cytopathology – Lablogatory

Thyroid Tales (First Edition)

I’ve found that our cytologists have a love-hate relationship with thyroids. Pathologists do too. Or it could be that we see so many goiters (50%) and follicular lesions or atypia of undetermined significance (35%) that the rare papillary thyroid carcinoma is a gem in our eyes. Minimally-invasive thyroid FNAs are instrumental in the management of thyroid nodules. It’s important to note that due to lack of architecture and assessment of capsular invasion, cytologic diagnoses may be limited, and prior to referring the patient for a potentially unnecessary surgery, various molecular tests can be utilized. The ongoing evolution of molecular testing on thyroid FNAs help classify indeterminate and suspicious cytology diagnoses (Bethesda Categories III and IV), examining the risk of malignancy or detecting the presence of genetic alterations, which help guide surgical intervention versus surveillance. This post (the first edition) features a series of our classic Bethesda Category VI specimens, which bypassed the need for risk classification and defaulted in surgical intervention based on guidelines at the time of diagnosis. It is worth mentioning that many of these cases occurred prior to the implementation of the Thyroid Imaging Reporting and Data System (TI-RADS), so to preserve the accuracy of patient history, a TI-RADS score will not be assumed.

Case 1

Okay, I know I said Bethesda VI, but let’s kick this series off with a Bethesda Category IV case. Thankfully, the patient decided to undergo a partial thyroidectomy, yielding a beautiful tissue follow-up. A 59-year-old male with newly diagnosed melanoma of the neck underwent imaging for staging purposes. A left thyroid nodule was identified measuring 3.0 centimeters. The patient presented for an ultrasound-guided fine needle aspiration.

Images 1-3: Thyroid, Left Lobe, FNA 1: DQ-stained smear; 2: Pap-stained smear; 3. H&E Cell Block section (400X).

Abundant oncocytic Hürthle cells, some with mild atypia, were identified, suggestive of Hürthle cell neoplasm (Images 1-3). With a lack of lymphocytes, we did not feel comfortable suggesting Hashimoto’s (lymphocytic) thyroiditis. Immunostains performed on cell block sections show the tumor cells are positive for TTF-1, focally positive for thyroglobulin and AE1/AE3 (rare), and negative for calcitonin. The morphology and immunohistochemical profile support the above diagnosis.

The patient underwent a left lobectomy and isthmusectomy. Pathology showed a 3.2 cm Hürthle cell carcinoma (Images 4-5) in the left lobe of the thyroid (encapsulated with a foci of capsular invasion without vascular invasion) as well as a 0.3 cm micropapillary carcinoma. Since Hürthle cell carcinoma does not typically concentrate radioiodine, the patient would not be responsive to treatment with radioactive iodine. Therefore, there would be less benefit derived from treating the smaller right lobed nodules (which don’t meet biopsy criteria) from remnant ablation. The patient had a clinically limited stage thyroid cancer. The patient is monitored with neck ultrasounds rather than serum thyroglobulin testing (due to the remaining right lobe).

Images 4-5: Thyroid, Left Lobe with Isthmus, Excision: H&E section (600X).

Cytology diagnosis: Hürthle cell neoplasm.

Pathology diagnosis: Hürthle cell carcinoma.

Case 2

A 53-year-old female with no prior history presented with fatigue and a self-palpated right thyroid nodule and normal thyroid function tests. She reported an extensive family history of hypothyroidism. On thyroid ultrasound, the right upper pole thyroid nodule measured 2.0 x 2.0 x 1.8 cm and was mostly solid and hypoechoic with microcalcifications. Pre-intervention serum calcitonin measured 1634 pg/mL. The patient underwent an FNA of the thyroid nodule and the smears are depicted below.

Images 6-7: Thyroid, Right Lobe, Upper Pole, FNA: 6: DQ-stained smear; 7: Pap-stained smear.

Cells appear plasmacytoid and appear both isolated and in clusters (Image 6). The nuclei are eccentrically placed, and the chromatin has a salt and pepper appearance akin to a neuroendocrine tumor (Image 7-8). Also identified were pink granules and intranuclear pseudoinclusions (Images 6-7). We performed immunohistochemical stains on paraffin sections of the cell block. Tumor cells show positive staining for calcitonin, chromogranin, mCEA, and TTF-1, while negative staining for thyroglobulin and CD45.

Following the diagnosis, the patient had a CT scan for staging purposes. Multiple lymph nodes in the right cervical chain were identified. the patient at a clinical stage IVA diagnosis. In the interim, the patient had a total thyroidectomy which revealed medullary thyroid carcinoma of the right lobe measuring 2.2 cm, a micropapillary carcinoma of the left lobe measuring 0.1 cm (Image 8). Lymphovascular invasion was not identified, the inked surgical resection margins are free of carcinoma, and metastatic medullary carcinoma was identified in 6 of the 77 lymph nodes removed during the central compartment lymph node dissection, and bilateral cervical lymphadenectomies. The calcitonin level dropped to 23 pg/mL postoperatively. Genetic testing was performed to assess for Multiple Endocrine Neoplasia Type 2 (MEN2), and although her result was indeterminate, a RET mutation was not identified.

Image 8: Thyroid, Excision: H&E section (600X).

Case 3

A 67-year-old male with no pertinent medical history presented to the endocrinology clinic after his primary care physician identified a large lump in the patient’s neck. A 7.0 cm hypoechoic right thyroid mass with macrocalcifications was noted on ultrasound imaging. The patient was referred to diagnostic imaging for a thyroid FNA. The smears and cell block section are depicted below. While the papillary formation of Image 9 is not evident on the pap-stained slide (Image 10), the nuclear grooves and pseudoinclusions along with irregular nuclear membranes and powdery chromatin are highlighted. A separate needle pass was collected for molecular testing, which revealed a BRAF V600E mutation in the tumor cells.

Images 9-11: Thyroid, Right Lobe, FNA 9: DQ-stained smear; 10: Pap-stained smear; 11. H&E Cell Block section (600X).

Two weeks after the FNA diagnosis, the patient was scheduled for a partial thyroidectomy of the right lobe. While 60% of the mass demonstrated well-differentiated papillary thyroid carcinoma (Image 12), 40% of the tumor contained poorly differentiated thyroid carcinoma with squamous features (Image 13). No sarcomatous components or giant tumor cells were identified. Carcinoma with squamous features invaded into the surrounding tissue, strap muscle, thymus, and right paratracheal lymph node. Interestingly, the right-sided levels 3 and 4 lymph nodes contained predominantly well-differentiated papillary thyroid carcinoma with rare foci of poorly differentiated thyroid carcinoma with squamous differentiation.

Images 12-13: Thyroid, Right Lobe, Excision: H&E section (600X).

Five months after the excision, the patient developed a left-sided pleural effusion. A diagnostic thoracentesis was performed and metastatic thyroid carcinoma was identified. Immunostains performed on the cell block slides with adequate controls show that the tumor cells are positive for PAX8, and negative for TTF-1, and thyroglobulin. The findings support the diagnosis. While patients with papillary thyroid carcinoma tend to have better disease-free survival rates, the poorly differentiated tumor was difficult to control and eventually resulted in widespread metastasis.

Cytology diagnosis: Papillary thyroid carcinoma.

Pathology diagnosis: Poorly differentiated thyroid carcinoma with squamous features in a background of well-differentiated papillary thyroid carcinoma.

Case 4

A 73-year-old female presented with a rapidly growing and painful thyroid mass that measured 8 cm on imaging. Originating from the right lobe, multiple needle passes targeted various areas of the mass via ultrasound-guidance. The smears and cell block section are presented below. Smears (Images 14-15) feature pleomorphic nuclei in a background of inflammation and necrosis. The cell block section (Image 16) demonstrates increased mitotic figures and neutrophils.

Images 14-16: Thyroid, Right Lobe, FNA: 14: DQ-stained smear; 15: Pap-stained smear; 16. H&E Cell Block section (600X).

We performed immunocytochemical stains on paraffin sections of the cell block. Tumor cells how positive staining for p53, focal staining for cyclin D1, and negative staining for AE1/AE3, thyroglobulin, and BCL-2. Rare tumor cells show staining for TTF-1. The proliferation index by Ki-67 immunostaining is approximately 70%.

While not a standard procedure for thyroid specimens, core biopsies (Image 17) were also obtained from this mass.

Molecular testing on the core biopsy sample identified a high mutation burden, with the tissue harboring both TP53-inactivating and TERT promoter mutations. Imaging demonstrated widespread metastasis, and this patient did not survive the extensiveness of her disease.

Cytology Diagnosis: Undifferentiated (anaplastic) thyroid carcinoma.

Pathology Diagnosis: High-grade carcinoma consistent with anaplastic carcinoma (interchangeable diagnoses).

That’s enough for our classic thyroid cases. Stay tuned for the second edition featuring thyroid FNAs with unsuspecting findings!

-Taryn Waraksa-Deutsch, MS, SCT(ASCP)^CM, CT(IAC), has worked as a cytotechnologist at Fox Chase Cancer Center, in Philadelphia, Pennsylvania, since earning her master’s degree from Thomas Jefferson University in 2014. She is an ASCP board-certified Specialist in Cytotechnology with an additional certification by the International Academy of Cytology (IAC). She is also a 2020 ASCP 40 Under Forty Honoree.

Histio Makes History

An 81 year old female presented to the head and neck clinic after being diagnosed with cutaneous T cell lymphoma of the posterior mid-parietal scalp at an outside institution. She was initially treated with Brentuximab every three weeks but developed significant toxicities. The patient’s previous “T cell lymphoma” material was reviewed at our institution and the immunophenotypic report described the neoplastic cells as being positive for CD45, CD2, CD4, BCL6+, CD3 (subset), and CD123 (scattered), while negative for CD7, CD8, CD20, CD30, CD56, EBER ISH, PAX5, and lysozyme. Immunohistochemical slides were not provided for review. Flow cytometric analysis determined that there was no immunophenotypic evidence of a clonal T cell population in the patient’s peripheral blood.

A second scalp biopsy was performed at another outside institution, and the findings were similar to the parietal scalp; however, there were atypical pleomorphic cells which displayed irregular contours, hyperchromasia, and multiple nucleoli. The atypical cells were predominantly positive for CD4 and diffuse positivity for CD1a. These same pleomorphic cells were negative for CD3, CD8, CD20, CD30, ALK1, BCL6, CD56, EBER, AE1/AE3, SOX10, Desmin, PAX5, MUM1, CD5, and Cam 5.2.

The smears contained large, highly pleomorphic cells with irregular, elongated, and multilobated nuclei, frequent nuclear grooves and folds, fine chromatin, prominent nucleoli, and variable amounts of pale, eosinophilic cytoplasm, alt.

The outside tissue block on the original scalp biopsy was requested, and our pathology department performed additional immunostains. The neoplastic cells of interest were positive for CD1a, S100, CD68 (a small subset), and negative for lysozyme, CD21, CD30, and CD3. Ki67 proliferation index was interpreted at approximately 60%. An unstained FFPE tissue section was sent to a reference laboratory, and the neoplastic cells were strongly positive for Langerin.

While the Brentuximab treatment initially appeared to have a positive impact on the overall disease burden, the PET CT following 3 cycles showed a mixed response, including resolution of cervical lymphadenopathy and identification of multiple new lung nodules and bulky mediastinal lymphadenopathy. Between that and numerous reported toxicities, the treatment protocol was discontinued. The patient was then referred to radiology for a CT-scan guided right lower lobe lung biopsy measuring 2.2 x 1.3 centimeters with an SUV or 29.6.

In the CT Scan suite, we received multiple FNA passes from the interventional radiologist and made air-dried and alcohol-fixed smears, rinsing the residual needle material into a tube of balanced salt solution for a cell block preparation. We determined our specimen was adequate for scant tumor cells, as depicted on the Diff-Quik smears below.

Images 1-2. Lung, right lower lob, CT-guided FNA. Diff-Quik stained smears.

In comparison to the material from the second scalp biopsy, the cells from the lung biopsy appeared identical. Our Pap-stained smears and H&E cell block sections also demonstrated the highly pleomorphic cells described above.

Images 3-6. Lung, Right Lower Lobe, CT-guided FNA. 3-4: Pap-stained smears, 5-6: H&E sections (5: 100x, 6: 400x).

Immunostains performed on the cell block slides with adequate controls show that the tumor cells are positive for CD1a, CD4, partially positive for CD45 and S100, negative for AE1/3, TTF-1, and p40.

Images 7-8. Lung, Right Lower Lobe, CT-guided FNA. Cell block section immunohistochemistry. 7: CD1a-positive; 8: partially S-100-positive.

Our pathologists felt the cells from the second scalp biopsy and the lung biopsy were representative of a Langerhans cell sarcoma, a form of malignant histiocytosis, rather than a T-cell lymphoma. It is possible that the first scalp biopsy’s diagnosis of T-cell lymphoma was due to sampling error and the pleomorphic cells of interest were missed. The Ki-67 proliferative index of 60% helped to distinguish between Langerhans cell histiocytosis and Langerhans cell sarcoma.

Molecular testing performed on the core biopsy was negative for a BRAF mutation and positive for an NF1 inactivating mutation. The tumor may then be sensitive to mTOR inhibitors and MAPK pathway inhibitors, such as MEK inhibitors. Appeals for a MEK inhibitor were denied by insurance, but fortunately, the tumor also demonstrated high PD-L1 expression at 90%, making this specific patient a candidate for pembrolizumab, which was fully covered by insurance.

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I can’t help but think about the disparities associated with cancer and the inaccessibility of potentially lifesaving or life-prolonging treatments. Sure, there may be viable alternatives, such as this case, but what if we had equal access to cutting edge, personalized therapies? What if the only therapy available was too costly to bear? Just because a cancer might be rare, such as Langerhans cell sarcoma, it doesn’t mean access to a proven effective therapy should also be rare. Even with drug assistance programs, so many patients face the harsh reality of tapping into their life savings to just to save their own life. When we became medical laboratory professionals, we promised to provide timely and accurate for all of our patients. Now, it’s time that pharmaceutical companies and our healthcare system as a whole work together to provide high quality, low-cost, readily accessible and personalized treatment options to every patient. They deserve that chance to overcome or at least manage their cancer.

Tumor on the Brain

Back in my Master’s program at Jefferson, I fondly remember the week we covered central nervous system (CNS) tumors. I was fascinated by the mnemonic tools we would use to identify different CNS tumors, such as “fried eggs” for oligodendrogliomas, perivascular pseudorosettes in ependymomas, and the whorling associated with meningiomas. Fortunately, for our patients, and unfortunately, for our diagnostic curiosity, we rarely see CNS tumors at my institution. Brain lesions resulting from metastatic carcinomas are typically well-identified via imaging and treated appropriately by the surgical, medical, and radiation oncology teams, but cytologists are available to screen cerebrospinal fluids (CSFs) for CNS involvement. For primary CNS tumors, however, we’re left recollecting the core memory of the second semester of our didactic phase. When a metastatic CNS tumor made its way into our lab, our cytology team swooned with excitement. (Yes, I know, but please introduce me to a lab professional who doesn’t embrace their quirks.) A 27-year-old male patient presented to radiation oncology three years after surgical debulking of a brain tumor at an outside institution. The patient, who was referred to radiation oncology at to treat the residual tumor at the original institution, did not follow up and developed an 8 centimeter recurrence a year after the initial resection. At this point, the patient experienced complete vision loss and underwent a biparietal-occipital craniectomy. A repeat brain MRI was performed a year later, and once again, a large enhancing extra-axial mass was identified along with multiple smaller masses also increasing in size. The patient received radiation after worsening difficulty with ambulation. After almost completing the planned fractions of radiation, the patient elected to stop their radiation therapy due to worsening seizures. A left neck mass was identified six months prior, and while the mass had not grown or caused pain, the patient was referred to head and neck surgical oncology for evaluation. Surveillance imaging demonstrated an enlarged left level 5A lymph node, suggestive of metastatic disease. Multiple ultrasound-guided fine needle aspiration biopsies were obtained from the lymph node, and ROSE was performed. The Diff-Quik-stained and concurrent Pap-stained smears demonstrated lesional tissue, although everything from epithelioid histiocytes to spindle cell melanoma to a renal primary were considered as a differential. Based on the location, a salivary gland primary was also a possibility for this case. The streaked cytoplasm and pseudoinclusions in both smears were concerning for a metastasis of the patient’s primary CNS tumor, but we were still hesitating to make the call.

Images 1-4. Lymph Node, Neck, Left, Level 5A, US-guided FNA. 1-2: Diff-Quik-stained smears, 3-4: Pap-stained smears.

The following morning, the H&E-stained FFPE cell block sections demonstrated the characteristic whorls expected for the patient’s primary, although the idea of metastasis was uncanny.

Images 5-6. Lymph Node, Neck, Left, Level 5A, US-guided FNA. H&E sections (6: 100x, 7: 400x).

We then used immunohistochemical studies to confirm our morphologic diagnosis. Immunostains performed on the cell block slides with adequate controls show that the tumor cells are positive for vimentin and PR (focal), while negative for AE1/AE3, EMA, CK7, CK20, TTF-1, Napsin A, p40, Pax8, synaptophysin, and S-100. The Ki-67 proliferation index fell at 18%, which is consistent with intermediate aggressive disease in a WHO Grade 2 atypical meningioma.

Images 7-8. Lymph Node, Neck, Left, Level 5A, US-guided FNA. Cell block section immunohistochemistry. 7: Vimentin-positive; 8: focally PR-positive.

The patient had next gen sequencing performed on his tissue, which demonstrated an NF-2 mutation, indicating he may benefit from MTOR inhibitors, but he elected not to pursue systemic therapy.

Where meningiomas account for 36% of primary brain tumors, atypical meningiomas comprise only 5-15% of all meningiomas (Cai et al., 202. Extracranial metastasis of atypical meningioma is a rare event, with only a few cases documented in the literature. While meningioma metastases are uncommon, a thorough collaboration between clinical impression and pathologic interpretation is necessary to ensure the possibility is not entirely excluded.

References

Cai C., Kresak J.L., Yachnis A.T. (2021) Atypical meningioma. Pathology Outlines. Retrieved October 11th, 2022, from https://www.pathologyoutlines.com/topic/cnstumoratypicalmeningioma.html.

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Triaging Times

As a clinical instructor and lead cytologist at my institution, I like to remind our newer cytologists and cytology students of the importance of being prepared for FNA biopsies so they develop good habits or best practices as they become more experienced. This level of preparation helps to create a culture of ongoing learning and improvement, which is necessary for the laboratory. In my experience, I’ve met some cytologists who prefer to go into a case blind, with the mindset that knowing the patient’s clinical history in advance muddies their knowledge, skills, and abilities, limiting their mindset by excluding the possibility of other diagnoses. While diving into the unknown might seem exciting, it is also a hindrance and could result in errors, especially when the clinical history helps us triage the patient’s sample. For example, knowing that the patient has a history of lymphoma or that the presentation state includes bulky lymphadenopathy prompts us to collect additional needle passes to send for flow cytometry analysis. Another concern is not knowing whether the patient has a history of breast, gastric, or esophageal cancer, and consequently processing the specimen routinely, which may result in an extended cold ischemic time. This delay in fixation along with insufficient formalin fixation can yield false negatives on ER/PR IHC in breast cancers and HER2 FISH in breast, gastric, and esophageal cancers, which could restrict the use of hormone therapies, such as tamoxifen and aromatase inhibitors for hormone receptor-positive (HR+) cancers, or trastuzumab for HER2+ cancers. I cannot overemphasize the importance of familiarizing yourself with clinical history and communicating case specifics while you act as a mediator between clinician and pathologist.

Whether the clinical history impacts the pre-analytical phase, such as specimen collection (limiting cold ischemic time or collecting additional needle passes for ancillary studies) or the analytical phase, as such processing (formalin fixation) and diagnosis (selecting an appropriate immunoprofile), we must remain vigilant and proactive in laboratory medicine. In this case, knowing the patient’s clinical history was of the utmost significance as it helped to reduce the number of immunostains and ancillary studies necessary to make the diagnosis. Using morphologic criteria in tandem with the patient’s clinical history narrowed the differential diagnoses to just two possible types of cancer, presented below.

A 59 year old male patient presented to the emergency room after an automobile accident. On imaging, the X-ray and CT scan identified a left humerus mass and fracture, and bloodwork was performed. His medical record was sparse and uneventful with no recent visits or encounters. To build a more comprehensive wellness profile and prepare for surgery, he was also offered a one-time screening for Hepatitis C, as an adult who was born between 1945 and 1965.

The left humerus mass was biopsied via CT-scan guidance and two passes were obtained. The Diff-Quik stained smears demonstrate large polygonal cells, some with abundant, granular cytoplasm and some isolated cells with naked nuclei. Vessels also appear to traverse some of the cell groups.

Images 1-2: Bone, Humerus, Left, CT-guided FNA. Diff-Quik-stained smears.

The Pap-stained smears also demonstrate polygonal cells with granular cytoplasm, nuclei with coarse chromatin, and prominent nucleoli. An interesting feature frequently identified in this case is the intranuclear inclusions, and in hindsight, a focus on these may have further reduced the number of immunostains performed.

Images 3-5: Bone, Humerus, Left, CT-guided FNA. Pap-stained smears.

The H&E-stained cell block sections show trabeculae with endothelial wrapping around the cell cords. While renal cell carcinoma was listed as a differential diagnosis due to its telltale oncocytic cytoplasm and vascularity, hepatocellular carcinoma was favored.

Images 6-7: Bone, Humerus, Left, CT-guided FNA. H&E sections (6: 100x, 7: 400x).

Immunostains were performed using proper positive and negative controls on the cell block sections, and the tumor cells show positive staining for Arginase, cam5.2, and Hepar1, while negative staining for CK7 and PAX8 (not shown).

Images 8-10: Bone, Humerus, Left, CT-guided FNA. Cell block section immunohistochemistry. 8: Arginase-positive; 9: cam5.2-positive; 10: Hepar1-positive.

Fortunately, before ordering immunostains, both our cytologist and pathologist working on the case peered into the patient’s medical record and noticed that he had recent bloodwork which demonstrated a positive Hepatitis C screening. This diagnosis was as recent as the identification of his humerus mass. Had it not been for his car accident, I can’t imagine how long he would have gone undiagnosed for both hepatitis and metastatic hepatocellular carcinoma. Incidental findings save lives, folks.

Granted, in settings of unknown primaries with widespread metastatic disease, such as carcinomatosis, an extensive workup is almost always inevitable. Narrowing down possible etiology based on information such as gender, age, and environmental or occupational exposure can help, but that doesn’t always yield a definitive answer as time- or cost-effectively as possible. In this case, that one clue of untreated Hepatitis C was all the cytopathology team needed. A rarity, sure, but as we are asked to do more personalized tests with less material, think of the patient’s specimen as a puzzle and keep your eye out for a clue both under the microscope and behind the computer. You never know what you might find that reduces errors and unnecessary testing while efficiently leading to a definitive diagnosis.

Peritoneal Problems

A 74 year old male patient with an extensive cardiac history initially presented to the ER with black stool, warranting a CT scan, upper endoscopy, and colonoscopy, identifying a large, obstructive mass in the colon, smaller, yet unresectable polyps, and subcentimeter liver lesions and lung nodules. The colonic mass was biopsied, consistent with adenocarcinoma; however, the liver lesions were too small to characterize. One month after the onset of symptoms, a right hemicolectomy was performed, and the pathology was signed out as moderately differentiated adenocarcinoma, microsatellite stable, with evidence of lymphovascular and perineural invasion, placing the patient’s stage at IIA (pT3, pN0, cM0). Through shared decision-making, the medical oncologist and patient elected for surveillance due to multiple comorbidities. Forgoing adjuvant therapy, the patient was discharged to physical therapy/rehabilitation. The patient returned for imaging 4 months after his hemicolectomy, demonstrating an enlargement in one of the liver lesions, but then, the patient was lost to follow-up for 20 months.

The patient reestablished care and surveillance imaging, which demonstrated a hypodense liver lesion (in a background of poorly visualized subcentimeter liver lesions), a nonocclusive thrombus in the right portal vein, a heterogenous enhancement of the left portal vein (suggestive of an underlying tumor thrombus), and an 8 cm heterogenous right adrenal mass. Based on the most recent CT scan, the differential diagnoses of the adrenal mass include metastatic disease or a primary adrenal lesion including adrenal cortical carcinoma or pheochromocytoma (for which biochemical analysis should be performed before attempting a biopsy). Extensive peritoneal lymphadenopathy was visualized as well. The area of the right hemicolectomy, however, did not show evidence of recurrence. After biochemical evaluation for metanephrines ruled out a pheochromocytoma, the patient underwent a CT scan-guided adrenal FNA and core biopsy.

The Diff-Quik smear assessed at the time of biopsy revealed a highly cellular specimen, some cells with bare nuclei, enlarged nuclei, and some pseudoglandular structures.

Images 1-2: Adrenal Gland, Right, Fine Needle Aspiration. 1-2: DQ-stained smears

Telepathology confirmed an adequate sample of tumor cells present, and core biopsies were obtained.

The following morning, the pap-stained smears and H&E cell block sections were screened. The cells appeared polygonal with a high N/C ratio and prominent macronucleoli. Cell arrangements formed thickened trabeculae. However, the cytoplasm is more granular than the lipid-rich cytoplasm seen in an adrenal cortical carcinoma. The H&E cell block sections depicted a beautiful trabecular pattern with endothelial cells wrapping the periphery.

Images 3-6: Adrenal Gland, Right, Fine Needle Aspiration. 3-4: Pap-stained smear; 5-6: H&E Cell Block sections.

The preliminary morphology was interpreted as carcinoma, and both cytotechnologist (or cytologist, as we now prefer to be called) and pathologist suggesting features of adrenal cortical carcinoma; however, the IHC markers proved otherwise!

Images 7-9: Adrenal Gland, Right, Fine Needle Aspiration, IHC Cell Block Sections. 7:HepPar1+; 8: Arginase+; 9: pCEA (canalicular pattern)+.

Other differential diagnoses considered renal cell carcinoma and pheochromocytoma (to be safe). The IHC profile ruled out adrenal cortical carcinoma as the cells of interest were negative for inhibin, calretinin, and Melan A. Negative PAX-8, EMA, AE1/AE3, and vimentin staining ruled out renal cell carcinoma, and negative chromogranin, synaptophysin, GATA-3, vimentin, and S100 staining enabled us to safely say that a pheochromocytoma was out of the equation as well. Positive staining for HepPar1, arginase, pCEA (canalicular pattern), and CAM5.2 supported the unlikely diagnosis of metastatic hepatocellular carcinoma (HCC).

This diagnosis placed the patient at Stage IV HCC. It came to light that the patient has a remote history of hepatitis and a high-risk history of drinking, contributing to a poor prognosis. Due to the patient’s condition, they held off on HCV antiviral therapy and decided to observing viral load through regular blood work. The patient and clinician discussed the risks and benefits along with alternatives of systemic therapy, as his multiple comorbidities still pose a significant risk. Immunotherapy was determined to be the best option to delay the progression of his cancer and maintain quality of life.

-Taryn Waraksa, MS, SCT(ASCP)^CM, CT(IAC), has worked as a cytotechnologist at Fox Chase Cancer Center, in Philadelphia, Pennsylvania, since earning her master’s degree from Thomas Jefferson University in 2014. She is an ASCP board-certified Specialist in Cytotechnology with an additional certification by the International Academy of Cytology (IAC). She is also a 2020 ASCP 40 Under Forty Honoree.

E(cto)pic Metastasis

A 72 year old female originally presented with lung carcinoid and bilateral renal masses. The patient’s left kidney biopsy demonstrated ectopic thyroid parenchyma by an outside institution. Her thyroid function tests were unremarkable, she had no known previous head and neck radiation, and to the best of her knowledge, there was no family history of thyroid cancer. She underwent FDG PET imaging, which showed increased bilateral uptake in the neck (thyroid and lymph nodes), and an avid right posterior renal mass. Otherwise, her scan was relatively clear. Her left renal mass was resected and demonstrated thyroid parenchyma, but the differential diagnoses included thyroid heterotopia and metastatic well-differentiated thyroid carcinoma.

FNA and core biopsy were then obtained from the right upper quadrant of the kidney. The findings are depicted below.

Images 1-6: Kidney, Right, Fine Needle Aspiration. 1: Pap-stained smear; 2: DQ-stained smear; 3: H&E Cell Block section; 4: TTF-1+; 5: Thyroglobulin +; 6: CK7+.

The FNA was signed out as “Atypical thyroid tissue present.” Immunohistochemical stains demonstrated positive staining for CK7, vimentin (partial), TTF-1, thyroglobulin, and PAX-8 (partial), and negative staining for RCC, Napsin A, synaptophysin, and chromogranin. While these immunostains suggest thyroid-type tissue, morphology was most worrisome for metastatic thyroid carcinoma. The chromatin presented as hypochromatic and powdery, nuclear grooves and pseudoinclusions were present, and the nuclei were enlarged with irregular membranes. However, the scant material present precluded a definitive diagnosis.

Images 7-8: Kidney, Right, Core Biopsy. 7, H&E section 100X; 8, H&E section 400X.

The core biopsy suggested benign-appearing thyroid tissue similar to that seen in the left kidney, however, the surgical pathologist diagnosed the material as metastatic thyroid carcinoma.

A thyroid FNA was obtained from one of the patient’s multiple right-lobed thyroid nodules consistent with TI-RADS category 5 the next day. This was diagnosed as atypia of underdetermined significance due to scant cellularity.

Images 9-10: Thyroid, Right Lobe, Fine Needle Aspiration. 9: DQ-stained smear; 10: Pap-stained smear.

The right renal mass was resected after molecular profiling was performed on the left renal mass tissue. Mutation Detection by Next Generation Sequencing demonstrated a tumor mutation burden of 3.6Muts/Mb and identified mutations in the PRKDC, PTEN, and KRAS genes. Two kidney tumors were identified in the right kidney (one measuring 8.0 cm and the other 4.5 cm), both diagnosed as metastatic thyroid carcinoma with papillary features.

Images 11-12: Kidney, Right, Resection. 11, H&E section 40X; 12, H&E section 400X.

The thyroid was then resected, and pathologic findings were consistent with invasive follicular carcinoma with extensive angioinvasion to 4 or more vessels. While renal metastases are rare, the high affinity for angioinvasion makes the kidney a prime metastasis site due to its vascular-rich tissue. The patient was prescribed a low iodine diet and Thyrogen-stimulated radioiodine ablation to remove any remaining thyroid tissue or micrometastases and enhance the sensitivity of thyroglobulin as a tumor marker for surveillance purposes. While thyroid cancer (papillary and follicular types) is typically considered “the best cancer to have” due its slow growth and low-risk of widespread malignancy, it doesn’t mean that it won’t metastasize, even to a distant organ that you normally wouldn’t suspect. Great caution must be taken to ensure that lumps, bumps, and swallowing issues are addressed at annual physicals to catch a low-risk cancer before it has the opportunity to become an epic metastasis.

By the Book

One of my favorite parts of being a cytotechnologist is the delight of having cytology students rotate through our institution as a practicum site. The pandemic caused a clinical rotation hiatus for the safety of both our staff and students, but thanks to widespread healthcare vaccination, we were able to bring in some fresh minds to experience the variety of interesting cases we enjoy every day. I think what I love most about having students here is reminiscing of when I was in their shoes seven years ago. I remember going into my rotations using nothing but morphologic criteria I memorized from lecture and labs. My clinicals served as a rude awakening that we rarely see any textbook perfect cases. Cancer is like a shape-shifter – one melanoma looks entirely different than another. Two lung squamous cell carcinomas from the right upper lobes from two different patients could look entirely different. The unique variation within and between cancer types is what makes this field so beautifully fascinating. The first time a cytotechnology student shows me a case, tells me their thoughts, works through the criteria, and lists the differentials, I look up and say, “nothing is quite by the book.” How often we fall into a routine of relying on criteria, closing our minds to certain diagnoses because it doesn’t quite look like the clinical impression. When the pathologic and clinical impressions divide, more diagnostic tests are performed, CPT codes fill our billing tab, and we start to panic. “It’s supposed to be adenocarcinoma, so why doesn’t it look like adenocarcinoma?!?

A few weeks ago, the lab received a left pleural fluid from a patient who presented with a history of small cell cervical cancer. I remember learning about this in my first semester of grad school – how rare a finding of small cell carcinoma is, accounting for less than 5% of cervical cancers. It essentially mimics small cell carcinoma of the lung and other neuroendocrine carcinomas, where you should be able to identify the telltale salt-and-pepper chromatin, nuclear molding, scant cytoplasm, loosely cohesive or isolated, necrosis, usually an absence of nucleoli, a high proliferation index with mitotic figures, etc. It’s an aggressive disease to say the least, just like its lung counterpart. When this cancer metastasizes, it takes its same characteristics with it, spreading rapidly without care.

The first step in processing a fluid is to prepare a fresh, air-dried, Diff-Quik-stained cytospin to triage the specimen and decide whether the specimen should be processed routinely or hand-prepped and stained with overtly positive fluids to prevent cross-contamination. There was one cluster identified on the Diff-Quik preparation, but compared to the background of mesothelial and inflammatory cells, the tumor content was insufficient to push it up to hand-processing. The bluish cytoplasm caught my attention as a feature of neuroendocrine tumors AND lymphomas, but the nuclear molding had me favoring neuroendocrine.

Image 1. Pleural fluid, left. DQ-stained cytospin.

That afternoon, I examined the pap-stained smears and SurePath liquid-based preparation, identifying similar cells of interest. However, despite the presence of nuclear molding and scant cytoplasm, the nuclei presented with prominent nucleoli. An interesting feature, to say the least.

Images 2-5. Pleural fluid, left. 2-3, Pap-stained smears (2, lightened to highlight nucleoli); 4-5, Pap-stained SurePath liquid-based preparation.

The following morning, I screened the cell block slides and came across molded groups of cells (appearing as a garden aerial view). Still the prominent nucleoli baffled me, and I thought, “Why doesn’t this look like a classic small cell carcinoma? They clinical history even included known lung mets from the patient’s small cell cervical cancer!”

Images 6 and 7: pleural fluid, left. 6, H&E cell block section 100X; 7, H&E cell block section 400X.

When I sent the case for review by the pathologist, I wrote up a diagnosis of Positive for Malignant Cells; Carcinoma, small cell? Recommend correlation with IHC.” My attending was just as intrigued. She ordered a thorough panel of immunohistochemistry stains based on the morphologic findings.

Images 8-11. Pleural fluid, left. 8, synaptophysin+; 9, CD56+; 10, TTF-1+; 11, BerEP4+.

The tumor cells are positive for synaptophysin, CD56, TTF-1, and BerEP4, focally positive for CK7 and chromogranin (not shown), and negative for calretinin, PAX-8, and p40 (also not shown). The findings support the diagnosis of metastatic high grade carcinoma with neuroendocrine differentiation.

While the stains support a diagnosis of small cell carcinoma, the morphologic diagnosis was mildly questionable. I went back to the patient’s record to see what we may have missed in the clinical history. It turns out the patient initially presented with Stage IB2 HPV+, moderately-differentiated cervical adenocarcinoma in 2020. After completing brachytherapy and one cycle of chemotherapy, but could not tolerate additional treatments due to leukopenia and elevated LFTs. Shortly thereafter the patient complained of abdominal pain and a liver mass and bulky lymphadenopathy were identified on imaging. An FNA of a supraclavicular lymph node confirmed not only metastasis of the patient’s cervical cancer, but discovered a small cell/neuroendocrine transformation. And this is why proper documentation of clinical history is so important to pathologists and laboratory professionals. In one of my earlier posts, I preached that cancer doesn’t discriminate; so why should we? Keeping an open mind is paramount to both succeeding in and enjoying the field of cytopathology. If it looks like a duck, and it walks like a duck, it might actually have transformed into a goose.

Cytology Case Study: Strike a Chord

Every FNA ROSE attended where the patient is conscious and attentive can be tricky to navigate. You have to remain cognizant of your word choice, your demeanor, and the delivery of your adequacy statement to the clinician. The patient is already in a heightened state of awareness because he or she is about to be probed with a needle (or six!) for a test that is likely to rule out a benign or malignant process. I prefer to go into my biopsies with some sort of clinical picture and as many details as I can retain – is there a previous history of cancer? Where is the lesion located? Is it a single mass or are there multiple lesions? What does the radiologic imaging suggest? Are there any elevated serum tumor markers? I need to be able to walk the walk and talk the talk. However, there are rare instances when cytotechs are asked to rush down to an unscheduled add-on biopsy where we have yet to research the impression documented in the patient’s medical record. In those situations, I ask the clinician (typically an interventional radiologist) all the questions I can think of while still emulating some form of confidence to the patient.

I entered the procedure room and greeted the radiologist, radiology fellow, tech, nurse, and the patient, a 57-year-old male who was prone and alert on the table. I jotted down notes during the timeout and pulled the radiologist aside to ask, “does the patient have a history of cancer?” In this case, the answer was “they have a soft tissue tumor in the left gluteus, which is what we’re biopsying.” “Alright, let’s get those differentials rolling – sarcoma; after my hibernoma experience – a lipomatous tumor; or could it be a carcinoma (because yes, I’ve seen a lung adenocarcinoma metastasize to the gluteal muscle before)? Hmm… what else? What other mesenchymal tumors could originate here… or metastasize here?” My brainstorming balloon was popped by the radiologist asking if I was ready for the first needle pass. I replied, “Yes, of course!” I glance over at the patient and smile, trying to assure him AND myself that I’ll be able to give him a definitive answer to his puzzle.

Here’s what I visualized under the microscope after I stained the first air-dried smear in our Diff-Quik solutions.

Images 1-2. Left gluteal FNA, DQ-stained smears.

My inner monologue became: “Well, it’s not a sarcoma or a carcinoma. It doesn’t look malignant. Not quite a hibernoma. What is with that myxoid matrix? It’s not mucinous or serous, so… what is it…? It’s granular! Wait. Those nuclei. They’re so… what’s the word? It’s definitely representative of the lesion. Regardless, it’s adequate!” I turned away from my microscope to face the team – “The sample is adequate. May I have a few more passes for my cell block, and will you collect core biopsies, too? “Yes and yes,” the radiologist replied. I smiled again at the patient, and he mouthed, “thank you.” “Phew, mission accomplished,” I thought. “Now what the heck are those hallmark cells called mixed in with a majority of epithelioid cells arranged in chords?”

I climb the stairs up to the lab and do a quick Google search. “DUH! Physaliphorous cells!” These cells have a distinct feature where the nucleus is centrally located but is also scalloped by cytoplasmic vacuoles. There weren’t as many physaliphorous (physaliferous) cells as I had hoped to appreciate. Some of the cells looked lipoblastic in nature with larger vacuoles displacing the nuclei to the periphery, almost signet ring in nature, many were cuboidal. But that was it… those cells! Now, imagine the scene in Finding Nemo where Nemo struggles to tell his classmates he lives in an anemone. That was my garbled attempt at pronouncing “physaliphorous” to the attending pathologist when sharing my interpretation. She looked at me like I was saying anything other than the word I was trying to reproduce. I cannot blame her; I still turn beet-red at the memory. But I was convinced that a chordoma was the tumor I presented to her.

After I processed my FNA, I examined the patient’s electronic health record to see if he had any previously biopsied neoplasms on file, and much to my surprise, the patient was diagnosed with a primary chordoma of the sacrum and treated with en bloc resection and radiation in 2013. Mutation analysis was performed on the resection of this chordoma, which exhibited a homozygous loss of CDK2NA (p16). The patient had one recurrence at an outside facility in 2015 and transferred his care to our institution for follow-up. Now, the patient presented with this gluteal metastasis and soon thereafter, a paraspinal metastasis. As the patient’s chordoma did not completely respond to radiation, the clinical care team turned to the tyrosine kinase inhibitor, Gleevec, which was discontinued due to disease progression. The patient’s regimen then went on to include sunitinib, which was also discontinued due to disease progression, palbociclib, then nivolumab, followed by radiation to the thoracic spine, sorafenib, and now is on a clinical trial for patients with advanced refractory cancers.

When I turned in my Diff-Quik & Pap-stained slides and the cell block H&E sections with a diagnosis of chordoma the next day, the attending cytopathologist paged through one of our cytology texts to a tidbit on chordomas before signing out the case. She reviewed the section with me. Other than the unique physaliphorous cells, it turns out a diagnosis of chordoma is fairly rare, as it is the only malignancy derived from the notochord, typically occurring at either end of the axial skeleton.¹ Metastasis of these tumors is also rare, so this case of widespread metastatic disease was even more intriguing to me.

Images 3-8. Left gluteal FNA . Images 3-5, Pap-stained smears; 6-8, H&E cell block sections.

References

Cibas, E. S., & Ducatman, B. S. (2009). Cytology: Diagnostic Principles and Clinical Correlates, Expert Consult – Online and Print (3rd ed.). Saunders.

Beggars CAN Be Choosers

There is a fine line between obtaining enough cellular material for every ancillary study in the book and risking harm to the patient. So how do we ensure that the patient remains safe, but doesn’t need to come back for a second biopsy due to insufficient material?

Hi! I’m Taryn, a Specialist in Cytotechnology at Fox Chase Cancer Center and a medical laboratory professional who thrives on patient advocacy. Welcome to my first post for Lablogatory! Each month, I’d like to share a story of how the middleman/woman cytotechnologist becomes the biggest campaigner for the patient. Typically, I’ll be posting case studies of rare tumors and how we arrived at the diagnosis, but I’ll start with how to guarantee that we have ample material to provide a comprehensive result for both the patient and clinicians.

It’s a fight, to say the least. With personalized medicine at the forefront of our cancer center’s mission, we need ALL of the material for any and every ancillary test one can think of, from immunohistochemistry to flow cytometry to molecular diagnostics. That sounds like a lot because it is. From my experience, many clinicians feel that just because cytotechnologists can make a satisfactory adequacy statement on a Rapid On-Site Assessment (ROSE) of a Fine Needle Aspiration Biopsy (FNA), and the pathologists can make a definitive diagnosis based on cytomorphology alone, that means they have obtained sufficient material. For years, that was a valid thought. But now that we have taken various leaps from diagnostic to prognostic and now theranostic approaches, “enough” for cytomorphology is nowhere near “enough” for the patient’s clinical outlook.

As a cytotechnologist present on FNA’s, I have been called “greedy” and a “beggar” by clinicians on more than one occasion. No hard feelings, I promise. As long as the anatomical location of the biopsy does not pose more risk than reward, rest assured, I’m going for the gold medal. Starting out, I obtain one or two fine needle aspiration passes from the radiologist, pulmonologist, gastroenterologist, etc., and from each pass, I prepare one smear to be stained on-site via Diff-Quik (Modified Wright-Giemsa stain) and the mirror image smear fixed in 95% ethanol to be Papanicolaou stained later in the lab. The residual material in the needle is rinsed in Hank’s Balanced Salt Solution (A.K.A. Gatorade for cells) and later spun down into a pellet for a Formalin-Fixed Paraffin-Embedded (FFPE) Cell Block. I look at the Diff-Quik stained smears under the microscope and tell the clinician if the material I have is adequate, scant, or inadequate. This is where it gets interesting.

Clinician: “Adequate. So, we’re done? Okay.”
Cytotechnologist: “The smears are adequate, but I need more material for the Cell Block. Can I have two more passes? And a core biopsy, as requested on the presentation state.”
Clinician: “But you have enough. We already know the patient has lung cancer. You don’t need anymore. I’ll give you a core biopsy, but no more fine needles.”
Cytotechnologist: “I need at least two more needles. The core biopsy material will be saved for molecular. The ordering physician wants to know if the patient’s EGFR-mutated tumor also carries a T790M mutation to see if they are eligible for this therapy. But I also need additional needle passes for the Cell Block to prove that the immunohistochemical profile is the same as the original material. If there is a small cell carcinoma component in the metastasis, that changes things.”
Clinician: “Fine. Pathology is so greedy.”

Okay, so we have definitely progressed into a new era. Many newly trained clinicians understand the need for ample material, but this conversation still occurs on a daily basis. Don’t get me wrong, the veteran clinicians (from my snippet) are remarkable. They can find a needle in a haystack, hit a moving target time and time again, and provide me with a perfect tumor-rich sample. But alas, in trying to educate and advocate, I admit- I do come off as a beggar. The key in our ROSE role is to not back down though. Cytotechnologists remain strong in their convictions, fighting for the patient, so that not only do we have enough cellular material for all of the necessary ancillary studies the first time around, but that hopefully the first time around is the ONLY time around.

We’ll chat soon!

Taryn Waraksa, MS, SCT(ASCP)^CM, CT(IAC), has worked as a cytotechnologist at Fox Chase Cancer Center, in Philadelphia, Pennsylvania, since earning her master’s degree from Thomas Jefferson University in 2014. She is an ASCP board-certified Specialist in Cytotechnology with an additional certification by the International Academy of Cytology (IAC). She is also a 2020 ASCP 40 Under Forty Honoree.

A Trainee Abroad: One Cytopathology Fellow’s Experience at a Teaching Hospital in Rwanda

The University Teaching Hospital of Kigali (CHUK) is the largest hospital in its District of Nyarugenge and the biggest national referral hospital in the country of Rwanda, with a 565 hospital bed capacity and 6 operating theaters. It is located in the heart of the capital of the country, Kigali, contributing to its easy accessibility by patients. Rwanda is a country of over 12.5 million people, with an estimated 70.2% of the population living in a rural setting. Per the World Bank, there is an estimated 1 physician per 10,000 people in-country. The government of Rwanda is focused on elevating the country from a low-income developing nation to a middle-income country with a robust health sector capable of ensuring a healthy people with adequate healthcare access. It provides universal healthcare, at a small cost, to all Rwandan citizens who aren’t provided health insurance through employment. In Rwanda there are a total of 14 practicing pathologists, which equates to approximately 1.1 pathologists per million people in the country. In contrast, within the United States there are an estimated 60 pathologists per million people. CHUK offers an array of outpatient, inpatient, surgical, and diagnostic medical services. Inpatient and outpatient services include surgery, accident & emergency, internal medicine, mental health, anesthesiology & critical care, gynecology, pediatrics, maternal & neonatology, ear/nose/throat, ophthalmology, neurosurgery, pediatric surgery, urology, nephrology, dialysis, oncology, and dermatology. Surgical services include general surgery, general pediatric surgery, neurosurgery, orthopaedics, ophthalmology, ear/nose/throat, and obstetrics/gynecology. Diagnostic services include ultrasound, digital x-ray, CT scan, and anatomic and clinical pathology services. In its current state, the hospital has a total of 18 divisions.

There are two facets to the pathology laboratory at CHUK: the Anatomic Pathology (AP) and the Clinical Pathology (CP) laboratories. Within the AP laboratory, also known as the histopathology laboratory, all surgical specimens are grossly examined by a pathology resident and/or pathologist, prepared by a pathology resident for processing, and processed by laboratory technicians into formalin-fixed paraffin-embedded tissue placed onto glass slides. These glass slides are then reviewed by both the pathology residents and the pathologists in order to render a diagnosis, which is communicated to the clinician in order to help direct appropriate patient management. Specimens reviewed at CHUK are predominantly “in-house” specimens generated by the surgeons and clinicians functioning within the walls of the institution. “Referral” specimens are a rarity and generally consist of small biopsies. Cytopathology specimens are also processed within the AP laboratory and include a mixture of fine needle aspiration (FNA) specimens, obtained by pathology residents via superficial FNA, as well as exfoliative cytology specimens such as effusions and urines collected by “in-house” clinicians. Cervical screening conventional pap smears are a rarity. Within the AP laboratory, Diff-Quik, Papanicolaou, and hematoxylin & eosin (H&E) staining was available for slides, as well as a limited panel of special stains: PAS-D, auramine, and a modified acid-fast stain. No immunohistochemistry was available on-site, though cases could be sent for free to nearby Butaro Hospital for IHC or consultation via digital slide scanning.

Regarding my experience at CHUK, I departed the United States on a Saturday evening and reached Kigali, Rwanda by 1AM the following Monday morning. On my first day at CHUK, I was introduced to the 5 anatomic pathology staff, 9 anatomic pathology residents, and the single visiting pathologist serving as a laboratory inspector conducting a mock inspection/assessment. I was given a tour of the pathology facilities as well as the entire hospital system.

There were two aspects to my primary job at CHUK: teaching the residents cytopathology and microscopic review of all live cytopathology cases received in the laboratory. Regarding resident education, there were four ways in which I interacted with the residents during my time to facilitate cytopathology education: lectures, multi-headed microscope unknown slide sessions (unknown case conference where I provided the residents with cases they had never seen before), multi-headed microscope “stump the chump” unknown slide sessions (where the residents presented me with unknown cases I had never seen before), and interactive practicals where we performed various hands-on aspects of cytopathology and general pathology practice.

In respect to lectures, I delivered a total of eight 1.5 hour powerpoint-based lectures covering the following topics: breast cytology, thyroid cytology, lymph node cytology, salivary gland cytology, urine cytology, effusion cytology, peritoneal washing cytology, and frozen section pathology (frozen section lecture presented as a combined effort with Dr. Raina Flores). For unknown slide sessions in which I presented cases to the residents, we had 6 sessions covering the following topics: breast, thyroid, salivary gland, urine, conventional pap, and cerebrospinal fluid. We completed a total of 5 “stump the chump” sessions, where residents gave me slides that I had never seen before and we discussed each case and its work-up as well as its associated differential diagnosis or final pathologic diagnosis at the multi-headed microscope. Topics covered included: breast, thyroid, salivary gland, lymph node, and effusions. Finally, with the assistance of “in-house” pathologists, I helped conduct 2 hands-on practicals with the residents: the first regarding fine needle aspiration technique and slide smearing technique (with Dr. Claire Nadyisaba) and the second regarding performance of frozen section intraoperative consultations using Leica CM1850 cryostats and cow liver (with Dr. Raina Flores).

The second of my duties, live cytopathology case review, was also performed at the multi-headed microscope with the residents each afternoon. On a given day, we would typically receive somewhere between 1 and 4 FNA consultations for which the residents would go to FNA clinic and perform the procedure. The laboratory also received various aspirated and exfoliative cytology specimens, such as pleural effusion and ascites fluids, from clinicians within the hospital system. In total, we reviewed 51 cytopathology cases together at the microscope. 27.5% were neoplastic, with 7.8% being malignant and 2% being lymphoma. 56.8% of cases were negative for malignancy, with 21.5% being inflammatory/infectious. In total, 9.8% of cases were interpreted as “atypical” and 5.9% of cases were non-diagnostic. Of the 51 cases, 21 (41.2%) were FNA consultations that I attended and the resident performed.

On my final day of work, I provided the residents with a 41-page cytology knowledge assessment (in PDF format) to complete at their leisure. This test covered the following topics: cervical and vaginal cytology (19 questions), urine and bladder cytology (11 questions), effusion cytology and peritoneal washings (13 questions), cerebrospinal fluid cytology (12 questions), breast cytology (8 questions), thyroid cytology (17 questions), salivary gland cytology (13 questions), and lymph node cytology (11 questions). Within the document, an answer key with associated detailed explanations was provided so it could serve as a learning aid/study guide for the trainees. On my last workday, the residents were asked to evaluate their experience with the Cytopathology Module/Course. A total of 7 of 9 residents completed the evaluation. Regarding preparation and organization of different topics, all residents found the quality of the powerpoints to be “very good” or “excellent”. The quality of the practical sessions was rated as “good,” “very good” or “excellent by all residents and the entire module was given an overall rating of “very good” or “excellent” by all of the residents. The majority of residents felt their time was used effectively during this module and that the venues for theoretical and practical learning were appropriate. In the free-text areas for additional comments, suggestions for improvement included a longer duration (at least 4 weeks) of the module, more hands-on practical time, the opportunity for residents to present information, and more microscopy sessions. For additional topics to be covered, respiratory cytology was suggested. In overarching comments regarding their module experience, the residents felt the module was well-prepared, the teaching sessions were well-organized, and that the course was interesting and helpful.

Finally, though not within the confines of my assigned “duties”, I also spent a portion of each day acting as “consultant” to the on-site pathologists for challenging surgical pathology cases, offering opinions as able for various lesions that were challenging to classify on H&E morphology alone. I also served as a “second reviewer” for new malignant diagnoses being rendered in the laboratory, offering my name to be included in the report as a board certified pathologist who has laid eyes on the case and agrees with the interpretation. Examples of some interesting surgical pathology cases I saw in “consultation” included Wilms tumor (nephroblastoma), cystic partially differentiated nephroblastoma (CPDN), pleomorphic xanthoastrocytoma (PXA), sinonasal undifferentiated carcinoma, basaloid moderately-differentiated carcinoma of the uterine cervix, high-grade large cell lymphoma of the cervical lymph node, high-grade squamous intraepithelial lesion of the vulva arising within a condyloma acuminatum, and low-grade papillary urothelial carcinoma of the bladder. I also attend a single Tumor Board Multidisciplinary Conference with two residents and 1 staff pathologist in which a resident presented a case of mucinous moderately-differentiated adenocarcinoma of the colon transmurally invading adjacent ileum. It was interesting to hear the clinicians, pathologists, and radiologists interact in addressing quality of care, efficiency of care, and clinical decision-making. The time of initial presentation to the time of surgery was greater than 1 year for this patient.

My time spent at CHUK in Kigali, Rwanda was an invaluable experience. The work setting granted me the opportunity to expand my role as an academic educator. I was offered the opportunity to present as many lectures as possible to the resident trainees, participate as the leader of multi-headed microscope slide sessions, serve as a spearheading physician in laboratory services expansion efforts, and work as an ‘attending’ physician overseeing trainees’ performance of FNAs. It was an experience that demanded personal growth, via the assumption of roles that I am not privy to as a post-graduate medical education trainee in the United States. Additionally, I was exposed to a cytopathology and surgical pathology workload for a patient population quite dissimilar from the community I am used to serving. With limited ancillary testing capabilities, I returned to a more “pure” form of rendering pathologic diagnoses, based on H&E morphology alone rather than on the synthesis of cyto- and/or histomorphologic appearance coupled with various ancillary diagnostic testing data points. In conclusion, this was an experience that expanded my understanding of the ways in which I can be useful as a board certified anatomic and clinical pathologist interested in incorporating medical mission work into my clinical practice. Beyond arriving in countries without expansive pathology laboratory systems and simply doing the work, I can also pursue opportunities where I can help educate and shape burgeoning in-country pathologists who will then go on to have productive, hopefully decades-long careers in their country, serving their countrymen. This trip certainly expanded my understanding of the role of a “visiting” pathologist. This experience was made possible by the ASCP Trainee Global Health Fellowship Award. Thank you so much to the ASCP, Dr. Dan Milner, Alpa Pandya, and the CHUK pathology department for helping to facilitate this opportunity!

Image 1. Dinner with CHUK pathologists and pathology residents

Image 2. Frozen section training with CHUK pathology residents

Image 3. CHUK laboratory medicine building

Image 6. Small “downtown” area near CHUK hosptial–Kwibuka (“to remember”) memorial in remembrance of the 25th anniversary of the Rwandan genocide.

Image 8. Ferry ride to various neighborhoods in Kigali

-Kelsey McHugh, MD is a board certified anatomic and clinical pathologist, with cytopathology subspecialty certification, who is currently completing gastrointestinal, hepatic, and pancreatobiliary pathology subspecialty training. She anticipates graduating from the Cleveland Clinic Gastrointestinal, Hepatic, and Pancreatobiliary Pathology Fellowship in June 2020, after which she will remain at the Cleveland Clinic as a staff pathologist beginning July 2020.