An ASCP Volunteer’s Experience Abroad

I volunteered in April 2019 in Tanzania at the Kilimanjaro Christian Medical Center. I was there specifically to teach breast mastectomy grossing. There are two pathologists at KCMC, Dr. Mremi and Dr. Patrick, but finding time in their schedule to work with them proved to be the biggest challenge. The pathologists have many responsibilities outside of just looking at slides. Dr. Alex Mremi is the head of the department, but he also teaches at the medical school and meets with medical students. The pathologists at KCMC perform autopsies, including the forensic autopsies that would normally be sent to a medical examiner or coroner’s office in the United States. Dr. Mremi was pulled away one day to do an autopsy and two other days to go to court to discuss autopsy findings. One of the days Dr. Mremi also performed an FNA, where he was not only preparing the slides, but procuring the specimen from the patient himself.

In the end I was able to go over one mastectomy case with each pathologist, but I had hoped to discuss my case study examples and talk to them about the differences in our grossing techniques in greater detail. When the pathologists were busy I would go over grossing techniques of the less complex specimens with the lab aides that perform grossing. Unfortunately the lab aides have responsibilities as accessioner, histotech, grossing aide, transcriptionist, etc. They do it all, so it was equally difficult to find time in their busy schedule. In addition to scheduling conflicts, there was also the issue of ventilation in the gross room. Because there is a window fan, but not proper ventilation, whoever is grossing could only be in the gross room for a limited amount of time before formalin exposure would be too much. I did bring a formalin 3m mask that was donated by a colleague of mine with some replacement cartridges that I hope they will implement into their routine.

In retrospect I wish I had known how difficult it would be to schedule my grossing time with both the pathologists and the lab aides. It takes a forceful and persistent personality to wrangle people into the gross room when they are bogged down with their other work. I wish I had known about this blog before my trip to Tanzania because this seems to have been previously stated by PAs. I would also recommend that the PA make sure to have all their transportation arrangements and initial appointments at the hospital set up in advance because you will essentially be dropped in a place with no Wi-Fi. I made sure to arrange all of this with the help of Alpa Pandya, Dr. Milner’s assistant, who was incredibly helpful. If you are able to exchange money in advance or schedule a trip to the bank with your airport driver this will be very helpful. The day I arrived was a Sunday so banks were closed. It was somewhat of a challenge to find a restaurant or local transportation that would take US dollars. I would recommend getting your visa before your trip because this may prove difficult to accomplish at the airport upon arrival. Be sure to get all the recommended vaccines and anti-malarial medicine if necessary in the area you are travelling. I was very surprised to see no mosquitos at all during my entire trip and find out that malaria is nearly eradicated in the Kilimanjaro region. I also had my clothing sprayed with an anti-bug spray that may have helped keep flies away from me. I would recommend people learn basic phrases (hello, thank you, please, etc.) in the language of the country they are visiting to be more respectful of the local people. Language apps such as Duolingo or Babel are a great help.

I recommend that if a PA is volunteering in a low resourced setting they find out exactly what would be most beneficial to the pathology department in that setting. Since my trip was more focused on breast mastectomy grossing I brought Lester, breast diagrams, templates, inking diagrams, breast protocols and procedures from my hospital, as well as multiple case examples. Some of which I laminated in advance so they could be used again and again in this setting. If I were to volunteer again I would try to set up a more concrete schedule in advance with exact times blocked out to discuss techniques, be in the gross room or give presentations. I am incredibly grateful I got to have this experience, I only wish I was able to make more of an impact. I hope that more PAs will continue to volunteer and that pathologists will participate in the telepathology volunteer roles to free up more time for the few pathologists in these low resource environments. Thank you again to ASCP, Dr. Milner and Alpa for this opportunity!

-Faith Fletcher is a Pathologists Assistant at Henry Ford Hospital in Detroit, Michigan.

Microbiology Case Study: An 8 Year Old Male with Left Knee Pain

Case History

An 8 year old male with no significant medical history presented with left knee pain and swelling for one week. Physical examination revealed a temperature of 101.2°F and a left swollen, tender knee with reduced range of motion. A joint aspirate was performed, and synovial fluid and blood were sent for microbiological analysis.

Laboratory Findings

Synovial fluid analysis showed increased neutrophils, a nucleated cell count of 90,840 cells/cmm, and no crystals.

Blood cultures were negative. Gram smear of the joint fluid showed many neutrophils and no bacteria. Fluid culture grew convex tan-yellow colonies on blood and chocolate plates at 48 hours (Image 1). Gram smear revealed gram-negative cocci (Image 2). The organism was identified by MALDI-TOF as Aggregatibacter aphrophilus. Antibiotic susceptibility testing showed susceptibility to augmentin, ampicillin, ceftriaxone, and levofloxacin.

Image 1. Growth on anaerobic chocolate plate.
Image 2. Gram stain from anaerobic culture showing gram negative cocci.

Discussion

Aggregatibacter aphrophilus is a gram negative coccobacillus that requires 5% CO2 and grows best on blood agar. It is oxidase negative and catalase negative. It is categorized as a HACEK organism, being a cause of culture-negative endocarditis. It is considered normal oral flora, and dental procedures can be a source of infection. Aggregatibacter endocarditis can cause a positive P-ANCA and be misdiagnosed as a vasculitis. It has also been reported as causes of sacroiliitis, bartholinitis, endophthalmitis, and brain abscesses. Treatment is generally ceftriaxone for 8 weeks. Identification is by biochemical methods or MALDI-TOF. Broad range PCR (br-PCR) has also been described, which targets a highly-conserved region of 16S rDNA, and then compares the sequences to database sequences.

The patient was given cefazolin, and his temperature downtrended. He was discharged prior to results but placed on oral augmentin. After susceptibility testing, infectious disease was consulted and he was placed on ceftriaxone for 8 weeks. He continued to improve and subsequent cultures were negative.

References

  1. Ratnayake L, Olver WJ, Fardon T. Aggregatibacter aphrophilus in a patient with recurrent empyema: a case report. J Med Case Rep. 2011;5:448. Published 2011 Sep 12. doi:10.1186/1752-1947-5-448
  2. Hirano K, Tokui T, Inagaki M, Fujii T, Maze Y, Toyoshima H. Aggregatibacter aphrophilus infective endocarditis confirmed by broad-range PCR diagnosis: A case report. Int J Surg Case Rep. 2017;31:150–153. doi:10.1016/j.ijscr.2017.01.041

-Jonathan Wilcock, MD is a 1st year anatomic and clinical pathology resident at the University of Vermont Medical Center.

-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Associate Professor at the University of Vermont.

Hematopathology Case Study: A 36 Year Old Woman with an Incidental Neck Mass

Case History

A 36 year old female underwent thyroidectomy for multinodular goitre that led to the fortuitous discovery of a neck mass. The neck mass specimen submitted comprised two lymph nodes measuring 2.2 cm and 1.3 cm in the greatest dimensions, with a fleshy tan cut surface.

Biopsy Findings

H&E stained sections revealed numerous non-necrotizing granulomas effacing and replacing normal lymph node architecture. These consisted of pale epithelioid histiocytes and Langhans type of giant cells. The granulomas lacked a peripheral rim of lymphocytes. AFB and GMS stains were negative for microorganisms

Diagnosis

A diagnosis of non-necrotizing granulomatous lymphadenitis was rendered noting that in the correct clinical context the findings could represent sarcoidosis.

Discussion

Granulomatous inflammation is a special type of chronic inflammatory response characterised by the formation of discrete collections of histiocytes called granulomas. Activated histiocytes appear as epithelioid cells with round to oval nuclei, often with irregular contours and abundant granular eosinophilic cytoplasm with indistinct cell borders. They may coalesce to form multinucleated giant cells. When found in the lymph node, the reaction pattern is called granulomatous lymphadenitis. It can be caused by a variety of different conditions, and therefore, requires thorough workup to come to a conclusive diagnosis.

On the basis of presence or absence of necrosis, granulomatous lymphadenitis can be classified as necrotizing or non-necrotizing. Additionally, the presence of an abscess, usually central, indicates a suppurative lymphadenitis.

Non-necrotizing granulomatous lymphadenitis:

Sarcoidosis lymphadenitis is the prototype of non-necrotizing granulomatous lymphadenitis. It shows the presence of discrete granulomas without a peripheral rim of lymphocytes, called “naked granulomas”. The early phase shows follicular hyperplasia and sinus histiocytosis, followed by appearance of epithelioid cell nodules toward the end of this phase. The peak phase shows well-demarcated granulomas composed of epithelioid cells with scattered multinucleated giant cells observed throughout the lymph node. Granulomas may occasionally coalesce. In the late phase, increased collagen fibers result in fibrosis and hyalinization. There are no neutrophils and it is uncommon to find small foci of central necrosis. Numerous inclusions such as asteroid, Schaumann, or Hamazaki-Wesenberg bodies can be seen. In this case, we observed well-demarcated granulomas throughout the lymph node, typical of the peak phase without any caseous necrosis or suppuration.

Other causes of granulomatous lymphadenitis can be ruled out as follows.

Sarcoid-like lymphadenitis: It shows a similar pattern of non-necrotizing lymphadenitis like sarcoidosis. However, classically sarcoid like reaction shows scattered small epithelioid granulomas with sparsely arranged epithelioid cells. The border of the granulomas is usually obscure. The CD4:CD8 ratio ranges from 0.8 to 2.25 while in sarcoidosis, it is >3.5. These findings help distinguish sarcoid-like lymphadenitis from sarcoidosis.

Sarcoid-like adenitis may be seen in numerous conditions such as carcinoma, Toxoplasmosis, fungal infections, tuberculosis, immunocompromised states, pneumoconiosis etc. The fact that tuberculosis and fungal infections can present with a non-necrotizing granulomatous lymphadenitis highlights the importance of performing fungal (PAS & GMS) and AFB (Ziehl Neelson) stains in non-necrotizing lymphadenitis as well. In this case, the granulomas had distinct borders, numerous epithelioid cells, no organisms were identified on special stains, nor was there any history of immune compromise; ruling out a sarcoid-like reaction.

Berylliosis: The lymph node picture in Berylliosis is identical to that of sarcoidosis. We may even see asteroid bodies or Schaumann bodies. A diagnosis can be established by eliciting a history of chronic exposure to Beryllium. Beryllium lymphocyte proliferation test (BeLPT) is a test that measures Beryllium sensitization and is very specific for Beryllium exposure. There was no known history of exposure to Beryllium in this case.

Toxoplasmosis: A classic triad of follicular hyperplasia, small granulomas composed of epithelioid cells within and around hyperplastic follicles and, monocytoid B cell hyperplasia, is observed in toxoplasmosis lymphadenitis. This case did not show follicular hyperplasia, ruling out toxoplasmosis.

Necrotizing granulomatous lymphadenitis

Even though we did not find any necrosis in this case, yet, it is worthwhile to review briefly the various causes of necrotizing lymphadenitis.

  • Non-suppurative

Tuberculosis: Histology of a tuberculous lymph node is characterised by central caseous necrosis surrounded by an epithelioid cell layer. The outermost layer is comprised of lymphocytes and fibrosis. Plasma cells are not observed. Diagnosis can be established by performing an AFB stain that demonstrates acid fast rod shaped bacteria in the areas of necrosis. Organisms can also be detected by PCR.

BCG lymphadenitis: About 0.7 to 2.3% of BCG vaccinated children may develop BCG lymphadenitis that is smaller than tuberculous lymphadenitis. Early phase shows follicular hyperplasia and sinus histiocytosis. Later, there is development of micronodules of epithelioid granulomas without necrosis and epithelioid cell granulomas with central caseous necrosis. Langhans giant cells are rare.

Fungal infections: Fungal infections by Histoplasma, Cryptococcus, coccidiodomycosis, pneumocystis may also cause a necrotizing granulomatous inflammation. There are numerous neutrophils, and fungal structures can be seen. GMS and PAS can be used in cases where it is difficult to the find the fungal elements on H&E.

  • Suppurative

Tularemia: There are three forms of histological changes, Abscess form, showing abscess with central necrosis and mononuclear cells, Abscess-granulomatous form with granulomas with central necrosis, which form large lesions with central abscesses, and granulomatous form with caseating necrosis at the centre of the granulomas.

Cat Scratch disease: Similar to tularemia, there are three phases of histologic presentation, an early phase of follicular hyperplasia, intermediate phase of microabscess, and a late phase of granulomatous inflammation. Monocytoid B cell clusters are observed close to the abscess.

Conclusion

Sarcoidosis is usually diagnosed by excluding other causes of granulomatous inflammation, as we did in this case. Characteristic non-necrotizing, discrete granulomas were seen throughout the lymph node. The age of the patient and female gender epidemiologically support the diagnosis. This case reflects an example work up of a granulomatous lymphadenitis that is a morphologic presentation of myriad diseases.

-Swati Bhardwaj, MD has a special interest in surgical pathology and hematopathology. Follow her on Twitter at @Bhardwaj_swat.

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

Global Health Narratives Interview Series: Meet Dr. Kumarasen Cooper.

Kumarasen Cooper, MD, PhD completed his medical training from his home country in South Africa and his PhD at Oxford. He now works as a surgical pathologist at the University of Pennsylvania and is responsible for leading the initiative to engage the pathology department in the Botswana-UPenn partnership through the Perelman School of Medicine Center for Global Health. He has over 260 publications and has lectured in 5 continents. Despite this busy schedule, Dr. Cooper devotes two separate months of the year to work in Botswana’s only academic pathology department, where he pours his energy into helping the department advance.

I met Dr. Cooper through email when I heard about the work he was doing in Africa. He generously agreed to come visit my department to give an excellent Grand Rounds lecture on his experiences working in Global Pathology, and he led a much-appreciated resident slide session of unusual and difficult cases from his work in Botswana. Humility and grace envelop Dr. Cooper despite his brilliant accomplishments. He also proved to be incredibly generous with a refusal of his speaker honorarium, in exchange for an agreement that we would collect pathology textbooks to send to the under-supplied residency program in Botswana. I’m excited to share the inspiring work that he does through the Botswana-UPenn partnership with all of you today, as I think this program could be used as a model for all institutes to involve their pathology departments in global health opportunities.

Q: What began your interest in global health?

A: I was born, raised, and completed my medical training in South Africa. I spent 15 years working as a Pathologist and served as the Chair of Pathology in Johannesburg until I was recruited to the US to work as Vice-Chair at the University of Vermont. I knew when I left Africa that I would always come back, and that I could use what I learned abroad to give back in some way. I wasn’t sure in what form that would take at the time, but I knew there was work that still needed to be done. This was also influenced by my visits to the pathology departments in many different countries over the years…I was able to gain a sense of the ‘haves and have-nots’, and so developed a strong feeling that I needed to give back.

Q: How did you hear about the Botswana-University of Pennsylvania (BUP) partnership and was pathology an active part in that already?

A: When I first discovered the partnership, I thought that this may be an avenue for me to participate in global pathology. At the time, the pathology department was not involved in any of the ongoing BUP projects, though other clinical departments at UPenn were. After my initial assessment of the Botswana pathology department and its resources in April of 2016, I was able to identify ways that I could help. Together with the Director of BUP, I approached the Chairman of my department with the proposal, and we started the pathology partnership program in October of that year. Since then, I travel to Botswana twice a year for one month at a time, and each time I take 1-2 residents from UPenn along with me.

Q: Can you describe the pathology department in Botswana?

A: To serve a population of just over 2 million people, Botswana has only one academic pathology department, a College of the University of Botswana (UB) School of Medicine, which consists of six pathologists who are all from other countries. There are currently no Botswana pathologists working in the department. There are about six technicians working in the laboratory, all of whom were trained internationally. The laboratory receives around 7,000 surgical specimens yearly, plus cytology, and autopsy. They work with an extremely limited panel of immunostains that are not routinely used but are spared for the rare case that cannot be diagnosed with morphology alone.

The residency program is still very new. There are six residents in the program at the present time, and the program is designed so that they will spend the first two years in Botswana and then they will continue their final years of training in South Africa. I look forward with anticipation to the first Botswana trained pathologists in the country.

Q: What is your role when visiting Botswana?

A: We try to help with everything we can. I sign out cases with the residents during the time I am there, and I teach the residents using these cases every day. The UPenn residents that I bring with me are eager to teach as well, so they deliver didactics regularly also. We all participate in tumor boards and the FNA clinic. We each take on projects that we can partner with them to tackle…things like improving turnaround time, quality improvement, and SOP preparations.  We also work on developing academic programs, grossing templates and manuals (A UPenn pathology PA spent two weeks working in Botswana on this project), synoptic reports, cancer guidelines…anything they need I try to help them with.

Q: How are the UPenn pathology residents given credit in their home program to join you?

A: As of this year, the BUP pathology program is now offered as one of the official electives that residents are allowed to choose from. They are able to use elective time and their travel expenses are paid for by a resident travel grant.

Q: In your role as supervisor of the UPenn residents, what do you see the residents gaining from the experience?

A: The residents that have come with me to Botswana are very compassionate and are eager to contribute in any way they can. Experiencing pathology in Botswana, where people are trying to achieve so much with so little resources, it makes the UPenn residents even more grateful for all of the resources they have available to them. They also have the opportunity to not only learn from the unusual cases that present in Botswana, but also the opportunity to contribute their own unique set of skills – some have focused on teaching autopsy technique, others give enthusiastic  and detailed lectures, and one gave a talk about successful study techniques. [For more information about the resident experience, one can read more about it in the UPenn blog here: https://pathology.med.upenn.edu/department/blogs/residency-matters/penns-pathology-residency-program-reaches-botswana]

Q: How do you see the BUP pathology partnership affecting the trainees in Botswana? What changes have you seen since you started working with them?

A: The residents in Botswana really appreciate the partnership that we have formed.  I have seen the residents develop so much since working with them. At first, they were reserved and now they actually request lectures on topics they feel they could improve on. They are still very humble and respectful, but I have encouraged them to be advocates for themselves. They have really embraced their program and I’m very proud of them. We have a deep appreciation for each other and are proud of what we have achieved together.

We’ve also started hosting Botswana residents at UPenn for a one month rotation so they have the opportunity to supplement their training even further. We fly them to the US, house them, and include them in our residency training program for the month. They have the opportunity to sit in on sign-outs, shadow grossing and autopsy, attend conferences, and be exposed to the advanced testing that we routinely perform in the US.

Q: How do you see the pathology partnership growing in years to come?A: I’m currently helping them find placements in South Africa or possibly partnering with private laboratories to help expose the residents to a greater diversity and volume of cases. As the program continues to grow, we look forward to seeing the fruits of the partnership for many years to come.


-Dana Razzano, MD is a Chief Resident in her third year in anatomic and clinical pathology at New York Medical College at Westchester Medical Center and will be starting her fellowship in Cytopathology at Yale University in 2020. She was a top 5 honoree in ASCP’s Forty Under 40 2018 and was named to The Pathologist’s Power List of 2018. Follow Dr. Razzano on twitter @Dr_DR_Cells.

Surgical Pathology Case Study: A 43 Year Old Female with a Lung Nodule Noted on Imaging Following Chest Congestion

Case History

The patient is a 43 year old woman who experienced chest congestion and presented to her local physicians office. A chest X-ray was ordered and demonstrated a lung abnormality. A follow-up CT scan confirmed a 1.9 cm smoothly marginated nodule in the upper lobe with no adenopathy and a normal liver and adrenal glands. The nodule was mildly hypermetabolic on PET scan. A bronchoscopy was performed, which was non-diagnostic. Two subsequent CT scans demonstrated no change in the size of the nodule. Overall, the patient feels well and denies cough, hemoptysis, dyspnea on exertion, and weight loss. Due to the suspicion of cancer, the patient has decided to undergo a lung lobectomy.

Diagnosis

Received in the Surgical Pathology lab for intraoperative consultation is a 30.0 x 7.2 x 2.2 cm lung lobectomy specimen. There is an attached 6.2 cm staple line, which is removed and the subjacent resection margin is inked blue. The entire pleural surface is inked black. The specimen is sectioned revealing a 2.1 x 1.7 x 1.0 cm white-tan, firm, round nodule that is 0.5 cm from the blue inked resection margin and 0.2 cm from the black inked pleural surface. The remainder of the specimen is composed of red-tan, spongy, grossly unremarkable lung parenchyma without nodules or other lesions. Photographs of the specimen are taken (Figure 1). A representative section of the nodule is submitted for frozen section and read out as “diagnosis deferred”. Representative sections of the specimen are submitted as follows:

A1FS:   Frozen section remnant

A2-A7:   Nodule, entirely submitted

A8-A10:   Grossly unremarkable lung parenchyma

Immunohistochemical stains show the epithelial cells in the lesion to be positive for CK7, TTF-1, and surfactant proteins A and B which supports these cells to be type 2 pneumocytes (all controls are appropriate). Based on the immunohistochemical stains and routine H&E slides, the case was signed out as a sclerosing pneumocytoma

Image 1. Gross presentation of the well-defined, round sclerosing pneumocytoma.

Discussion

Sclerosing pneumocytoma (SP) is a rare, benign pulmonary tumor that was first described in 1956 as a vascular tumor, but has since been found to be of primitive respiratory epithelium origin. In the past, SP has also been referred to as sclerosing hemangioma, pneumocytoma, and papillary pneumocytoma, but the 2015 World Health Organization classification of lung tumors states that the agreed upon term for this tumor should be a sclerosing pneumocytoma. SP is commonly seen in middle aged adults, with a female to male ratio of 5:1. There is no racial bias. Patients are usually asymptomatic, with the tumor incidentally found on screening chest radiographs. If the patient was to present with any symptoms, they would usually include a cough, hemoptysis and chest pain. Radiographically, SP appears as a solitary, well-defined, homogenous nodule along the periphery of the lung.

Grossly, most SPs appear as a solitary, firm, well-circumscribed, yellow-tan mass generally arising along the periphery of the lung. The majority of these tumors appear within the lung parenchyma, but there have been cases reported of endobronchial and pleural based SP tumors. Multifocal unilateral tumors and bilateral tumors are uncommon.

Histologically, SP consists of two epithelial cell types: surface cells and round cells. Surface cells are cuboidal, resembling type II pneumocytes, with finely stippled nuclear chromatin, indistinct nuclei, occasional nuclear grooves, and inclusions. The stromal round cells will have bland oval nuclei with coarse chromatin and eosinophilic cytoplasm (Figure 2). Both the surface cells and round cells will have a low mitotic rate, but can have moderate to marked nuclear atypia. Ciliated bronchial epithelium is often identified in the tumor. There are four architectural patterns identified within SP: papillary, sclerotic, solid and hemorrhagic, with over 90% of SPs displaying three of the patterns, and all of the tumors containing at least two of the patterns.

  • Papillary pattern: Complex papillae composed of surface cells covering a stroma of round cells
  • Sclerotic pattern: Papillae containing hyalinized collagen, either in solid areas or along the periphery of hemorrhagic areas (Figure 3)
  • Solid pattern: Sheets of round cells bordered by surface cells
  • Hemorrhagic pattern: Large blood filled spaces
Image 2. Photomicrograph demonstrating the cuboidal surface cells and round stromal cells.
Image 3. Photomicrograph of the papillary and sclerotic architectural patterns.

Immunohistochemical stains can be helpful in the diagnosis of SP, with both the surface cells and round cells exhibiting expression of thyroid transcription factor 1 (TTF-1) and epithelial membrane antigen (EMA). It should be noted that TTF-1 is also used for the diagnosis of pulmonary adenocarcinoma, increasing the risk of misdiagnosing SP. The surface cells will also express both pancytokeratin (AE1/AE3) and Napsin A, with the round cells being negative for AE1/AE3, but having a variable expression of cytokeratin 7 and the low molecular weight cytokeratin (CAM 5.2). Molecular pathology has demonstrated a frequent loss of heterozygosity at 5q, 10q and 9p, and an allelic loses at p16 in the surface and rounds cells. Although the immunohistochemical stains and molecular pathology results can be very helpful, diagnosis of a SP is still largely based on routine H&E slides showing the two epithelial cell types and four architectural patterns.

Electron microscopy will show abundant lamellar bodies similar to those in type II pneumocytes in the surface cells. Round cells will lack the lamellar bodies and instead will contain variably-sized electron-dense bodies that have been thought to represent the different stages of lamellar body maturation.

The differential diagnosis for SP includes a variety of benign and malignant neoplasms, which can be difficult to distinguish on cytology, small biopsies and intraoperative consultations. The cytologic features include moderate to high cellularity with a bloody background and foamy macrophages, occasional nuclear pleomorphism in the round cells, absent mitotic figures, and occasional necrosis with cholesterol clefts and calcifications. In the case of small biopsies, making a diagnosis of SP can be difficult if the papillary pattern is highly prevalent without one of the other three patterns present. With intraoperative consultations, the frozen section artifact can make it difficult to appreciate the two epithelial cell types or the four architectural patterns. The gross examination, as well as the radiographic findings of a well-circumscribed tumor can help point the Pathologist to favoring a benign neoplasm over a malignant one. The benign neoplasms that should be considered in the differential diagnosis include:

  • Clear cell tumor, which will have clear cells with scant stroma, thin-walled vessels and a strong expression of HMB-45
  • Pulmonary hamartoma, which will have a combination of cartilage, myxoid stroma, adipose tissue and trapped respiratory epithelium
  • Hemangiomas, which are rare in the lung, and will lack epithelial cells and contain either a cavernous or capillary morphology

The malignant neoplasms that should be considered in the differential diagnosis include:

  • Bronchioalveolar carcinoma, which can have a papillary pattern, but will not contain the two epithelial cell types and combination of the four architectural patterns
  • Metastatic papillary thyroid carcinoma, which is distinguished from SP by the presence of the characteristic Orphan Annie nuclei
  • Metastatic renal cell carcinoma, which will contain nuclear atypia and striking vascularity
  • Carcinoid, which will contain organoid and ribbon-like growth patterns

Currently, with the benign nature of SP, surgical excision is the preferred treatment choice to cure the patient. There have been cases reported of lymph node metastasis and recurrence, but neither of these appear to effect the prognosis. This just helps to highlight the need for a multidisciplinary approach to this benign tumor.

References

  1. Hisson E, Rao R. Pneumocytoma (sclerosing hemangioma), a Potential Pitfall. Diagn Cytopathol. 2017;45(8):744-749
  2. Keylock JB, Galvin JR, Franks TJ. Sclerosing Hemangioma of the Lung. Arch Pathol Lab Med. 2009;133(5):820-825.
  3. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 2015;10(9):1243-1260.
  4. Wu R. Sclerosing Pneumocytoma (Sclerosing Hemangioma). Pathology Outlines. http://www.pathologyoutlines.com/topic/lungtumorsclerosingheman.html. Revised February 19, 2019. Accessed June 6, 2019.

-Cory Nash is a board certified Pathologists’ Assistant, specializing in surgical and gross pathology. He currently works as a Pathologists’ Assistant at the University of Chicago Medical Center. His job involves the macroscopic examination, dissection and tissue submission of surgical specimens, ranging from biopsies to multi-organ resections. Cory has a special interest in head and neck pathology, as well as bone and soft tissue pathology. Cory can be followed on twitter at @iplaywithorgans.

Microbiology Case Study: A 58 Year Old Female with Abdominal Pain

Clinical History

A 58 year old female with no significant past medical history presented her primary care physician with chief complaint of abdominal pain. She reported continued vague abdominal symptoms for the past two months, with intermittent diarrhea and increased flatulence. No recent travel history or significant exposures were identified. An ultrasound of the right upper quadrant was unremarkable and no gallstones were present. The patient was scheduled for a screening colonoscopy. A stool specimen was submitted to the microbiology laboratory for stool culture and ova & parasite exam.  

Laboratory Identification

Image 1. Trichrome stained fecal smear illustrating a binucleated trophozoite with fragmented karyosomal material from a stool ova & parasite exam.
Image 2. Additional trichrome fecal smear image highlighting both uninucleate and binucleate trophozoites that range in size from 5 to 15 um.

The findings from the ova and parasite exam were consistent with Dientamoeba fragilis, an intestinal flagellate. The stool culture was negative for Salmonella, Shigella, and Escherichia coli 0157:H7. Stool enzyme immunoassays were negative for Campylobacter spp.and Shiga toxin 1 and 2.

Discussion

Dientamoeba fragilis is an intestinal flagellate with worldwide distribution and causes asymptomatic and symptomatic infections, predominantly in small children. Symptoms of infection may include intermittent diarrhea, abdominal pain, anorexia, weight loss, and flatulence.  While the pathogenesis is not completely understood, transmission is thought to occur via the fecal oral route and it is hypothesized that the trophozoites are transmitted via the eggs of nematodes, Enterobius vermicularis and Ascaris lumbricoides, due to a higher incidence of co-infections between these organisms than expected.

In the laboratory, the diagnosis of D. fragilis is made by ova and parasite exam. The trophozoite resembles amebae and is typically 9-12 µm. Most trophozoites are binucleate with finely granular cytoplasm and the within the nuclei there are 4-8 fragments of karyosomal granules (Figure 1). Due to the fact that 30-40% of D. fragilis trophozoites are uninucleate (Figure 2) and they lack external flagella, they must be differentiated from Endolimax nana and Entamoeba hartmanni, which are both non-pathogenic amebae. Historically, no cyst phase was known for D. fragilis; however, recent studies have identified precyst forms or putative cysts. Permanently trichrome stained slides are essential to diagnosing D. fragilis infection, as the organism is hard to detect in concentrated smears.

Since our patient was symptomatic, she was treated with iodoquinol, the drug of choice for D. fragilis infections. Her symptoms resolved and colonoscopy did not reveal additional pathology.  

-Debbie Walley, MD, is a 4th year Anatomic and Clinical Pathology chief resident at the University of Mississippi Medical Center. 

-Lisa Stempak, MD, is an Assistant Professor of Pathology at the University of Mississippi Medical Center in Jackson, MS. She is certified by the American Board of Pathology in Anatomic and Clinical Pathology as well as Medical Microbiology. She is the Director of Clinical Pathology as well as the Microbiology and Serology Laboratories. Her interests include infectious disease histology, process and quality improvement, and resident education.

Hey, What’s the Buzz on Zika?

Hello everyone and welcome back!

Last month, it was as fun to write about hematology peripheral smear differentials as it was to address the importance of interdisciplinary collaboration. I found myself in a unique position both as a medical student as well as a former medical laboratory scientist in what was a great clinical training rotation in hematology/oncology. Now, with just one rotation left until the end of my medical school journey, I want to take you on a look back at some of the very first posts I made here on Lablogatory and update you on the intersectional, collaborative topic that I shared with you almost two years ago: Zika!

Image 1. ASCP’s official professional society partner, The Pathologist. I’ve been getting them in my mailbox since the official partnership was announced. It’s an excellent platform for laboratory professionals across scopes to discuss relevant topics in pathology. I was particularly excited to see Zika make an appearance last month! (Source: The Pathologist [online] https://thepathologist.com/diagnostics/our-powers-combined)

In a recent digital article on ASCP’s partner, The Pathologist, author and staff editor Michael Schubert wrote about the connectivity between public health, epidemiologic research, laboratory medicine, and clinical patient outcomes. He examined the effectiveness and accuracy of Zika testing availability in commercially available assays and spoke with a leading virologist in the field from Berlin. You may recall one of those “ancient” posts I made about Zika, where I was part of a research team that used the same methodology! Combined immunoglobulin-specific assays, arbovirus detection in the heat of a public health epidemic’s epicenter, and lab medicine that complimented my concurrent immunology class in med school—what more could you ask for?

And, since the last tagged Lablogatory Zika update I can see was by Dr. Sarah Riley in February of 2017, here’s my update! Dr. Riley’s post was a fantastic summary of the Zika epidemic, its troublesome diagnostic assessments, and the recommendations and plans of organizations like the World Health Organization (WHO). She was, and still is, right—the “struggle is still real’ when it comes to Zika testing. Curious about what it was like during the 2016 epidemic? Who was doing testing, what kind of testing, and what was the lab data climate? Well…it feels like it’s time for a…

*** FLASHBACK ***

An Arbovirus Abroad

Hey! My inaugural post! It was fun to go back and see the data from the work then (Spoilers: epidemiologic updates are on your horizon). We were just getting started to take an assessment of the situation and address it as a public health concern. My then Caribbean location was a great place to study Zika trends coming from Brazil, Puerto Rico, and Florida. As a snapshot, at that time (Dec 2016) there were a purported almost 2,000 cases, however less than a fifth of those cases were serologically confirmed by lab testing. Before the recommendations to move toward RT-PCR, most labs in the region were requesting commercially available screening tests for IgG/IgM assays.

Image 2a. These were the (then) suspected Zika viral infection cases per epidemiological week, Pan-American Health Organization (PAHO) and World Health Organization (WHO) 2016. My wife and I are included in these statistics—that mosquito virus rash is awful!
Image 2b. Remember that spoiler I promised above? Well here’s the updated WHO epidemiologic data for confirmed Zika cases in the region we worked in. Seems like the mosquitoes…buzzed off. (Source: WHO)

Healthy Me

How do you reach people when you’ve got compelling public health lab data that translates to possible prevention of infection and spread of disease? Easy: go to where the people are and engage them when and where they’re comfortable. One of the overarching themes in public health is mitigating barriers to change by way of utilizing social humility. This a certainly a type of interdisciplinary collaboration because if we’re the experts on IgM and IgG trends in testing confirmations, the public are the experts in social determinants of health within their communities.

Image 3. Want to make sure a message gets home to every family? Bug their kids about Zika bugs in fun, educational ways. That’s me delivering one of my “Healthy Me” presentations to children, October 2016.

Laboratory Data and Global Health Security

As my team and I were busy preparing SOPs, conducting a new project aimed at improving local health literacy and source reduction, securing IRB approval, and collecting data about the residents of Sint Maarten to correlate with local Health Ministry projections, one of the officials—who now serves as a regional director for PAHO—took our work to the Global Health Security Agenda Summit. Talk about motivation! In and out of the lab, I worked with teams who were getting some fantastic work done on the ground with respect to mosquito-borne virus research.

Image 4. IgM and IgG seroprevalence of Zika virus (along with other Arboviruses i.e. West Nile, Chikungunya, Dengue, and Yellow Fever etc.) within the community around my medical school. We used commercially available IgG and IgM assays from Germany with great success. Internal controls and known cases were fantastic ways to include internal validation.

IRBs and Public Heath Pathology

For those of us who work in laboratory medicine, it’s easy to talk about the best way to test, detect, and treat an epidemiologic threat—it’s even exciting when it’s a current threat. But to really be successful, you’ve got to collaborate with those outside of the lab, and often this means thinking “outside the box.” Public health is different from lab medicine in that while lab-work is based around results, testing, and organized data-driven decisions, success in public health is highly determined by community buy-in in the form of partnerships!

Figure 1. There’s a method to the community “buy-in” concept. With a foundation in evidence-based practices, any project aimed at improving public health outcomes must include some critical components like clear objectives, attainable goals, sustainability, and effective (and constant) re-evaluation.

*** FLASH … FORWARD? ***

So, after my time in Sint Maarten, I came to New York City to rotate through my clinical clerkships. And, if you’ve seen some more recent post-Zika posts on this website, you know they’ve been going great! Within a few months of being here, my wife brought back some swag from a training session she attended. (Side note: she’s a graduate-level nurse, working in the public health non-profit sector with vulnerable populations in the inner city—she’s too busy to blog.) After months of both of us working and learning about Zika and public health initiatives in the Caribbean, we were greeted by this fantastic toolkit from the New York State Department of Public Health!

Image 5. Empowering a large number of patients with highly variable demographics is challenging. The NYS DOH distributed “Prevention Kits” for Zika Virus which included: Zika Virus educational materials in 8 languages, pamphlets on reducing mosquito activity, travel related information for pregnant women, 2 larvicide pellets with instructions for using larvicide, picaridin insect repellent, and condoms.
Image 6. That’s us! My wife Kathryn and I presenting on the importance of Disaster Planning and Implementation of Preparedness Programs at the 2019 Caribbean Conference of Disaster Medicine. Disasters are bad on their own, but think about what happens months after flooding, hurricanes, or destruction—transmittable diseases. And that includes standing-water-borne mosquito viruses!

The take home message: collaboration is key, both inside and out of the lab. Schubert’s piece in The Pathologist created a fantastic dialogue in addressing the clinical needs for interdisciplinary collaboration. The best testing means finding out exactly where the needs are and using data-driven decisions to implement change or action. In the lab, that means constantly working for higher quality and better patient outcomes in every test, result, report, and (mosquito) byte of data. In the field, it means the same thing, but instead of metrics like sensitivity, specificity, and TAT it’s about cultural humility, attainable goals, and dynamic timing.

Thanks for reading! Hope most of our national heat wave spared you, but if it didn’t remember: don’t keep standing water around, wear light loose clothing, and use appropriate insect repellent!

See you next time!

–Constantine E. Kanakis MSc, MLS (ASCP)CM graduated from Loyola University Chicago with a BS in Molecular Biology and Bioethics and then Rush University with an MS in Medical Laboratory Science. He is currently a medical student actively involved in public health and laboratory medicine, conducting clinicals at Bronx-Care Hospital Center in New York City.