The medical student's guide to pathology residency, fellowships, and careers.

Recent studies have shown that relatively few MD, DO, and underrepresented in medicine (URM) students and physicians are matching into pathology residency in the United States (US). In the 2021 Main Residency Match, just 33.6% of filled pathology residency positions were taken by senior year students at US allopathic medical schools. This has been attributed to the fact that pathology is not a required rotation in most US medical schools, pathology is often taught in an integrated curriculum in the US where is does not stand out as a distinct field, and because the COVID-19 pandemic led to a suspension of in-person pathology rotations and electives. Ultimately, many US medical students fail to consider pathology as a career pathway. The objective of this article is to provide medical students with basic information, in the form of frequently asked questions (FAQs), about pathology training and career opportunities. This was accomplished by forming a team of MD and DO pathology attendings, pathology trainees, and a medical student from multiple institutions to create a pathology guide for medical students. This guide includes information about post-sophomore fellowships, 5 major pathology residency tracks, more than 20 fellowship pathways, and allopathic and osteopathic board examinations. This guide also contains photographs and descriptions of major pathology sub-specialties, including the daily and on-call duties and responsibilities of pathology residents. The exciting future of pathology is also discussed. This guide supports the agenda of the College of American Pathologists' (CAP) Pathologist Pipeline Initiative to improve student recruitment into pathology.

Cre/loxP approach-mediated downregulation of Pik3c3 inhibits the hypertrophic growth of renal proximal tubule cells.

Nephron loss stimulates residual functioning nephrons to undergo compensatory growth. Excessive nephron growth may be a maladaptive response that sets the stage for progressive nephron damage, leading to kidney failure. To date, however, the mechanism of nephron growth remains incompletely understood. Our previous study revealed that class III phosphatidylinositol-3-kinase (Pik3c3) is activated in the remaining kidney after unilateral nephrectomy (UNX)-induced nephron loss, but previous studies failed to generate a Pik3c3 gene knockout animal model. Global Pik3c3 deletion results in embryonic lethality. Given that renal proximal tubule cells make up the bulk of the kidney and undergo the most prominent hypertrophic growth after UNX, in this study we used Cre-loxP-based approaches to demonstrate for the first time that tamoxifen-inducible SLC34a1 promoter-driven CreERT2 recombinase-mediated downregulation of Pik3c3 expression in renal proximal tubule cells alone is sufficient to inhibit UNX- or amino acid-induced hypertrophic nephron growth. Furthermore, our mechanistic studies unveiled that the SLC34a1-CreERT2 recombinase-mediated Pik3c3 downregulation inhibited UNX- or amino acid-stimulated lysosomal localization and signaling activation of mechanistic target of rapamycin complex 1 (mTORC1) in the renal proximal tubules. Moreover, our additional cell culture experiments using RNAi confirmed that knocking down Pik3c3 expression inhibited amino acid-stimulated mTORC1 signaling and blunted cellular growth in primary cultures of renal proximal tubule cells. Together, both our in vivo and in vitro experimental results indicate that Pik3c3 is a major mechanistic mediator responsible for sensing amino acid availability and initiating hypertrophic growth of renal proximal tubule cells by activation of the mTORC1-S6K1-rpS6 signaling pathway.

A 73-gene proliferative transcriptomic signature predicts uterine serous carcinoma patient survival and response to primary therapy.

OBJECTIVES: To develop a transcriptomic signature capable of predicting overall survival (OS) for uterine serous carcinoma (USC). METHODS: RNAseq data for 58 USC patients were obtained from TCGA. Expression of 73 candidate genes was measured for 67 Augusta University (AU) samples using NanoString technology. RESULTS: Analysis of the TCGA RNAseq data identified 73 genes that individually predict prognosis for USC patients and an elastic net model with all 73 genes (USC73) distinguishes a good OS group with low USC73 score from a poor OS group with high USC73 score (5-year OS = 83.3% and 13.3% respectively, HR = 40.1; p = 3 × 10-8). This finding was validated in the independent AU cohort (HR = 4.3; p = 0.0004). The poor prognosis group with high USC73 score consists of 37.9% and 32.8% of patients in the TCGA and AU cohort respectively. USC73 score and pathologic stage independently contribute to OS and together provide the best prognostic value. Early stage, low USC73 patients have the best prognosis (5-year OS = 85.1% in the combined dataset), while advanced stage, high USC73 patients have the worst prognosis (5-year OS = 6.4%, HR = 30.5, p = 1.2 × 10-12). Consistent with the observed poor survival, primary cell cultures from high USC73 patients had higher proliferation rate and cell cycle progression; and high USC73 patients had lower rates of complete response to standard therapy. CONCLUSIONS: The USC73 transcriptomic signature and stage independently predict OS of USC patients and the best prediction is achieved using USC73 and stage. USC73 may also serve as a therapeutic biomarker to guide patient care.

Expanding upon the Human Myometrial Stem Cell Hypothesis and the Role of Race, Hormones, Age, and Parity in a Profibroid Environment.

Uterine fibroids (UFs) are clonal, hormonally regulated, benign smooth-muscle myometrial tumors that severely affect female reproductive health, although their unknown etiology limits effective care. UFs occur fourfold more commonly in African American women than in Caucasian women, and African American women generally have earlier disease onset and greater UF tumor burden, although the mechanism of this ethnic disparity has not been identified. Recent findings have linked cancer (ie, tumor) risk to increased tissue-specific stem cell division and self-renewal and suggest that somatic mutations in myometrial stem cells (MyoSCs) convert them into tumor-initiating cells, leading to UF. Specifically, preliminary results in paraffin-embedded myometrial tissues have shown increased STRO-1+/CD44+ MyoSCs in African American versus Caucasian women. Using specific methods of flow cytometry and automated quantitative pathology imaging, a large cohort of myometrial samples were investigated to determine how the STRO-1+/CD44+ MyoSCs change with regard to a patient's race, age, parity, fibroid and hormone statuses, and the location of UFs within the uterus. We confirmed that the STRO-1+/CD44+ MyoSC population is expanded in African American women, is correlated with parity and fibroid number, and fluctuates with cyclic menstrual cycle hormone changes and age. Our data suggest that an expanded MyoSC population increases the formation of tumor-initiating cells, ultimately contributing to increased UF prevalence and burden in African American women.

Developmental Exposure to Endocrine Disruptors Expands Murine Myometrial Stem Cell Compartment as a Prerequisite to Leiomyoma Tumorigenesis.

Despite the high prevalence and major negative impact of uterine fibroids (UFs) on women's health, their pathogenesis remains largely unknown. While tumor-initiating cells have been previously isolated from UFs, the cell of origin for these tumors in normal myometrium has not been identified. We isolated cells with Stro1/CD44 surface markers from normal myometrium expressing stem cell markers Oct-4/c-kit/nanog that exhibited the properties of myometrial stem/progenitor-like cells (MSCs). Using a murine model for UFs, we showed that the cervix was a hypoxic "niche" and primary site (96%) for fibroid development in these animals. The pool size of these MSCs also responded to environmental cues, contracting with age and expanding in response to developmental environmental exposures that promote fibroid development. Translating these findings to women, the number of MSCs in unaffected human myometrium correlated with risk for developing UFs. Caucasian (CC) women with fibroids had increased numbers of MSCs relative to CC women without fibroids, and African-American (AA) women at highest risk for these tumors had the highest number of MSCs: AA-with fibroids > CC-with fibroids > AA-without fibroids > CC-without fibroids. These data identify Stro1+ /CD44+ MSCs as MSC/progenitor cell for UFs, and a target for ethnic and environmental factors that increase UF risk. Stem Cells 2017;35:666-678.

Amino acid metabolism inhibits antibody-driven kidney injury by inducing autophagy.

Inflammatory kidney disease is a major clinical problem that can result in end-stage renal failure. In this article, we show that Ab-mediated inflammatory kidney injury and renal disease in a mouse nephrotoxic serum nephritis model was inhibited by amino acid metabolism and a protective autophagic response. The metabolic signal was driven by IFN-γ-mediated induction of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity with subsequent activation of a stress response dependent on the eIF2α kinase general control nonderepressible 2 (GCN2). Activation of GCN2 suppressed proinflammatory cytokine production in glomeruli and reduced macrophage recruitment to the kidney during the incipient stage of Ab-induced glomerular inflammation. Further, inhibition of autophagy or genetic ablation of Ido1 or Gcn2 converted Ab-induced, self-limiting nephritis to fatal end-stage renal disease. Conversely, increasing kidney IDO1 activity or treating mice with a GCN2 agonist induced autophagy and protected mice from nephritic kidney damage. Finally, kidney tissue from patients with Ab-driven nephropathy showed increased IDO1 abundance and stress gene expression. Thus, these findings support the hypothesis that the IDO-GCN2 pathway in glomerular stromal cells is a critical negative feedback mechanism that limits inflammatory renal pathologic changes by inducing autophagy.

Altered Morphology and Immunohistochemical Characteristics in Metastatic Malignant Melanoma After Therapy With Vemurafenib.

Metastatic melanoma is traditionally diagnosed using classic morphologic features in addition to immunohistochemical studies. The authors report a case of metastatic malignant melanoma where both morphology and immunohistochemistry were altered after treatment. This 51-year-old patient presented with metastatic melanoma to the brain and axilla. Initially, both metastases showed classic morphology and diffuse staining with the pan-melanoma antibody cocktail. This cocktail is a combination of 3 antibodies commonly used to diagnose melanocytic neoplasms: Melan-A (MART-1), tyrosinase, and HMB-45. In combination, the cocktail is highly sensitive for detecting melanocytic neoplasms and is commonly used to diagnose metastatic melanoma. Her tumor was positive for the BRAF 1799T>A (V600E) mutation, and she was treated with BRAF inhibitor therapy (vemurafenib). However, the axillary tumor recurred after treatment with vemurafenib. The recurrent tumor showed a markedly different morphology and complete loss of staining with the pan-melanoma antibody cocktail. This loss of staining accompanied by the change in morphology was an observation not previously documented after therapy with vemurafenib. This case demonstrates a potential pitfall in the diagnosis of metastatic or recurrent malignant melanoma.

Combined endothelin a blockade and chlorthalidone treatment in a rat model of metabolic syndrome.

Experiments determined whether the combination of endothelin A (ETA) receptor antagonist [ABT-627, atrasentan; (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid] and a thiazide diuretic (chlorthalidone) would be more effective at lowering blood pressure and reducing renal injury in a rodent model of metabolic syndrome compared with either treatment alone. Male Dahl salt-sensitive rats were fed a high-fat (36% fat), high-salt (4% NaCl) diet for 4 weeks. Separate groups of rats were then treated with vehicle (control), ABT-627 (ABT; 5 mg/kg per day, in drinking water), chlorthalidone (CLTD; 5 mg/kg per day, in drinking water), or both ABT plus CLTD. Mean arterial pressure (MAP) was recorded continuously by telemetry. After 4 weeks, both ABT and CLTD severely attenuated the development of hypertension, whereas the combination further reduced MAP compared with ABT alone. All treatments prevented proteinuria. CLTD and ABT plus CLTD significantly reduced nephrin (a podocyte injury marker) and kidney injury molecule-1 (a tubulointerstitial injury marker) excretion. ABT, with or without CLTD, significantly reduced plasma 8-oxo-2'-deoxyguanosine, a measure of DNA oxidation, whereas CLTD alone had no effect. All treatments suppressed the number of ED1(+) cells (macrophages) in the kidney. Plasma tumor necrosis factor receptors 1 and 2 were reduced only in the combined ABT and CLTD group. These results suggest that ABT and CLTD have antihypertensive and renal-protective effects in a model of metabolic syndrome that are maximally effective when both drugs are administered together. The findings support the hypothesis that combined ETA antagonist and diuretic treatment may provide therapeutic benefit for individuals with metabolic syndrome consuming a Western diet.

Antihypertensive and anti-inflammatory actions of combined azilsartan and chlorthalidone in Dahl salt-sensitive rats on a high-fat, high-salt diet.

Metabolic syndrome (MetS) and chronic kidney disease are global health issues. Metabolic syndrome induces hypertension and commonly results in renal damage. The optimal therapy for hypertension in MetS is unknown. Thiazide diuretics are first-line therapy; however, these drugs may have untoward effects. In the present study we investigated the effects of azilsartan (AZL), chlorthalidone (CLTD) and their combination on blood pressure and renal injury in a rodent model with features of MetS. Dahl salt-sensitive rats were fed high-fat (36% fat), high-salt (4% NaCl) diet. Groups were then treated with vehicle, AZL (3 mg/kg per day), CLTD (5 mg/kg per day) or AZL + CLTD. Mean arterial pressure was recorded continuously by telemetry. After 26 days, rats were killed humanely and their kidneys were harvested for histology. Both AZL and CLTD attenuated the rise in blood pressure compared with vehicle and the combination further reduced blood pressure compared with CLTD alone. All treatments reduced proteinuria and albuminuria. Nephrinuria was prevented only in groups treated with AZL. Nephrinuria was 57% lower and proteinuria was 47% lower with combination therapy compared with AZL alone. All treatments reduced the number of inflammatory cells in the kidney. In conclusion, in our model, AZL and CLTD lower blood pressure and exhibit renal protective effects. Treatment with AZL offers additional protection, as evidenced by lower nephrinuria and plasma monocyte chemoattractant protein-1 levels. Combination therapy afforded the greatest protective effects and may be the best choice for hypertensive therapy in MetS.

A human monoclonal antibody against the collagen type IV α3NC1 domain is a non-invasive optical biomarker for glomerular diseases.

Progressive kidney disease is a significant clinical problem. However, despite research aimed toward developing improved predictors of disease, the major tool to assess kidney ultrastructure damage is the kidney biopsy. Here we tested the capability of a labeled human monoclonal antibody (F1.1), directed against the NC1 domain of α3(IV) collagen, to detect pathologic kidney alterations in vivo using mouse models of nephrotoxic serum-induced nephritis and puromycin aminoglycoside nephrosis. The F1.1 antibody-fluorophore conjugate signal rapidly localized specifically to injured glomeruli in both the severe and mild kidney disease models while minimally labeling healthy kidney. This differential labeling is likely due to cryptic NC1-domain exposure as enzymatic or chemical treatment of healthy human or mouse kidney sections significantly increased F1.1 binding to the glomeruli. Finally, kidney tissue from patients with renal disease show significant glomerular staining by F1.1 indicating that exposure of the NC1 domain occurs in clinically relevant circumstances. Thus, NC1 domain exposure may represent an in situ biomarker for assessment of kidney injury. Our study suggests that F1.1 and similar antibodies may represent a new class of non-invasive renal imaging reagents.

Lack of evidence for a remote effect of renal ischemia/reperfusion acute kidney injury on outcome from temporary focal cerebral ischemia in the rat.

OBJECTIVE: Acute kidney injury (AKI) and ischemic stroke may occur in the same cardiac surgical patient. It is not known if an interaction exists between these organ injuries. Isolated renal ischemia/reperfusion is associated with dysfunction in remote, otherwise normal organs, including the brain. In a rat model of simultaneous bilateral renal artery occlusion (BRAO) and middle cerebral artery occlusion (MCAO), the authors tested the hypothesis that AKI would worsen experimental stroke outcome. DESIGN: Sixty thermoregulated anesthetized rats were randomized to (1) 40-minute BRAO, (2) 80-minute MCAO, or (3) simultaneous BRAO + MCAO. Serum creatinine was measured at baseline and 2 and 7 days after organ reperfusion. Neurologic function and brain and kidney histologies were measured on day 7. In a parallel study, serum cytokines were measured over 16 hours. SETTING: Laboratory. PARTICIPANTS: Male Wistar rats. INTERVENTIONS: Combined or isolated BRAO and MCAO. MEASUREMENTS AND MAIN RESULTS: AKI was similar between the BRAO and BRAO + MCAO groups, with greater 48-hour creatinine increases (p < 0.02) and renal histopathologic scores (p < 0.001) in these groups than with MCAO alone. Neurologic scores correlated with cerebral infarct size (p = 0.0001). There were no differences in neurologic score (p = 0.53) and cerebral infarct volume (p = 0.21) between the MCAO and BRAO + MCAO groups. There was no association between cerebral infarct size or neurologic score and 48-hour creatinine increase. Interleukin-6 was increased during reperfusion (p < 0.0001), but a difference among groups was absent (p = 0.41). CONCLUSIONS: In contrast to the effects reported for AKI on normal remote organs, AKI had no influence on infarct size or neurologic function after experimental ischemic cerebral stroke.

Pleomorphic high grade endometrial stromal sarcoma with YWHAE gene amplification may be a novel variant with poor prognosis.

Endometrial stromal neoplasms are classified by the World Health Organization (WHO) into endometrial stromal nodule (ESN), low grade (LGESS), high grade (HGESS), and undifferentiated uterine sarcoma (UUS). HGESS is subclassified based on molecular findings, YWHAE or BCOR. The HGESS with YWHAE::NUTM2A/B (alias YWHAE::FAM22A/B) fusion usually have relatively monomorphic (as with most fusion-associated malignancies) rounded to epithelioid cells with eosinophilic cytoplasm, vesicular nuclei, nucleoli, and mitotic figures >10/10 HPF. We present a 66-year-old woman with post-menopausal bleeding found to have a heterogeneous solid-cystic uterine mass on CT who underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic lymph node dissection. A 15.0×9.0 cm variegated uterine mass with hemorrhage and necrosis was identified. Histologically, the tumor was hypercellular with haphazard fascicles, microcysts, and tongue-like destructive myometrial invasion. Tumor cells exhibited marked pleomorphism and high mitotic activity with atypical mitotic figures. There was extensive cyclin-D1 and subset CD10 immunopositivity. FISH showed YWHAE amplification but without rearrangement. Interestingly, we found only two other reported cases of pleomorphic HGESS with YWHAE gene amplification upon review of 259 cases from cBioPortal database, one of which was reported as carcinosarcoma with heterologous elements. Of note, all three YWHAE amplified cases were diagnosed at high-stage and succumbed to disease within six months. Our case appears to be the third case of YWHAE-amplified pleomorphic HGESS, possibly a new variant of uterine sarcoma with aggressive biologic behavior that needs further evaluation.

Recurring Norovirus & Sapovirus Infection in a Renal Transplant Patient.

Noroviruses and sapoviruses are common causes of gastroenteritis and infectious diarrhea. Although these viruses are typically of short duration in healthy individuals, immunocompromised organ transplant recipients can develop chronic, relapsing symptoms with grave outcomes. We discuss a unique case of chronic norovirus infection with subsequent sapovirus infection in a kidney transplant recipient. Relief of norovirus symptoms occurred after the reduction of immunosuppression and treatment with nitazoxanide. Subsequently, a superimposed sapovirus infection developed. Patient developed renal transplant rejection due to reduction of immunosuppression. Findings from this case study suggest that norovirus and sapovirus are associated with chronic, relapsing symptoms and significant morbidity in immunocompromised renal transplant patients and that reduction of immunosuppression in order to overcome infection risks allograft rejection. Early detection and management are essential to reduce morbidity associated with these viruses among immunocompromised transplant recipients.

Narrative Review of Hypercoagulability in Small-Vessel Vasculitis.

Pauci-immune necrotizing and crescentic glomerulonephritis (GN) is the most common etiology of rapidly progressive GN. Clinical presentation in those afflicted is usually related to rapid loss of kidney function. We report the case of a 70-year-old woman who came to medical attention for signs and symptoms related to lower-extremity deep vein thrombosis (DVT). At presentation, the patient had biochemical abnormalities consistent with active GN, which quickly progressed to rapid loss in kidney function requiring renal replacement therapy. Kidney biopsy revealed small-vessel vasculitis with glomerular crescents. Serologic studies were negative for antineutrophil cytoplasmic antibody antibodies and other causes of acute GN. Plasmapheresis, immunosuppressive, and anticoagulant therapies were prescribed. Absence of other apparent end-organ involvement with vasculitis pointed toward renal-limited small-vessel vasculitis, yet presence of unprovoked DVT argues for systemic vascular inflammation. This case illustrates that venous thrombosis can be the presenting manifestation in patients with vasculitis and silent, severe end-organ involvement. The epidemiology and pathophysiology of venous thromboembolism in small-vessel vasculitis are discussed in this report.

Crescentic IgA nephropathy along with simultaneous cellular and antibody-mediated rejection in a kidney transplant leading to rapid allograft failure.

Crescentic IgA Nephropathy in a renal transplant can lead to rapid loss of graft function despite treatment. Concurrent treatment-resistant acute cellular and antibody-mediated rejection make the prognosis even worse.

Clear Cell Myoepithelial Carcinoma Arising from the Hard Palate with Metastasis to the Lungs.

Myoepithelial carcinoma is an uncommon tumor of the salivary glands, most commonly the parotid gland. Clear cell myoepithelial carcinoma is a rare variant with an aggressive behavior. Here, we describe a case of clear cell myoepithelial carcinoma arising from the hard palate in an elderly male who underwent resection of the tumor and postop radiation. Posttreatment imaging demonstrated bilateral pulmonary nodules and a C2 body lesion concerning for metastasis. Biopsy of the lung lesions revealed a monomorphous population of optically clear cells with hyperchromatic and pleomorphic nuclei which were morphologically similar to the prior resection specimen. There are few reported cases of clear cell myoepithelial carcinoma arising from the hard palate, and there are even fewer reports on metastases to the lungs. Due to the low number of reported cases, prognosis and treatment of this neoplasm is not well defined.

Differential Expression of Prostaglandin E2 Receptors in Porcine Kidney Transplants.

BACKGROUND: Acute rejection of a kidney allograft results from adaptive immune responses and marked inflammation. The eicosanoid prostaglandin E2 (PGE2) modulates the inflammatory response, is generated by cyclooxygenase 2 (COX-2), and binds to 1 of the 4 G protein-coupled E prostanoid cell surface receptors (EP1-4). Receptor activation results in in proinflammatory (EP1 and EP3) or anti-inflammatory (EP2 and EP4) responses. We theorized that expression of the components of the COX-PGE2-EP signaling pathway correlates with acute rejection in a porcine model of allogeneic renal transplantation. METHOD: COX-2 enzyme and EP receptor protein expression were quantitated with western blotting and immunohistochemistry from allotransplants (n = 18) and autotransplants (n = 5). Linear regression analysis was used to correlate EP receptor expression with the Banff category of rejection. RESULTS: Pigs with advanced rejection demonstrated significant increases in serum PGE2 metabolites, while pigs with less rejection demonstrated higher tissue concentrations of PGE2 metabolites. A significant negative correlation between COX-2 expression and Banff category of rejection (R = -0.877) was shown. Rejection decreased expression of EP2 and EP4. For both receptors, there was a significant negative correlation with the extent of rejection (R = -0.760 and R = -0.891 for EP2 and EP4, respectively). Rejection had no effect on the proinflammatory receptors EP1 and EP3. CONCLUSION: Downregulation of COX-2 and the anti-inflammatory EP2 and EP4 receptors is associated with acute rejection in unmatched pig kidney transplants, suggesting that the COX-2-PGE2-EP pathway may modulate inflammation in this model. Enhancing EP2 and/or EP4 activity may offer novel therapeutic approaches to controlling the inflammation of acute allograft rejection.

Cystic fibrosis: newborn screening in America.

Cystic fibrosis is the most common lethal genetic disease in Caucasians, manifesting as progressive lung dysfunction, pancreatic insufficiency, and intestinal disease. CF was traditionally diagnosed clinically, either because of a family history or occurrence of meconium ileus, or as a result of intestinal malabsorption and chronic pulmonary disease. In 1979, it was discovered that immunoreactive trypsinogen was increased in neonatal dried-blood specimens on Guthrie cards, making it possible to screen neonates. During the past decades, survival rates of patients with CF have improved significantly (see Figure 5). To continue this progress, universal newborn screening has been implemented in many states as an addition to the arsenal of therapies and strategies to improve survival. National newborn-screening programs to identify CF patients after birth have been adopted for a number of years in Europe, Australia, and Canada. As expected, many benefits have been seen due to the early identification of CF patients, including improved survival, better lung function and growth with less intensive therapy, and reduced cost of therapy. To date, 37 states in the United States have adopted similar programs, in the hopes of improving CF outcomes. This welcome trend should help improve the lives of CF patients living in America.

Fewer seniors from United States allopathic medical schools are filling pathology residency positions in the Main Residency Match, 2008-2017.

Some pathologists have observed that fewer trainees from US medical schools are entering pathology residency. This trend was measured and further explored using Main Residency Match (MRM) data from 2008 to 2017, obtained from the National Resident Matching Program (NRMP). Over the past decade, there was an increase of 93 (508 in 2008 versus 601 in 2017, an 18.3% increase) pathology positions offered in the MRM. However, the proportion of pathology residency positions filled in the MRM which were taken by trainees from US medical schools decreased from 77.7% to 50.1% over this timespan. This was primarily due to fewer seniors from US allopathic medical schools filling pathology positions in the MRM (298 in 2008 versus 216 in 2017, a 27.5% decrease). Compared to 14 other medical specialties, pathology had the largest decline in the proportion of residency positions filled in the MRM which were taken by seniors from US allopathic medical schools (63.8% in 2008 versus 39.6% in 2017). Furthermore, pathology now has the lowest percentage of residency positions filled in the MRM, which were taken by seniors from US allopathic medical schools. The primary reason for this decline was because fewer seniors from US allopathic medical schools participated in the MRM for pathology positions (326 in 2008 versus 232 in 2017, a 28.8% decrease); however, the underlying reasons for this decline are unknown. In conclusion, over the past decade, substantially fewer seniors from US allopathic medical schools sought/filled pathology residency positions in the MRM. These findings are relevant for pathology residency recruitment, especially in the context of a projected decline in US pathologist workforce.