct human cancers (now ~1230) and their premalignant precursors (now ~190).

Malignant change is due to self organized criticality, which describes catastrophic events such as earthquakes, stock market crashes and malignant transformation. It is nature’s way of making large changes based on individual factors often thought too trivial to consider (Bak 1999). For example, in the punctuated equilibrium of species, one sees prolonged periods of apparent stasis (i.e., no new species), followed by bursts of new species (Eldredge & Gould 1972). During the quiet periods, minor changes accumulate that may not be noticed. Similarly, under the influence of cancer risk factors or random events, human biological networks may have prolonged periods of minor changes with no apparent clinical or microscopic changes, followed by bursts of activity leading to premalignant precursors or frank malignancy (Cross 2016, Pernick 2023).

We propose that premalignant precursors may be relatively stable based on the attractor concept and have distinctive molecular patterns that may or may not be identifiable histologically (Pernick 2018).

Glioblastoma, IDH wild type is the most common primary brain tumor in adults (primary in this context means not representing metastatic disease). It accounts for 14% of all primary central nervous system (CNS) tumors and 49% of all malignant CNS tumors in adults (Ostrom 2021).

Although we believe that most malignancies have a premalignant precursor lesion, to our knowledge, none have been identified for primary glioblastoma or any primary CNS tumor.

What might a glioblastoma premalignant precursor look like? We suggest it may have milder features of glioblastoma but in a nonmalignant context.

Read the full essay at pathologyoutlines.com/dw/Cancerprecursorproject-Premalignantprecursorsforglioblastoma.pdf.

26 March 2024: Cancer Precursor Project – Neuroendocrine Tumors

This is our first essay discussing malignancies and their precursor lesions based on our new Cancer Precursor Project. We have compiled a spreadsheet of all distinct human cancers (~1,230) and their identifiable precursors (~180). Please email proposed updates to Nat@PathologyOutlines.com.

Our goal is to identify precursor lesions for all malignancies to better understand and treat cancer and reduce its 600,000 annual U.S. deaths. Studying known precursors and their patterns of molecular expression may suggest molecular patterns for tumors with unknown precursors (Pernick 2018).

This essay discusses data compiled by our project on neuroendocrine tumors and summarizes current knowledge about 2 precursor lesions, one in the stomach (enterochromaffin-like cell hyperplasia) and one in the lung (diffuse idiopathic pulmonary neuroendocrine hyperplasia).

Read the full essay at pathologyoutlines.com/dw/Cancerprecursorproject-Neuroendocrinetumors.pdf.

6 March 2024: Understanding Cancer Precursors

Dr. Nat Pernick is compiling a database of all malignant lesions and their precursor lesions to better understand how cancer arises. He is inviting the worldwide pathology and scientific community to review and update this list by emailing him at Nat@PathologyOutlines.com. The current version is at docs.google.com/spreadsheets/d/14cosItHiVoH8EahECAs_Hua3BYBPxxaIDTXs9kunkQo/edit.

Specifically, he is interested in studying:

• The molecular patterns of known cancer precursors to help us identify precursors for specific cancers that are not yet known.
• The reasons why known precursors are identifiable histologically (i.e., what patterns of molecular expression produce notable cellular changes). This may help us recognize precursors histologically with subtle cellular changes.
• Do normal appearing cells adjacent to a malignancy with no known precursor have the same molecular characteristics as the malignancy? If so, does this represent a precursor? Let Dr. Pernick know what you think.
• How many distinct types of malignancies are there? To our knowledge, this information is not currently available. Our current estimate is 1,800 diagnoses distinct types based on the list to date (~450 entities; the list is 25% done).

Do you have expertise in particular malignancies? If so, we invite you to advise:

• What malignant diagnoses should be added or removed from this spreadsheet?
• What precursor lesions should be added or changed for any of the diagnoses listed?
• Are some diagnoses duplicative because they are essentially the same within or at different sites?

This is a work in progress. Dr. Pernick plans to update this list to include all human malignancies by April 2024 and as needed based on comments sent to Nat@PathologyOutlines.com.

See more at pathologyoutlines.com/dw/Understandingcancerprecursors-byNatPernick.pdf.

1 March 2024: Weekly Roundup #139

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

1. February 2024 Curing Cancer Network Newsletter

Read the February 2024 Curing Cancer Network newsletter in its entirety here: myemail.constantcontact.com/Curing-Cancer-Network-Newsletter.html?soid=1102437360197&aid=YjmUFJ_aEQM

To sign up for this newsletter that comes out every 1 – 2 months, visit lp.constantcontactpages.com/su/onz6IND.

2. Pathology Jobs Report

The fourth quarter PathologyOutlines.com Jobs report for 2023 has been posted on our Jobs page here. For this quarter, PathologyOutlines.com listed 339 full or part time pathologist job postings, which form the basis for the statistics within the report. We excluded postings that were only for locum, Ph.D., residency, fellowship or nonpathologist positions. Click here for full details of the report.

3. How Metastases Arise Part 3b-1: What Cells Normally Migrate

In this series of essays, Dr. Pernick explores what we know about metastases and speculates on future knowledge and treatment. In one of his recent essays, Dr. Pernick discusses the cells that normally migrate. This is important because cancer cells hijack the migration mechanisms used by these cells when they metastasize. You can read this essay at pathologyoutlines.com/ccnblog/howmetastasesarise3b-1.html.

4. How Metastases Arise, Part 3b-2: How Cells Normally Migrate

Dr. Pernick has written an essay describing the process through which cells normally migrate in the human body, which you can read at pathologyoutlines.com/ccnblog/howmetastasesarise3b-2.html. This is not only important in understanding how our body normally works but also in understanding cancer because the malignant process hijacks these mechanisms to produce metastases, the major cause of cancer deaths.

12 January 2024: Weekly Roundup #137

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

1. Curing Cancer Network December Newsletter

Read our December Curing Cancer Network newsletter at conta.cc/3HeiEiz. If you’re interested in more, sign up to have these delivered directly to your inbox at lp.constantcontactpages.com/su/onz6IND.

2. Urethral Lesions Topics

We have moved topics about urethral lesions from the Prostate and Vulva chapters to the newly named Bladder & urothelial tract chapter.

3. PathologyOutlines.com Merchandise

For a limited time, from today to January 16th, our merchandise shop is offering free shipping. There will also be a 20% off sale from January 17th through 21st. Check out what we have to offer now at pathologyoutlines.myspreadshop.com!

5 January 2024: Curing Cancer Network Essays

Part of Dr. Pernick’s Curing Cancer Network (CCN) activities is to post images and short essays about different types of cancer from a pathologist’s perspective for the general public. The regularly updated index to his cancer and medical posts is here, but he has provided links to the essays written to date at natpernick.substack.com/p/curing-cancer-network-essays-on-various.

Note: these essays are hosted at PathologyOutlines.com but they are independent of the PathologyOutlines.com textbook and are not peer reviewed by our Editorial Board.

Some excerpts of these essays are pasted below.

1. Bile Duct Cancer

Bile duct cancer, also called cholangiocarcinoma, is typically discussed with liver cancer because the bile ducts originate in the liver. However, the cells of bile duct cancer resemble bile ducts and not liver cells, and these cancers behave differently from liver cell cancer (also called hepatocellular carcinoma).

Bile duct cancers are rare, with an estimated 8,000 new cases in the U.S. each year. They may be intrahepatic (i.e., originating within the liver), with an incidence of 1.5 cases per 100,000 U.S. population) or extrahepatic (i.e., originating from ducts outside of the liver, such as the common hepatic duct and the common bile duct) with an incidence of 1.0 cases per 100,000 population.

Read more at natpernick.substack.com/p/bile-duct-cancer.

Extrahepatic tumor contains small, dispersed glands and single cells in a haphazard appearance.
Contributed by Raul S. Gonzalez, M.D.

2. Liver Cancer

Liver cancer combined with intrahepatic bile duct cancer is the #6 cause of cancer death in the U.S. (after lung, colon, pancreas, breast and prostate cancer), with 29,380 deaths projected in 2023 (19,000 in men, 10,380 in women). Many famous people have died of liver cancer, including musician Gregg Allman (attributed to a dirty tattoo needle and hepatitis C) and comedian Flip Wilson (cause unknown).

Liver cancer typically refers to primary liver cancers (i.e., cancers that originate in the liver and resemble liver cells). About 80% of primary liver cancers are liver cell cancer (hepatocellular carcinoma). The rest are usually cancer of the intrahepatic bile ducts (cholangiocarcinoma).

Read more at natpernick.substack.com/p/liver-cancer