2019 Research Forum

Jonathan Bowen MS IV, Leila Moosavi MD R3, Amit Sah MS IV, Arash Heidari MD, Everardo Cobos MD LEPTOMENINGEAL CARCINOMATOSIS FROM CARCINOMA OF UNKNOWN PRIMARY

Leptomeningeal metastases are a rare but frequently devastating complication of advanced cancer. The most common solid tumors giving rise to leptomeningeal metastases are breast, lung, melanoma and cancers of unknown primary. We are presenting a rare case of leptomeningeal metastases from carcinoma of unknown primary with increased intracranial pressure. Case Report

Introduction

Discussion ● Only 5% of cancers ever progress to leptomeningeal carcinoma (LMC). The most common solid tumors giving rise to LMC and their incidence rates are as follows; Breast: 12-35%,Lung: 10-26%, Melanoma: 5%, Colorectal 1%. Gastro-Intestinal cancer as far as we have discovered is an extremely rare cause of LMC outside of Asian populations. ● Life expectancy from the time of diagnosis of LMC to demise is 2-4 months even with treatment. Making this not only a very tragic diagnosis but incredibly difficult to study and research new treatments on. ● CDX-2 is a tumor marker when positive is supportive of and commonly found on gastro- intestinal cancers. In our patients case however no gastric, Intestinal, or anything suspicious of a gastro- intestinal primary mass was found despite numerous imaging studies. ● Rapid diagnosis of LMC is challenging as it can present with a wide range of non-specific symptoms from headache to focal neurological deficits and can involve multiple areas of the craniospinal axis. Conclusions ● Leptomeningeal Carcinomatosis has an extremely poor prognosis without an accepted standardized approach or treatment protocol. ● Although newer targeted and immunotherapeutic agents are currently under investigation and have shown promise, an improved understanding of the biology of leptomeningeal metastasis and treatment as well as additional randomized trials are needed to guide optimal treatment of this devastating disease. References ● Leptomeningeal metastasis from systemic cancer: review and update on management; Wang N, Bertalan MS, Brastianos P. ● Leptomeningeal metastases of solid cancer Le Rhun E, Galanis E. ● Immunohistochemistry for diagnosis of metastatic carcinoma of unknown primary site; Janick Selves, Elodie Long-Mira, Marie-Christine Mathie, P Rochaix. ACKNOWLEDGEMENT We would like to thank the patient, Dr. William Stull, the KMC pathology department and KMC Radiology Department for their contributions to this case.

Four months after initial presentation and having received total 3 cycles of Carplatin and 2 cycles of Taxotere, patient was admitted for one week history of headache described as worst headache of her life. MRV/ MRI were remarkable for slight narrowing of the distal portion of the straight sinus and leptomeningeal enhancement but negative for hydrocephalus (Figure 3).

A 32 year old Hispanic Female with no significant past medical history initially presented at another hospital with a two month history of dry cough, pleuritic chest pain and unintentional weight loss. Labs were significant for microcytic anemia Hgb: 8.0, hematocrit : 25, MCV: 66, WBC and Platelets were within normal limits. Patient underwent CT chest, abdomen & pelvis at different facility that showed abnormal mediastinal (Figure 1a and 1b) and retroperitoneal adenopathy and a 3.3cm cystic ovarian mass.

Patient’s headache was relieved initially by lumbar punctures (LP) which had elevated opening pressures. She received serial of LPs for symptomatic relief and diagnostic work-ups (Figure 4). Complete infectious cerebral spinal fluid workup was ordered ( Figure 5). Intrathecal cytarabine was initiated after malignant cells (Figure 6) were seen in CSF.

Figure 3: CT brain w/contrast no mass effect and no hydrocephalus.

Figure 4: Serial Diagnostic and Therapeutic Lumbar Punctures.

Figure 5: CSF infectious work up

Figure 6: CSF PAP 40X showing malignant cell.

Figure 1b: CT with contrast showing right paratracheal node that is 45 x 25mm.

She continued to deteriorate and develops photophobia with loss of peripheral vision despite intrathecal chemotherapy. In attempt to find primary source, patient underwent Cervical lymph node (Figure 7) biopsy with additional IHC stains (Figure 8).

Figure 1a : CT with contrast showing carinal and hilar adenopathy.

Biopsy of right mediastinal lymph node was sent for immunohistochemical staining (IHS) which was remarkable for weakly positive Placental Alkaline Phosphate (PLAP) and strongly positive pan-keratin (AE1 and AE3) suggesting adenocarcinoma with possible ovarian primary. Patient was started on chemotherapy outpatient. Additional tumor markers were pending and due to her rapidly progressing symptoms systemic chemotherapy of Carplatin and Taxol Q 3 weekly was started. Patient had allergic reaction to initial dose of Taxol and it was replaced with Taxotere. Nine days after induction of first chemotherapy cycle, she presented to ED with new symptoms of neck pain with swelling; CT neck revealed SVC syndrome with a significant thrombus in right internal jugular (Figure 2) that was extending to superior mediastinum and patient was started on Xarelto.

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Figure 8: Immunohistochemistry stains of Cervical lymph node biopsy: (A) H and E, 4X showing malignant cells infiltrating subcapsular sinus and spread throughout the sinusoids. (B) CK 7 positive , 10X: Seen in Lung, breast and upper Gastro-Intestinal adenocarcinoma type malignancies.

Figure 7: CT with contrast showing right cervical lymph node measuring 15 x 13mm.

(C) CDX 2 positive, 10X: Seen in Gastro-Intestinal primary malignancies. (D) PLAP positive, 10X: Non-specific, typically associated with germ cell tumor. (E) TTF 1 NEGATIVE, 10X: Seen in thyroid and lung malignancies.

After receiving four cycles of intrathecal cytarabine , one dose of intrathecal methotrexate, and three cycles of Carboplatin + Taxotere. Patient appeared to be severely deconditioned and continued to have declining performance. Oncology determined she was a poor candidate to receive additional chemotherapy as well as developed a hematoma at the serial LP site which when combined with severe leptomeningeal disease confers a poor prognosis (Figure 9). After five months of fighting her cancer, she refused intraventricular shunt, additional procedures, and treatment. Patient and her family proceeded with comfort care measures and hospice.

Figure 9: CT brain w/o Contrast showing increased right parafalcine hyperdensity infiltrating the extra axial last space from cranial vertex to lower centrum semiovale where there is obliteration of sulci. Extends over AP diameter of 7.1cm and width of 1.6cm. It corresponds to leptomeningeal carcinomatosis. However, no midline shift or hydrocephalus or herniation syndrome appreciated.

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Figure 2: CT neck soft tissue with contrast (A) Sagittal view showing thrombus with filling defect in Right Internal Jugular vein (IJV). (B) Coronal view showing thrombus in right IJV with normal Left IJV. (C) Sagittal view showing no thrombus in left IJV.

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